Potentiation of anti-obesity activity of berberine through its encapsulation in guar-acacia gum nanocomplexes in Wistar albino rats

Potentiation of anti-obesity activity of berberine through its encapsulation in guar-acacia gum nanocomplexes in Wistar albino rats | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Potentiation of anti-obesity activity of berberine through its encapsulation in guar-acacia gum nanocomplexes in Wistar albino rats Jyoti Bakshi, Prity Lathar, Assim Verma, Deepika Lather, Sapna Grewal, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3928032/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Berberine is a promising bioactive compound that has gained great attention against numerous diseases but its low solubility and poor systemic bioavailability hinders its clinical applicability. Therefore, this study attempted to enhance the therapeutic potential of berberine by its nanoencapsulation. Berberine loaded guar-acacia gum nanocomplexes (Ber/Gu-AGNCs) were prepared by ionic complexation method; characterized and evaluated for anti-obesity activity in high fat diet (HFD) induced obese rats. HFD was given to animals for 6 consecutive weeks. Orlistat (20 mg/kg, p.o.), berberine (10 mg/kg), Ber/Gu-AGNCs (10 and 20 mg/kg, p.o) and Gu-AGNCs (blank) were administered once a day after giving HFD for 6 weeks; and continued up to 12 weeks along with HFD. Obesity was evaluated by the measurement of morphological parameters, blood glucose, serum lipid profiles, liver enzymes and levels of oxidative stress markers. Moreover, histopathological studies of liver and adipose tissue were also carried out. The results showed that Ber/Gu-AGNCs exhibited spherical morphology and narrow size distribution. In addition, Ber/Gu-AGNCs were significantly more effective in controlling the body weight, BMI, adiposity index, liver index, blood glucose levels, serum lipids and oxidative stress levels in comparison to berberine in HFD-induced obese rats. Furthermore, histopathological examination of liver and adipose tissue revealed the anti-obesity effect of Ber/Gu-AGNCs (10 and 20 mg/kg), as indicated by decrease in hepatosteatosis and inflammation in liver tissue; and decrease in the size of adipocytes in fat depots. Thus, nanoencapsulation of berberine into gum nanocomplexes displayed better anti-obesity activity when compared to free berberine. Berberine Nanoencapsulation High fat diet Anti-obesity Guar gum Gum acacia Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Obesity is a common health disorder described by a severe buildup of high proportion of body fat in adipose tissues and hence resulted in an increase in body weight [ 1 ]. The changing life style, lack of exercise, high calorie food, genetic background, etc are some of the factors that causes imbalance between the intake and expenditure of energy, thereby leading to the development of obesity [ 2 ]. The prevalence of obesity has increased globally over the past decades cutting across age groups, ethnicity and sex; and turned to be the major contributor for the development of various diseases such as type 2 diabetes, cardiovascular disorders, hypertension and certain cancers [ 3 ]. Although few FDA approved synthetic drugs like orlistat and sibutramine show remarkable effect in the management of obesity, but these are not preferred for long term usage due to their side effects such as headache, constipation, weight rebound on discontinuation, etc [ 4 ]. Therefore, there is an ever-pressing need for developing safer and effective anti-obesity medicines from natural sources. Berberine is a natural plant alkaloid, derived from many plants like Berberis aristata , Coptis chinensis , Hydrastis canadensis , etc [ 5 ]. Berberine showed protective effect against type- 2 diabetes and hyperlipidemia in patients [ 6 , 7 ]. Berberine has various pharmacological properties in laboratory animals such as anti-inflammatory [ 8 ], antioxidant [ 9 ], anti-obesity[ 10 ], etc. However, despite its promising multi-spectrum pharmacological activities, berberine has been reported for its low bioavailability after oral administration due to its poor solubility and gastrointestinal absorption. To overcome these limitations, encapsulating drugs in a suitable nanocarrier can be considered. Some pre-clinical studies have suggested the improved therapeutic potential of berberine via polymeric nanoencapsulation [ 11 , 12 ]. The cationic nature of berberine displays a favorable possibility of its interaction with many polymeric carriers. Various polymers have been used for the development of berberine-containing nanoparticles including chitosan [ 13 ], chitosan-alginate [ 14 ], fucose-chitosan/heparin [ 15 ], and polycaprolactone [ 16 ], etc. In vivo studies showed improved bioavailability of berberine when loaded in chitosan-coated alginate/gelatin microspheres [ 17 ]. But nowadays the use of natural gums as excipients has increased in the pharmaceutical industry due to their sustained drug releasing effect [ 18 ] and enhancement of bioavailability of the bioactive compounds [ 19 ]. Guar gum is a non-ionic heteropolysaccharide, and obtained from the plant Cyamopsis tetragonoloba [ 20 ]. Guar gum possesses fascinating features desirable for drug delivery such as good stability [ 21 ] and excellent drug retarding properties [ 22 ]. Besides these, there is protective role of guar gum in high fat diet-induced obesity in rats [ 23 ]. Another extensively used anionic heteropolysaccharide obtained from Acacia senegal and Acacia seyal trees is gum acacia [ 24 ]. Owning to its outstanding safety profile, biocompatibility and biodegradability, gum acacia has achieved greater attention in the pharmaceutical industry [ 25 ]. Gum acacia has been reported to show protective effect against high fat diet-induced obesity in mice [ 26 ]. Additionally, gum acacia has been widely used for improving encapsulation efficiency [ 27 ] and bioavailability of the encapsulated drug [ 28 ]. In view of the above mentioned interesting properties of gum acacia and guar gum, this study was designed to evaluate potentiating effect of encapsulation of berberine in guar-acacia gum nanocarriers against HFD-induced obesity in rats. Till now, there are no reports in the literature on improved anti-obesity activity of berberine loaded guar-acacia gum nanocomplexes. Materials and Methods Drugs and Chemicals Berberine HCl was obtained from MP Biomedicals Pvt. Ltd. (Mumbai, India). Pure cholesterol, cholic acid, Tween 20, gum acacia powder, guar gum powder, glutaraldehyde, Ellman’s reagent (5,5’-dithiobis-(2-nitrobenzoic acid), EDTA, potassium chloride, mannitol and sodium lauryl sulfate were supplied by Hi-Media Lab. Pvt. Ltd. (Mumbai, India). Orlistat, n-butanol, acetic acid, trichloroacetic acid, thiobarbituric acid, pyridine and hydrogen peroxide were brought from Sigma-Aldrich, St. Louis (USA). Sodium dihydrogen phosphate (NaH 2 PO 4 ) and di-sodium hydrogen phosphate (Na 2 HPO 4 ) were obtained from SISCO Research Laboratories Pvt. Ltd. (Mumbai, India). Total protein, Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, Serum glutamic pyruvic transaminase (SGPT) and SGOT (serum glutamic oxaloacetic transaminase) were determined using kits (Erba, Transasia Bio-Medicals Ltd. Solan, India). Lard was purchased from slaughter house. Experimental Animals Wistar albino female rats (body weight 130–140 g; 4–6 months old) were procured from Experimental Animal Facility, Guru Jambheshwar University of Science and Technology, Hisar (Haryana, India). The number of animals use in this research study and experimental protocol were approved by Institutional Animal Ethics Committee (IAEC) in its meeting held on 10th Feb., 2022 [IAEC minutes letter No. IAEC/2022/10–18, dated 22-2-2022]. All the animals were housed in polypropylene cages (43 × 27 × 15 cm) and were maintained under standard laboratory conditions i.e., 12-h light/12-h dark cycle, temperature 24 ± 2°C for at least 5 days before the start of experiments. Food and water were given ad libitum to the animals. Preparation and characterization of Ber/Gu-AGNCs Ber/Gu-AGNCs were synthesized via the ionic complexation method using guar gum and gum acacia as polymers and Tween 20 as surfactant; and characterized by dynamic light scattering, FTIR and TEM. The details were given in our previous study [ 29 ]. Similarly, blank (Gu-AGNCs) was prepared consisting of guar gum and gum acacia but without berberine. Evaluation of in vivo Anti-obesity activity of Ber/Gu-AGNCs High fat diet-induced obesity Experimental obesity was induced in rats by feeding high fat diet (HFD) for a period of twelve weeks consisting of normal feed containing lard (10% w/w), pure cholesterol (2% w/w) and cholic acid (0.25% w/w) [ 30 ]. Diet was freshly prepared each day. Orlistat was dissolved in 1% v/v dimethyl sulfoxide in distilled water. Berberine was suspended in phosphate buffer (pH 7.4, 0.02 M) just before administration to the animals. The volume of oral administration of drug solution/vehicle was 1 ml /100 g body weight. Experimental protocol A total of 42 rats were used in the present study. Animals were categorized into following groups (n = 6 rats each): Group I (Normal control): Rats were fed with normal diet for twelve weeks. Group II (HFD control): Rats were maintained on HFD for twelve weeks to induce obesity. Group III (Orlistat, 20 mg/kg, p.o.): Rats were maintained on HFD for 6 successive weeks. From the end of sixth weeks to the end of twelve weeks, orlistat was given orally 1 h before feeding the animals with HFD. Group IV (Berberine, 10 mg/kg, p.o.): Rats were maintained on HFD for 6 successive weeks. From the end of sixth weeks to the end of twelve weeks, berberine was given orally 1 h before feeding the animals with HFD. Groups V and VI (Ber/Gu-AGNCs, 10 and 20 mg/kg respectively, p.o.): Rats were maintained on HFD for 6 successive weeks. From the end of sixth weeks to the end of 12 weeks, Ber/Gu-AGNCs were given orally 1 h before feeding the animals with HFD. Group VII (Gu-AGNCs, p.o.) - Rats were administered HFD for 6 successive weeks. From the end of sixth weeks to the end of 12 weeks, Gu-AGNCs were given orally 1 h before feeding the animals with HFD. Collection of blood samples; and Isolation of liver and adipose tissue At the end of 12 weeks, all the animals were sacrificed under anesthesia with chloroform and carbon dioxide. Blood samples (1 to 1.5 ml) were collected by carotid artery bleeding into sterilized centrifuge tubes. A small amount of blood was used for glucose estimation. The remaining blood was left for coagulation for 30 min and serum was collected by centrifugation at 3000 rpm at 4°C for 10 min using a refrigerated centrifuge (C-24Plus, RemiElektrotechnik Ltd., Maharashtra). The serum was stored at − 20° C for 1–2 days and then used for biochemical estimations. Liver and adipose tissues (retroperitoneal and mesenteric) were removed from all the rats, then washed in cold physiological saline and weighed. The tissue samples were stored at − 20° C for 1–2 days. Oxidative stress parameters were measured in liver homogenate of five rats of each group. Histopathological studies on liver and adipose tissue (retroperitoneal of one rat from each group) were carried out. Measurement of body mass index (BMI), waist circumference (WC), liver index and adiposity index The body weights of animals of all the groups were measured once in a week. Length of each rat was measured from its nose to anus. Waist circumference was measured on the largest zone of rat abdomen. Liver and adipose tissues (retroperitoneal and mesenteric) of rats were dissected out, rinsed with ice-cold phosphate-buffered saline (PBS, pH 7.4), and then weighed. BMI [ 31 ], adiposity index and liver index [ 32 ] were calculated according to the following formulae: BMI = \(\frac{\text{Body weight (g)}}{{\text{length}}^{\text{2}}\text{ (}{\text{cm}}^{\text{2}}\text{)}}\) Adiposity index (%)= \(\frac{\text{ Retroperitoneal, mesenteric fat}}{\text{body weight}}\times 100\) Liver index (%) = \(\frac{\text{liver weight}}{\text{body weight}}\times 100\) Estimation of blood glucose levels Blood glucose level was estimated using glucometer (BG-03 Model, Dr. Morepen Laboratories Ltd., Himachal Pradesh, India). Biochemical estimation in serum Estimation of lipid profile and liver enzymes The changes in lipid parameters like total cholesterol, triglycerides (TG), high density lipoprotein, SGOT and SGPT in serum samples were measured using biochemical kits as per the manufacturer’s instructions. Very low-density lipoprotein (VLDL) and low-density lipoprotein cholesterol (LDL) were measured indirectly according to the Friedewald formula [ 33 ]: VLDL = TG/5 LDL = TC- (HDL + VLDL) The atherogenic index was calculated using the following formula [ 34 ]: Atherogenic index (AI) = TC/HD Biochemical estimations in liver homogenate Protein content Total protein content in tissue homogenate was estimated using commercial kit with bovine serum albumin as standard. Estimation of Reduced glutathione (GSH) levels The levels of reduced glutathione in tissue homogenate were measured according to the procedure described in the previous study [ 35 ]. Briefly, 200 mg of liver tissue was homogenized in 8.0 ml of EDTA (0.02 M) in a homogenizer. To 5.0 ml of prepared homogenates, around 4 ml of distilled water and 1 ml of 50% trichloroacetic acid was added. The mixture was centrifuged at 3000 rpm for 15 min and supernatant was separated. To the obtained supernatant (approx. 2 ml), 4.0 ml of Tris buffer (0.4 M pH 8.9), and 0.1 ml of Ellman’s reagent (5, 5’-dithiobis-(2-nitrobenzoic acid) was added. The samples were mixed gently and absorbance was measured at 412 nm against reagent blank (without homogenate) using UV-Vis spectrophotometer (Genetix Biotech Asia Pvt. Ltd., New Delhi). Results were measured using the molar extinction coefficient of chromophore (1.34 × 10 4 M -1 cm -1 ) and expressed as nmol of GSH per mg of protein. Estimation of Catalase Catalase activity was measured according to the procedure as described earlier [ 36 ]. 5% liver homogenate was prepared in ice-cold 50 mM phosphate buffer (pH 7.0) using a homogenizer. The homogenates were centrifuged at 10,000 rpm for 20 min at 4°C. About 50 µl of supernatant was added to a solution containing 2 ml of phosphate buffer (pH 7.0) and 1 ml of 30 mM hydrogen peroxide. Catalase activity was measured spectrophotometrically at 240 nm and expressed as nmole of H 2 O 2 utilized/minute/mg of protein. Estimation of Malondialdehyde level (MDA) Malondialdehyde level was measured according the procedure as reported by Ohkawa et al [ 37 ]. Liver tissue (100 mg) was homogenized in 9.0 ml of 1.15% KCl by using a homogenizer. 0.2 ml of liver homogenate was added to reaction mixture consisted of 0.2 ml of 8.1% sodium lauryl sulphate, 1.5 ml of 20% acetic acid (pH 3.5) and 1.8 ml of 0.8% w/v aqueous solution of thiobarbituric acid. The total volume was made to 4 ml with distilled water and mixture was heated at 95° C for 60 min using a water bath. After cooling, 5 ml mixture of n-butanol and pyridine (15:1 v/v) and 1 ml of distilled water were added. The mixture was centrifuged at 4000 rpm for 10 min and upper organic layer was separated out. The absorbance of the upper layer was measured at 532 nm using UV-Vis spectrophotometer against a reagent blank. MDA concentration was calculated using extinction coefficient 1.56 × 10 5 M -1 cm -1 and expressed as nmol/mg of protein. Histopathological analysis The histological features of adipose tissue and liver tissue from one rat of each experimental group were studied. Adipose and liver tissues were collected, washed in phosphate buffer and fixed in 10% v/v phosphate buffered formalin for 48 h. Formalin-fixed tissues were processed using different grades of ethanol (70%, 80%, 90% and 100%) and xylene followed by embedding in paraffin wax. Further sections of paraffin blocks of 4–5 µm thicknesses were cut using rotary microtome (HistoCoreMulticut Semi-Automated rotary Microtome, Leica Biosystems, Mumbai, India) which were then stained with hematoxylin and eosin dyes [ 38 ]. The stained tissues slides were examined at 200x magnification and pictured using a microscope (Olympus, CX41, Tokyo, Japan) to study histopathological alterations. Statistical analysis The data were represented as mean ± standard error of mean (SEM). The results were statistically analyzed by one-way ANOVA succeeded by Tukey multiple comparison test using GraphPad Prism v 5.01 software. Data having p < 0.05 were considered to be statistically significant. Results and Discussion Synthesis and characterization of Ber/Gu-AGNCs The suspension of Ber/Gu-AGNCs was yellowish in color and odorless. The optimal calculated parameters were found to be a concentration of guar gum − 0.191 (% w/v), gum acacia − 0.271 (% w/v) and Tween 20–2.66% as discussed in our previous study [ 29 ]. The particle size, PDI, zeta potential and entrapment efficiency of the optimized batch of Ber/Gu-AGNCs were found to be 290.2 nm, 0.230, − 26.8 mV and 96.5%, respectively. A detailed explanation of the FTIR spectroscopy of Ber/Gu-AGNCs is given in our previous study. The data confirmed the successful encapsulation of berberine into the gum nanocomplexes without any unfavorable interaction between polymer and drug. TEM and SEM results showed spherical shaped nanocomplexes with size in the range of 100–250 nm. In vitro drug release of Ber/Gu-AGNCs In vitro drug release study showed that Ber/Gu-AGNCs have a sustained release behavior with 77.6 ± 1.7% of release in 48 h in contrast to their free forms. Effect of Ber/Gu-AGNCs on High Fat Diet-induced Obese Rats Effect of Ber/Gu-AGNCs on body weight, waist circumference (WC) and body mass index (BMI) HFD significantly increased body weight (p < 0.01), WC (p < 0.05) and BMI (p < 0.05) of rats at 1st week of its administration and this increase continued up to the 12th week (p < 0.001). These results are substantiated by a previous study [ 39 ]. The obese rats treated with standard drug (orlistat), berberine (10 mg/kg), Ber/Gu-AGNCs (10 and 20 mg/kg) and Gu-AGNCs (blank) once daily for 6 weeks (from 6th to 12th week) significantly decreased body weight (p < 0.001, p < 0.05, p < 0.001, p < 0.001, p < 0.001, respectively) and WC (p < 0.01, p < 0.01, p < 0.01, p < 0.05, p < 0.05, respectively) from 7th week onwards in comparison to HFD control rats. Orlistat, berberine (10 mg/kg) and Ber/Gu-AGNCs (10 and 20 mg/kg) also significantly decreased BMI (p < 0.001, p < 0.05, p < 0.001, p < 0.001, respectively) of obese rats from 7th week onwards in contrast to HFD control rats. However, Gu-AGNCs did not show a significant effect on BMI of rats at 7th and 8th week of their administration. Gu-AGNCs significantly decreased BMI of obese rats from the 9th week onwards as compared to HFD control rats. Moreover, Ber/Gu-AGNCs (10 and 20 mg/kg) displayed a significant decrease in body weight and BMI of obese rats in comparison to rats treated with Gu-AGNCs, indicating a better effect of Ber/Gu-AGNCs than Gu-AGNCs. In addition, 10 mg/kg dose of Ber/Gu-AGNCs also showed a significant decrease in body weight and BMI of obese rats in comparison to obese rats treated with free berberine (10 mg/kg). Ber/Gu-AGNCs did not show a significant decrease in WC in comparison to free berberine and Gu-AGNCs (Tables 1 , 2 and 3 ). The decrease in body weight by berberine is also substantiated by an earlier study [ 40 ]. Effect of orlistat in decreasing body weight, WC and BMI is consistent with a reported study [ 41 ]. The effect of guar gum and gum acacia in decreasing body weight in high fat diet-fed obese rats has been revealed in an earlier study [ 42 , 43 ]. Thereby, Ber/Gu-AGNCs showed better effects in decreasing body weight, WC and BMI than free berberine and Gu-AGNCs. Table 1 Effect of Ber/Gu-AGNCs on body weight of HFD-induced obese rats Body weight (g) Weeks NC HFD HFD + Orlistat (20 mg/kg) HFD + Ber (10 mg/kg) HFD + Ber/Gu-AGNCs (10 mg/kg) HFD + Ber/Gu-AGNCs (20 mg/kg) HFD + Gu-AGNCs 0 130.7 ± 0.81 131.96 ± 0.97 131.94 ± 1.30 130.52 ± 0.63 131.78 ± 0.46 129.00 ± 0.77 130.75 ± 0.63 1 131.95 ± 0.57 137.18 ± 0.86 aa 137.19 ± 1.18 136.91 ± 1.0 136.16 ± 0.89 136.58 ± 0.63 137.15 ± 0.85 2 133.72 ± 0.88 145.70 ± 1.74 aaa 146.52 ± 1.10 146.30 ± 1.89 146.94 ± 0.69 146.75 ± 1.58 145.53 ± 1.22 3 135.95 ± 0.59 154.98 ± 1.27 aaa 154.19 ± 1.08 153.64 ± 1.05 153.25 ± 1.11 154.36 ± 1.08 154.43 ± 1.28 4 135.85 ± 0.89 166.01 ± 1.87 aaa 166.62 ± 0.78 166.13 ± 1.65 166.97 ± 1.58 167.64 ± 0.60 167.45 ± 0.80 5 138.48 ± 0.70 177.64 ± 0.98 aaa 177.69 ± 1.32 177.45 ± 1.6 177.27 ± 1.88 178.62 ± 0.70 177.52 ± 0.69 6 142.77 ± 1.44 189.35 ± 1.09 aaa 189.89 ± 0.41 189.81 ± 0.50 189.67 ± 1.42 189.14 ± 0.80 189.15 ± 1.54 7 148.16 ± 0.58 202.44 ± 1.28 aaa 193.27 ± 1.12 bbb 198.92 ± 0.39 b 195.13 ± 0.26 bbb***# 194.12 ± 0.65 bbb*** 200.93 ± 0.17 bbb 8 152.82 ± 0.55 210.92 ± 1.08 aaa 198.93 ± 0.82 bbb 203.09 ± 0.03 bbb 200.29 ± 0.14 bbb***# 198.05 ± 0.34 bbb*** 206.37 ± 0.67 bbb 9 157.43 ± 0.83 223.93 ± 1.37 aaa 202.32 ± 1.08 bbb 213.4 ± 0.20 bbb 208.73 ± 0.18 bbb***# 205.00 ± 1.41 bbb*** 216.21 ± 0.64 bbb 10 162.64 ± 0.78 234.10 ± 1.08 aaa 206.04 ± 0.66 bbb 222.31 ± 0.68 bbb 215.22 ± 0.6 bbb***### 212.63 ± 1.32 bbb*** 225.59 ± 1.15 bbb 11 168.83 ± 1.23 245.28 ± 1.17 aaa 213.14 ± 1.57 bbb 229.76 ± 0.43 bbb 224.56 ± 0.28 bbb***# 218.58 ± 0.81 bbb*** 235.60 ± 0.90 bbb 12 172.05 ± 0.35 254.14 ± 0.41 aaa 216.88 ± 1.24 bbb 237.61 ± 0.30 bbb 230.76 ± 0.23 bbb***### 224.61 ± 0.94 bbb*** 243.10 ± 0.02 bbb Values are represented as mean ± SEM. Data were analyzed by one-way ANOVA followed by Tukey’s multiple comparison test (n = 6 each group). aa p < 0.01, aaa p < 0.001 vs. NC group; bbb p < 0.001 vs. HFD group; ***p < 0.001 vs. HFD + Gu-AGNCs, # p < 0.05, ### p < 0.001 vs. HFD + berberine NC: Normal control, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes, HFD: High fat diet Table 2 Effect of Ber/Gu-AGNCs on Waist circumference (WC) of HFD-induced obese rats WC (cm) Weeks NC HFD HFD + Orlistat (20 mg/kg) HFD + Berberine (10 mg/kg) HFD + Ber/Gu-AGNCs (10 mg/kg) HFD + Ber/Gu-AGNCs (20 mg/kg) HFD + Gu-AGNCs 0 11.42 ± 0.11 11.51 ± 0.14 11.51 ± 0.22 11.51 ± 0.22 11.55 ± 0.25 11.51 ± 0.19 11.55 ± 0.14 1 11.47 ± 0.10 12.01 ± 0.05 a 12.02 ± 0.12 12.02 ± 0.10 12.06 ± 0.14 12.02 ± 0.12 12.05 ± 0.12 2 11.84 ± 0.08 12.74 ± 0.10 aaa 12.74 ± 0.07 12.70 ± 0.09 12.78 ± 0.12 12.78 ± 0.08 12.78 ± 0.05 3 12.46 ± 0.11 13.54 ± 0.22 aaa 13.58 ± 0.14 13.50 ± 0.04 13.58 ± 0.17 13.63 ± 0.14 13.58 ± 0.21 4 12.87 ± 0.08 13.88 ± 0.08 a 13.92 ± 0.04 13.80 ± 0.10 13.88 ± 0.40 13.97 ± 0.13 13.88 ± 0.24 5 13.33 ± 0.12 14.94 ± 0.15 aaa 14.98 ± 0.06 14.85 ± 0.12 14.94 ± 0.16 15.02 ± 0.16 14.94 ± 0.12 6 13.84 ± 0.12 15.28 ± 0.19 aaa 15.32 ± 0.05 15.15 ± 0.08 15.24 ± 0.17 15.32 ± 0.17 15.28 ± 0.04 7 14.39 ± 0.10 16.46 ± 0.15 aaa 15.74 ± 0.11 bb 15.74 ± 0.09 bb 15.79 ± 0.07 bb 15.83 ± 0.10 b 15.91 ± 0.10 b 8 14.98 ± 0.16 17.37 ± 0.21 aaa 16.34 ± 0.05 bbb 16.51 ± 0.09 bbb 16.46 ± 0.07 bbb 16.46 ± 0.04 bbb 16.72 ± 0.04 bbb 9 15.62 ± 0.08 18.16 ± 0.05 aaa 16.77 ± 0.22 bbb 17.14 ± 0.05 bbb 17.01 ± 0.06 bbb 16.97 ± 0.04 bbb 17.43 ± 0.05 bbb 10 16.25 ± 0.09 19.47 ± 0.15 aaa 17.82 ± 0.19 bbb 18.36 ± 0.12 bbb 18.20 ± 0.05 bbb 18.07 ± 0.16 bbb 18.71 ± 0.21 b 11 16.93 ± 0.05 20.15 ± 0.08 aaa 18.07 ± 0.04 bbb 18.83 ± 0.04 bbb 18.62 ± 0.15 bbb 18.41 ± 0.18 bbb 19.21 ± 0.10 bbb 12 17.64 ± 0.11 21.46 ± 0.05 aaa 19.09 ± 0.04 bbb 20.02 ± 0.04 bbb 19.76 ± 0.10 bbb 19.51 ± 0.07 bbb 20.44 ± 0.12 bbb Values are represented as mean ± SEM. Data were analyzed by one-way ANOVA followed by Tukey’s multiple comparison test (n = 6 each group). a p < 0.05, aaa p < 0.001 vs. NC group; b p < 0.05, bb p < 0.05, bbb p < 0.001 vs. HFD group NC: Normal control, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes, HFD: High fat diet Table 3 Effect of Ber/Gu-AGNCs on BMI in HFD-induced obese rats BMI (g/cm 2 ) Weeks NC HFD HFD + Orlistat (20 mg/kg) HFD + Berberine (10 mg/kg) HFD + Ber/Gu-AGNCs (10 mg/kg) HFD + Ber/Gu-AGNCs (20 mg/kg) HFD + Gu-AGNCs 0 0.361 ± 0.002 0.363 ± 0.002 0.361 ± 0.004 0.360 ± 0.002 0.361 ± 0.003 0.357 ± 0.002 0.361 ± 0.002 1 0.361 ± 0.001 0.374 ± 0.001 a 0.373 ± 0.001 0.374 ± 0.002 0.371 ± 0.003 0.372 ± 0.003 0.375 ± 0.002 2 0.365 ± 0.002 0.391 ± 0.004 aaa 0.393 ± 0.003 0.392 ± 0.006 0.393 ± 0.0008 0.393 ± 0.004 0.389 ± 0.002 3 0.371 ± 0.001 0.416 ± 0.003 aaa 0.412 ± 0.004 0.411 ± 0.002 0.410 ± 0.003 0.411 ± 0.002 0.413 ± 0.003 4 0.372 ± 0.003 0.433 ± 0.005 aaa 0.435 ± 0.003 0.433 ± 0.005 0.437 ± 0.003 0.439 ± 0.002 0.439 ± 0.002 5 0.373 ± 0.003 0.458 ± 0.003 aaa 0.460 ± 0.003 0.459 ± 0.004 0.459 ± 0.005 0.463 ± 0.001 0.458 ± 0.002 6 0.375 ± 0.003 0.475 ± 0.003 aaa 0.482 ± 0.001 0.478 ± 0.002 0.476 ± 0.001 0.478 ± 0.004 0.476 ± 0.006 7 0.387 ± 0.002 0.503 ± 0.0008 aaa 0.488 ± 0.002 bbb 0.495 ± 0.0004 b 0.487 ± 0.0006 bbb***# 0.489 ± 0.001 bbb*** 0.500 ± 0.002 ns 8 0.393 ± 0.001 0.516 ± 0.002 aaa 0.493 ± 0.002 bbb 0.503 ± 0.0008 bbb 0.494 ± 0.0004 bbb***# 0.493 ± 0.001 bbb*** 0.510 ± 0.002 ns 9 0.394 ± 0.003 0.532 ± 0.001 aaa 0.499 ± 0.004 bbb 0.517 ± 0.0009 b 0.506 ± 0.0004 bbb**ns 0.504 ± 0.004 bbb** 0.522 ± 0.003 bbb 10 0.401 ± 0.001 0.552 ± 0.009 aaa 0.501 ± 0.002 bbb 0.526 ± 0.002 bbb 0.513 ± 0.002 bbb***# 0.511 ± 0.003 bbb*** 0.533 ± 0.002 bbb 11 0.406 ± 0.002 0.566 ± 0.004 aaa 0.502 ± 0.002 bbb 0.537 ± 0.002 bbb 0.524 ± 0.001 bbb***# 0.513 ± 0.002 bbb*** 0.549 ± 0.002 bb 12 0.407 ± 0.004 0.573 ± 0.002 aaa 0.503 ± 0.006 bbb 0.538 ± 0.001 bbb 0.531 ± 0.0005 bbb***# 0.516 ± 0.002 bbb*** 0.550 ± 0.003 bbb Values are represented as mean ± SEM. Data were analyzed by one-way ANOVA followed by Tukey’s multiple comparison test (n = 6 each group). a p < 0.05, aaa p < 0.001 vs. NC group; p < 0.05, bb p < 0.001, bbb p < 0.001 vs. HFD group. **p < 0.01, ***p < 0.001 vs. HFD + Gu-AGNCs; # p < 0.01 vs. HFD + berberine NC: Normal control, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes, HFD: High fat diet, ns: non significant Insert Table 1 , 2 , 3 here Effect of Ber/Gu-AGNCs on food intake No significant difference was observed in daily intake of food by rats of all the groups (Data not shown). Effect of Ber/Gu-AGNCs on liver weight, adipose tissue weight, liver index and adiposity index Liver is a metabolizing organ that is liable to fat deposition and hence, excessive accumulation of fat resulted in significant increase in liver weight [ 44 ]. In our study, liver weight, liver index, adipose tissue weight and adiposity index were significantly higher in the HFD treated control rats. HFD treated rats showed significant increase in liver weight, liver index (%), adipose tissue weight and adiposity index (%) on 85th day in comparison to normal control group (p < 0.001). Oral treatment with orlistat (20 mg/kg), berberine (10 mg/kg), Ber/Gu-AGNCs (10 and 20 mg/kg) and Gu-AGNCs (blank) once daily for 6 consecutive weeks (from 7th week to 12th week) significantly reversed HFD-induced increase of liver weight (p < 0.001 for all the five treatments), liver index (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.05 respectively), adipose tissue weight (p < 0.001 for all the five treatments) and adiposity index (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.01 respectively). Furthermore, Ber/Gu-AGNCs (10 and 20 mg/kg) showed a significant reversal of these parameters in comparison to Gu-AGNCs. In addition, 10 mg/kg dose of Ber/Gu-AGNCs also showed significant reversal of liver weight (p < 0.001), liver index (p < 0.05), total adipose weight (p < 0.001) and adiposity index (p < 0.05) in comparison to free berberine (10 mg/kg), indicating better effect of Ber/Gu-AGNCs than free berberine (Table 4 ). The decrease in liver weight by berberine is consistent with a previous study [ 45 ]. The role of guar gum in lowering liver weight and adipose tissue weight has been described in a previous study [ 42 ]. Hence, Ber/Gu-AGNCs showed a better effect in lowering liver weight, adipose tissue weight, liver index and adiposity index than free berberine and Gu-AGNCs. Table 4 Effect of Ber/Gu-AGNCs on liver weight, liver index, adipose tissue weight and adiposity index in HFD-induced obese rats on 85th day Groups Liver weight (g) Liver index (%) Total adipose tissue weight (g) Adiposity index (%) NC 5.03 ± 0.08 2.92 ± 0.05 4.03 ± 0.09 2.34 ± 0.05 HFD 10.01 ± 0.04 aaa 3.94 ± 0.04 aaa 8.3 ± 0.11 aaa 3.26 ± 0.04 aaa HFD + orlistat 6.61 ± 0.07 bbb 3.05 ± 0.019 bbb 5.2 ± 0.09 bbb 2.39 ± 0.03 bbb HFD + Ber 8.48 ± 0.06 bbb 3.59 ± 0.02 bbb 6.48 ± 0.09 bbb 2.74 ± 0.04 bbb HFD + Ber/Gu-AGNCs (10 mg/kg) 7.8 ± 0.05 bbb***### 3.38 ± 0.02 bbb***# 5.93 ± 0.02 bbb***### 2.57 ± 0.007 bbb***# HFD + Ber/Gu-AGNCs (20 mg/kg) 7.23 ± 0.13 bbb*** 3.22 ± 0.05 bbb*** 5.71 ± 0.04 bbb*** 2.54 ± 0.0 bbb*** HFD + Gu-AGNCs 9.18 ± 0.10 bbb 3.77 ± 0.04 b 7.46 ± 0.02 bbb 3.07 ± 0.008 bb Values are represented as mean ± SEM. Data were analyzed by one-way ANOVA followed by Tukey’s multiple comparison test (n = 6 each group). aaa p < 0.001 vs. NC group; b p < 0.05, bb p < 0.05, bbb p < 0.001 vs. HFD group; ***p < 0.001 vs. HFD + Gu-AGNCs; # p < 0.05, ### p < 0.001 vs. HFD + berberine NC: Normal control, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes, HFD: High fat diet Insert Table 4 here Effect of Ber/Gu-AGNCs on Serum lipid profile and atherogenic index (AI) Serum levels of TC, TG, LDL-c, VLDL-c; and atherogenic index increased significantly (p < 0.001), but HDL-c levels decreased significantly (p < 0.001) in HFD treated rats in comparison to normal control rats. Oral treatment with orlistat (20 mg/kg), berberine (10 mg/kg), Ber/Gu-AGNCs (10 and 20 mg/kg) and Gu-AGNCs significantly (p < 0.001) reversed HFD-induced increase of TC, TG, LDL-c, VLDL-c levels, and atherogenic index; and also significantly (p < 0.001) reversed HFD-induced decrease of HDL-c. Ber/Gu-AGNCs (10 and 20 mg/kg) significantly decreased TC (p < 0.001), TG (p < 0.001), LDL-c (p < 0.001), VLDL-c (p < 0.001) levels; and atherogenic index (p < 0.001) when compared to Gu-AGNCs. Moreover, Ber/Gu-AGNCs (10 mg/kg) significantly decreased TC (p < 0.001), TG (p < 0.001), LDL-c (p < 0.001), VLDL-c (p < 0.001) levels; and atherogenic index (p < 0.001) when compared to free berberine (10 mg/kg) [Table 5 ]. The lipid lowering effect of free berberine is also substantiated with an earlier study [ 46 ]. The lipid lowering effect of guar gum and gum acacia has also been described in a previous study [ 47 , 48 ]. Hence, Ber/Gu-AGNCs showed a better anti-hyperlipidemic effect than free berberine and Gu-AGNCs. Table 5 Effect of Ber/Gu-AGNCs on serum TC, TG, HDL-c, LDL-c, VLDL-c levels and atherogenic index in HFD-induced obese rats on 85th day Lipid levels (mg/dl) Groups TC TG HDL-c LDL-c VLDL-c AI (TG/HDL) NC 74.55 ± 0.95 60.35 ± 0.52 44.70 ± 0.90 17.77 ± 0.78 12.07 ± 0.10 1.35 ± 0.03 HFD 136.13 ± 0.81 aaa 120.74 ± 0.52 aaa 20.78 ± 0.52 aaa 91.20 ± 1.0 aaa 24.14 ± 0.10 aaa 5.82 ± 0.14 aaa HFD + Orlistat (20 mg/kg) 85.3 ± 0.45 bbb 62.8 ± 1.02 bbb 42.2 ± 0.23 bbb 30.54 ± 0.64 bbb 12.56 ± 0.20 bbb 1.48 ± 0.02 bbb HFD + Ber (10 mg/kg) 107.23 ± 0.44 bbb 93.96 ± 0.54 bbb 29.36 ± 0.17 bbb 59.07 ± 0.55 bbb 18.79 ± 0.10 bbb 3.20 ± 0.02 bbb HFD + Ber/Gu-AGNCs (10 mg/kg) 99.95 ± 0.54 bbb***### 84.18 ± 0.98 bbb***### 33.13 ± 0.13 bbb***### 49.98 ± 0.72 bbb***### 16.83 ± 0.19 bbb***### 2.54 ± 0.02 bbb***### HFD + Ber/Gu-AGNCs (20 mg/kg) 91.86 ± 0.51 bbb*** 72.16 ± 0.65 bbb*** 37.11 ± 0.17 bbb*** 40.31 ± 0.49 bbb*** 14.43 ± 0.13 bbb*** 1.94 ± 0.01 bbb*** HFD + Gu-AGNCs 122.53 ± 0.62 bbb 109.54 ± 0.76 bbb 24.21 ± 0.45 bbb 76.41 ± 0.50 bbb 21.90 ± 0.15 bbb 4.53 ± 0.10 bbb Values are represented as mean ± SEM. Data were analyzed by one-way ANOVA followed by Tukey’s multiple comparison test (n = 6 each group). aaa p < 0.001 vs. NC group. bbb p < 0.001 vs. HFD group; ***p < 0.001 vs. Gu-AGNCs; ### p < 0.001 vs. berberine. TC- total cholesterol, TG - total triglycerides, HDL-c – high-density lipoprotein-cholesterol, LDL-c - low-density lipoprotein-cholesterol, VLDL-c – very-low density lipoprotein-cholesterol NC: Normal control, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes, HFD: High fat diet Insert Table 5 here Effect of Ber/Gu-AGNCs on liver enzymes (SGOT and SGPT) SGOT and SGPT are the most important liver biomarkers enzymes and their elevated level in serum indicates hepatocyte damage [ 49 ]. The levels of these enzymes were significantly higher in HFD treated rats than in normal control rats. These results are in agreement with earlier studies [ 50 , 51 ]. SGOT and SGPT were significantly (p < 0.001) elevated in HFD treated rats in comparison to normal control rats. Oral treatment with orlistat (20 mg/kg), berberine (10 mg/kg), Ber/Gu-AGNCs (10 mg/kg and 20 mg/kg) and Gu-AGNCs (blank) significantly (p < 0.001) reversed HFD-induced increase of SGOT and SGPT levels. Moreover, Ber/Gu-AGNCs (10 and 20 mg/kg) also showed significant decrease of SGOT (p < 0.001) and SGPT (p < 0.001) levels as compared to Gu-AGNCs, indicating potentiation of hepatoprotective effect of Gu-AGNCs. Also, Ber/Gu-AGNCs (10 mg/kg) showed significant decrease of SGOT (p < 0.001) and SGPT (p < 0.001) as compared to free berberine (10 mg/kg) [Table 6 ]. The effect of berberine in decreasing SGOT and SGPT levels is reported by an earlier study [ 45 ]. The hepatoprotective effect of gum acacia against CCl 4 -induced hepatotoxicity has been described in an earlier study [ 52 ]. Hence, Ber/Gu-AGNCs displayed a better hepatoprotective effect than free berberine and Gu-AGNCs. Table 6 Effect of Ber/Gu-AGNCs on SGOT and SGPT levels in HFD-induced obese rats on 85th day Groups SGOT (U/L) SGPT (U/L) NC 58.70 ± 0.35 41.45 ± 0.30 HFD 125.56 ± 1.17 aaa 82.28 ± 0.58 aaa HFD + Orlistat (20 mg/kg) 63.80 ± 0.48 bbb 51.28 ± 0.34 bbb HFD + Ber (10 mg/kg) 80.33 ± 0.36 bbb 70.01 ± 0.25 bbb HFD + Ber/Gu-AGNCs (10 mg/kg) 75.78 ± 0.79 bbb***### 66.39 ± 0.51 bbb***### HFD + Ber/Gu-AGNCs (20mg/kg) 69.80 ± 0.62 bbb*** 59.45 ± 0.47 bbb*** HFD + Gu-AGNCs 99.46 ± 0.69 bbb 77.48 ± 049 bbb Values are represented as mean ± SEM. Data were analyzed by one-way ANOVA followed by Tukey’s multiple comparison test (n = 6 each group). aaa p < 0.001 vs NC; bbb p < 0.001 vs. HFD group;***p < 0.001 vs. HFD + Gu-AGNCs; ### p < 0.001 v s. HFD + berberine NC: Normal control, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes, HFD: High fat diet Insert Table 6 here Effect of Ber/Gu-AGNCs on liver catalase, reduced glutathione (GSH) and malondialdehyde (MDA) levels High fat diet treated rats showed significant increase of MDA levels, and decrease in catalase activity and GSH levels in contrast to normal control rats, indicating induction of oxidative stress. These findings are also supported by an earlier study [ 53 ]. MDA is a product of lipid peroxidation, which is a marker for oxidative stress. In liver tissues, increased accumulation of fat leads to the production of large free radicals which in turns leads to lipid peroxidation and oxidative stress [ 54 ]. Catalase and GSH play an important roles in antioxidant defense processes [ 55 ]. The hepatic activities of catalase and reduced glutathione were significantly (p < 0.001) decreased while the level of MDA was significantly (p < 0.001) increased in HFD treated rats in comparison to normal control rats. Oral treatment with orlistat (20 mg/kg), berberine (10 mg/kg), Ber/Gu-AGNCs (10 and 20 mg/kg) and Gu-AGNCs (blank) significantly reversed HFD-induced decrease of catalase (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.05 respectively) and GSH activities (p < 0.001 for all the five treatments), and also significantly (p < 0.001 for all the five treatments) reversed HFD-induced increase of MDA level. Ber/Gu-AGNCs (10 and 20 mg/kg) also significantly increased catalase (p < 0.001) and GSH (p < 0.001) activities; and decreased MDA levels (p < 0.001) in comparison to Gu-AGNCs. Moreover, Ber/Gu-AGNCs (10 mg/kg) exhibited a significant increase of catalase (p < 0.01) and GSH (p < 0.001) activities; and decrease of MDA level (p < 0.001) as compared to free berberine (10 mg/kg) (Fig. 1 a, b and c). Berberine has been reported to attenuate oxidative stress in rats with non-alcoholic fatty liver disease [ 56 ]. The role of gum acacia and guar gum in decreasing markers of oxidative stress in the liver of high fat diet-induced obese mice and high fat diet-fed hamsters respectively has been described in an earlier study [ 57 , 58 ]. Hence, Ber/Gu-AGNCs showed better oxidative stress ameliorating effect than free berberine and Gu-AGNCs. Insert Fig. 1 a,b, c here Effects of Ber/Gu-AGNCs on blood glucose level on 85th day HFD treated rats showed significant (p < 0.001) increase in blood glucose level on 85th day in comparison to normal control group. Oral treatment with orlistat (20 mg/kg), berberine (10 mg/kg), Ber/Gu-AGNCs (10 and 20 mg/kg) and Gu-AGNCs once daily for 6 consecutive weeks (from 7th week to 12th week) significantly decreased (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001) blood glucose level in comparison to HFD treated control group. Ber/Gu-AGNCs (10 and 20 mg/kg) also showed significant (p < 0.001) decrease in blood glucose level as compared to Gu-AGNCs (blank). In addition, 10 mg/kg dose of Ber/Gu-AGNCs also displayed significant (p < 0.001) decrease in blood glucose levels in comparison to free berberine (10 mg/kg) (Fig. 2 ). Berberine decreased blood glucose level in obese rats is also supported by an earlier study [ 59 ]. The effect of gum acacia and guar gum in decreasing blood glucose levels has been described in an earlier study [ 60 , 42 ]. Hence, Ber/Gu-AGNCs showed better glucose lowering effect than free berberine and Gu-AGNCs. Insert Fig. 2 here Histopathological studies Microscopic evaluation of liver of normal control rat (Fig. 3 a) revealed normal histological hepatic architecture arranged as cords of hepatocytes with central vein and portal triads without any pathological alterations. Micrograph of liver of rat fed with HFD showed hepatosteatosis characterized by fatty vacuolar degenerative changes in hepatic cells and formation of fatty cysts in hepatic parenchyma (Fig. 3b2), sinusoidal dilatation, congestion of central veins and focal area of hepatic necrosis characterized by inflammatory cell infiltration (Fig. 3b1). These results are substantiated by an earlier study [ 61 ]. HFD + Gu-AGNCs treated rat also showed congestion of central veins and sinusoidal dilatation but focal area of hepatic necrosis was not observed, indicating some amount of hepatoprotective effect (Fig. 3 g). The decrease in hepatocyte degeneration by gum acacia in the histological analysis of liver tissue has been described in an earlier study [ 57 ]. Rat treated with HFD along with orlistat showed almost normal histological architecture as evident by less lipid droplets accumulation, no necrosis and inflammatory reaction (Fig. 3 c).The liver of berberine-treated rat showed improvement as revealed by less dilatation of sinusoids and decreased number of lipid droplets (Fig. 3 d). The observed results with berberine were substantiated by an earlier reported study [ 62 ]. In contrast, rats treated with Ber/Gu-AGNCs showed better improvement as central vein appeared normal, no appearance of dilated sinusoids and very few lipid droplets in lower dose group (10 mg/kg) and almost absence of lipid droplets in high dose group (20 mg/kg) (Fig. 3 e and f). Insert Fig. 3 here (a-g) In histological micrograph of adipose tissue, there was hypertrophy (increased size) of retroperitoneal adipocytes in HFD treated rat (Fig. 4 b) as compared to normal control rat (Fig. 4 a). These findings are agreeing with a previous study [ 63 ]. However, the rat treated with orlistat showed significant decrease in size of adipocytes (Fig. 4 c). Berberine + HFD treated rat (Fig. 4 d) revealed decrease in size of adipocytes as compared to HFD treated rat. These results are substantiated by an earlier study [ 64 ]. Ber/Gu-AGNCs (10 and 20 mg/kg) + HFD treated rat also showed marked decrease in size of adipocytes (Fig. 4 e and f). Gu-AGNCs (blank) + HFD treated rat (Fig. 4 g) showed only mild decrease in size of adipocytes in comparison to HFD treated rat. Hence, Ber/Gu-AGNCs showed better improvement in comparison to Gu-AGNCs and free berberine Insert Fig. 4 here (4a-g) The better anti-obesity activity of Ber/Gu-AGNCs in comparison to free berberine and Gu-AGNCs (blank) in the above studied parameters might be due to improvement in bioavailability, solubility and stability of berberine after encapsulation within polymeric nanoparticles. These results are substantiated by an earlier study where nanoencapsulation improved solubility and stability of trans -Resveratrol, and thereby their anti-obesity activity [ 65 ]. Similarly, Zhang et al (2013) reported enhanced anti-obesity activity of epigallocatechin gallate by nanoencapsulation [ 66 ]. In addition, guar gum and gum acacia possesses significant anti-obesity activity. So, the anti-obesity properties of gums may add a synergistic effect in berberine nanoformulation. Conclusion In the current work, berberine loaded guar-acacia gum nanocomplexes (Ber/Gu-AGNCs) were successfully prepared via ionic complexation method using guar gum and gum acacia as nanocarriers. The nanocomplexes exhibited a homogenous morphological structure, appropriate diameter, good zeta potential and excellent encapsulation efficiency. In vivo studies in high-fat diet induced obesity model in rats showed better anti-obesity effect of Ber/Gu-AGNCs (10 and 20 mg/kg) than free berberine and blank nanocomplexes. Further studies can be carried out to explore the other possible mechanisms for better anti-obesity effect of Ber/Gu-AGNCs. Moreover, the study can also be extended clinically for better management of obesity with Ber/Gu-AGNCs. Declarations D ata availability The data provided in this manuscript is new and has not published elsewhere. This data includes figures (images), and tables. The data generated during the current study are available from the corresponding author upon reasonable request. Acknowledgments The authors acknowledge Guru Jambheshwar University of Science & Technology, (Hisar), for the financial support in the form of University Research Fellowship (URF) (Endst.No.Sch & SC/ST/20/626-632); Sophisticated Analytical Instrumentation Facility (SAIF), AIIMS, New Delhi and Luvas (Hisar) for providing facilities for carrying out this research work. Funding This study was funded by Guru Jambheshwar University of Science & Technology, Hisar for the University Research Fellowship (URF) (Grant Agreement No. Endst.No.Sch & SC/ST/20/626-632). Author Information Authors and Affiliations Department of Bio & Nano Technology, Guru Jambheshwar University of Science & Technology, Hisar , 125001 , India Jyoti Bakshi, Assim Verma, Sapna Grewal & Santosh Kumari Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology, Hisar , 125001 , India Prity Lathar and Dinesh Dhingra Department of Veterinary Pathology, Lala Lajpat Rai University of Veterinary & Animal Sci ences, Hisar , 125001 , India Deepika Lather Author contribution s SK: conceptualization. SK and DD: methodology. JB: formal analysis and investigation. JB, DD and DL: writing original draft preparation. DD, SG, PL and AV: Funding acquisition. DD and PL: Resources. JB, SK and DD: supervision. All the authors have checked the manuscript and have agreed to the submission. Ethics declarations Competing Interests The authors declare no competing interests. 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Liang, J. Zhang, et al., Exp Ther Med (2019) https://doi.org/10.3892/etm.2019.7208 H.H. Musa, J.S. Fedail, A.A. Ahmed, T.H. Musa, A.Z. Sifaldin (2016) http://doi.org/10.1039/9781782623830-00256 D.C. Kuo, S.P. Hsu, C.T. Chien, J Biomed Sci (2009) https://doi.org/10.1186/1423-0127-16-15 R. Tiwari, P. Gupta, A.K. Verma, Int J Pharm Sci Drug Res (2021) https://doi.org/10.25004/IJPSDR.2021.130505 O.D. Nasir, J. Biol. Agric Healthcare. 4, 34 (2014) N.F. Hassan, G.M. Soliman, E.F. Okasha, A.M. Shalaby, J Microsc Ultrastruct (2018) https://doi.org/10.4103/jmau.jmau_5_18 Z. Zhang, Z. Li, X. Meng, S. Yao, L. Jin, J. Yang, et al., Sci Reports (2016) https://doi.org/10.1038/srep20848 R. Mopuri, M. Ganjayi, K.S. Banavathy, B.N. Parim, B. Meriga, BMC Complement Altern Med (2015) https://doi.org/10.1186/s12906-015-0598-3 K.H. Hwang, J.Y. Ahn, S. Kim, T.Y. Ha, J Food Sci Nutr (2009) http://doi.org/10.3746/jfn.2009.14.4.298 Y. Zu, H. Overby, G. Ren, Z. Fan, L. Zhao, S. Wang, Colloids Surf B Biointerfaces (2018) https://doi.org/10.1016/j.colsurfb.2017.12.044 J. Zhang, S. Nile, S. Wang, J Agric Food Chem (2013) https://doi.org/10.1021/jf4023004 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3928032","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":272656737,"identity":"2df9c250-612e-4f37-8b94-c382306132b4","order_by":0,"name":"Jyoti Bakshi","email":"","orcid":"","institution":"Guru Jambheshwar University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Jyoti","middleName":"","lastName":"Bakshi","suffix":""},{"id":272656738,"identity":"fc97c4bd-670a-424f-a1c4-15bd54f9222c","order_by":1,"name":"Prity Lathar","email":"","orcid":"","institution":"Guru Jambheshwar University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Prity","middleName":"","lastName":"Lathar","suffix":""},{"id":272656739,"identity":"dfbe0092-a93d-4932-9020-b51f5207fbf3","order_by":2,"name":"Assim Verma","email":"","orcid":"","institution":"Guru Jambheshwar University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Assim","middleName":"","lastName":"Verma","suffix":""},{"id":272656740,"identity":"3734951d-b77a-473e-97ae-93947882ca23","order_by":3,"name":"Deepika Lather","email":"","orcid":"","institution":"Lala Lajpat Rai University of Veterinary \u0026 Animal Sciences","correspondingAuthor":false,"prefix":"","firstName":"Deepika","middleName":"","lastName":"Lather","suffix":""},{"id":272656741,"identity":"1ba8c2b8-000b-4c8a-99af-6a1edfc85cc2","order_by":4,"name":"Sapna Grewal","email":"","orcid":"","institution":"Guru Jambheshwar University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Sapna","middleName":"","lastName":"Grewal","suffix":""},{"id":272656742,"identity":"950c72bd-8036-45cf-92e1-b90f9fd371ec","order_by":5,"name":"Dinesh Dhingra","email":"","orcid":"","institution":"Guru Jambheshwar University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Dinesh","middleName":"","lastName":"Dhingra","suffix":""},{"id":272656743,"identity":"322d7602-3824-46c1-b9e1-6a7ba24381e0","order_by":6,"name":"Santosh Kumari","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYBACCSBmZmA7wMAP4iUUkKJFsgGkxYAULQYHQFxitEi2nzH+XFB2x974/OrEDw8MGOT5xQ7g1yLNk2MmPePcs8RtN95ulgA6zHDm7AT8WuQYcsyYedsOJ5jdOLsBpCXB4DYhLfxvjD8Dtdgbzzi7+QdRWqQlcgykgVoYN/D3biPOFskZz8qkeYB+mXGDd5tFgoEEYb9InE/e/JkHGGL8/Wc33/xRYSPPL01AC5JmsEoJYpWDAP8BUlSPglEwCkbBSAIA9slElc+fAZoAAAAASUVORK5CYII=","orcid":"","institution":"Guru Jambheshwar University of Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"Santosh","middleName":"","lastName":"Kumari","suffix":""}],"badges":[],"createdAt":"2024-02-04 15:21:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3928032/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3928032/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51181256,"identity":"7b3ebf94-4f97-449b-9ed5-467c29ef6d24","added_by":"auto","created_at":"2024-02-15 14:54:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":325621,"visible":true,"origin":"","legend":"\u003cp\u003eEffect of Ber/Gu-AGNCs on (\u003cstrong\u003ea\u003c/strong\u003e) Catalase, (\u003cstrong\u003eb\u003c/strong\u003e) GSH and (\u003cstrong\u003ec\u003c/strong\u003e) MDA levels in liver tissue. Data were analyzed by one-way ANOVA followed by Tukey’s multiple comparison test (n = 6 each group). \u003csup\u003eaaa\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs. \u003c/em\u003enormal control (NC) group. \u003csup\u003eb\u003c/sup\u003ep \u0026lt; 0.05, \u003csup\u003ebbb\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs.\u003c/em\u003e HFD group.***p \u0026lt; 0.001 \u003cem\u003evs.\u003c/em\u003e HFD + Gu-AGNCs; \u003csup\u003e##\u003c/sup\u003ep \u0026lt; 0.01, \u003csup\u003e###\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs.\u003c/em\u003e HFD + berberine (10 mg/kg)\u003c/p\u003e\n\u003cp\u003eNC: Normal control, HFD: High fat diet, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs, ns = non-significant\u003c/p\u003e","description":"","filename":"F1.png","url":"https://assets-eu.researchsquare.com/files/rs-3928032/v1/e6988cc52ea37b6e063d40b9.png"},{"id":51181255,"identity":"2fb8487d-ac71-4fdb-a358-88931cdf8ae6","added_by":"auto","created_at":"2024-02-15 14:54:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":497548,"visible":true,"origin":"","legend":"\u003cp\u003eEffect of Ber/Gu-AGNCs on blood glucose level. Values are represented as mean ± SEM. Data were analyzed by one-way ANOVA followed by Tukey’s multiple comparison test (n = 6 each group). \u003csup\u003eaaa\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs\u003c/em\u003e. NC group; \u003csup\u003ebbb\u003c/sup\u003ep \u0026lt; 0.001\u003cem\u003evs\u003c/em\u003e. HFD group; ***p \u0026lt; 0.001 \u003cem\u003evs. \u003c/em\u003eHFD + Gu-AGNCs; \u003csup\u003e###\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs. \u003c/em\u003eHFD + berberine\u003c/p\u003e\n\u003cp\u003eNC: Normal control group, HFD: High fat diet, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes\u003c/p\u003e","description":"","filename":"F2.png","url":"https://assets-eu.researchsquare.com/files/rs-3928032/v1/9b5ac9e725d90dffaed80adb.png"},{"id":51181258,"identity":"b5ecd80d-0821-46e0-be38-e1a783682a1a","added_by":"auto","created_at":"2024-02-15 14:54:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":6393182,"visible":true,"origin":"","legend":"\u003cp\u003eHistology of liver of rats; (\u003cstrong\u003ea\u003c/strong\u003e) Normal control rat showing normal hepatic architecture (red arrow); (\u003cstrong\u003eb1\u003c/strong\u003e) HFD treated rat showing congestion in central vein (yellow arrow), dilatation of sinusoids (dark blue arrow), foci of inflammatory cells infiltration (black arrow), (\u003cstrong\u003eb2\u003c/strong\u003e) fatty cysts (orange arrow), (\u003cstrong\u003ec\u003c/strong\u003e) orlistat + HFD treated rat showing no necrosis and inflammatory reaction (\u003cstrong\u003ed\u003c/strong\u003e) berberine + HFD treated rat showing dilatation of sinusoids (dark blue arrow) and presence of lipid droplets (blue arrow) (\u003cstrong\u003ee\u003c/strong\u003e) Ber/Gu-AGNCs (10 mg/kg) + HFD treated rat showing no dilatation of sinusoids and less number of lipid droplets (blue arrow) (\u003cstrong\u003ef\u003c/strong\u003e) Ber/Gu-AGNCs (20 mg/kg) + HFD treated rat showing very few lipid droplets (blue arrow) and (\u003cstrong\u003eg\u003c/strong\u003e) Gu-AGNCs + HFD treated rat showing congestion of central vein (yellow arrow) and dilatation of sinusoids (dark blue arrow)\u003c/p\u003e\n\u003cp\u003eNC: Normal control group, HFD: High fat diet, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes\u003c/p\u003e","description":"","filename":"F3.png","url":"https://assets-eu.researchsquare.com/files/rs-3928032/v1/0d3f688df50bec23de705327.png"},{"id":51181257,"identity":"05f54219-2f82-43e6-a54a-c5184c9e8bcb","added_by":"auto","created_at":"2024-02-15 14:54:07","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":4185814,"visible":true,"origin":"","legend":"\u003cp\u003eHistology of adipose tissue of rats; (\u003cstrong\u003ea\u003c/strong\u003e) Normal control rat (\u003cstrong\u003eb\u003c/strong\u003e) HFD treated rat (\u003cstrong\u003ec\u003c/strong\u003e) orlistat + HFD treated rat (\u003cstrong\u003ed\u003c/strong\u003e) berberine + HFD treated rat (\u003cstrong\u003ee\u003c/strong\u003e) Ber/Gu-AGNCs (10 mg/kg) + HFD treated rat (\u003cstrong\u003ef\u003c/strong\u003e) Ber/Gu-AGNCs (20 mg/kg) + HFD treated rat (\u003cstrong\u003eg\u003c/strong\u003e) Gu-AGNCs + HFD treated rat\u003c/p\u003e\n\u003cp\u003eNC: Normal control group, HFD: High fat diet, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes\u003c/p\u003e","description":"","filename":"F4.png","url":"https://assets-eu.researchsquare.com/files/rs-3928032/v1/602796bbcf706527c1a0e1d1.png"},{"id":59475156,"identity":"4f1b9720-70ca-494a-b1cb-89f77f7fbe8b","added_by":"auto","created_at":"2024-07-02 08:40:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":13161119,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3928032/v1/a2f8aea9-22f0-460b-bfe3-72e850fc7cb0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Potentiation of anti-obesity activity of berberine through its encapsulation in guar-acacia gum nanocomplexes in Wistar albino rats","fulltext":[{"header":"Introduction","content":"\u003cp\u003eObesity is a common health disorder described by a severe buildup of high proportion of body fat in adipose tissues and hence resulted in an increase in body weight [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The changing life style, lack of exercise, high calorie food, genetic background, etc are some of the factors that causes imbalance between the intake and expenditure of energy, thereby leading to the development of obesity [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The prevalence of obesity has increased globally over the past decades cutting across age groups, ethnicity and sex; and turned to be the major contributor for the development of various diseases such as type 2 diabetes, cardiovascular disorders, hypertension and certain cancers [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Although few FDA approved synthetic drugs like orlistat and sibutramine show remarkable effect in the management of obesity, but these are not preferred for long term usage due to their side effects such as headache, constipation, weight rebound on discontinuation, etc [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Therefore, there is an ever-pressing need for developing safer and effective anti-obesity medicines from natural sources.\u003c/p\u003e \u003cp\u003eBerberine is a natural plant alkaloid, derived from many plants like \u003cem\u003eBerberis aristata\u003c/em\u003e, \u003cem\u003eCoptis chinensis\u003c/em\u003e, \u003cem\u003eHydrastis canadensis\u003c/em\u003e, etc [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Berberine showed protective effect against type- 2 diabetes and hyperlipidemia in patients [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Berberine has various pharmacological properties in laboratory animals such as anti-inflammatory [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], antioxidant [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], anti-obesity[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], etc. However, despite its promising multi-spectrum pharmacological activities, berberine has been reported for its low bioavailability after oral administration due to its poor solubility and gastrointestinal absorption. To overcome these limitations, encapsulating drugs in a suitable nanocarrier can be considered. Some pre-clinical studies have suggested the improved therapeutic potential of berberine \u003cem\u003evia\u003c/em\u003e polymeric nanoencapsulation [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The cationic nature of berberine displays a favorable possibility of its interaction with many polymeric carriers. Various polymers have been used for the development of berberine-containing nanoparticles including chitosan [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], chitosan-alginate [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], fucose-chitosan/heparin [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], and polycaprolactone [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], etc. \u003cem\u003eIn vivo\u003c/em\u003e studies showed improved bioavailability of berberine when loaded in chitosan-coated alginate/gelatin microspheres [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. But nowadays the use of natural gums as excipients has increased in the pharmaceutical industry due to their sustained drug releasing effect [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and enhancement of bioavailability of the bioactive compounds [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGuar gum is a non-ionic heteropolysaccharide, and obtained from the plant \u003cem\u003eCyamopsis tetragonoloba\u003c/em\u003e [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Guar gum possesses fascinating features desirable for drug delivery such as good stability [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and excellent drug retarding properties [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Besides these, there is protective role of guar gum in high fat diet-induced obesity in rats [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Another extensively used anionic heteropolysaccharide obtained from \u003cem\u003eAcacia senegal and Acacia seyal\u003c/em\u003e trees is gum acacia [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Owning to its outstanding safety profile, biocompatibility and biodegradability, gum acacia has achieved greater attention in the pharmaceutical industry [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Gum acacia has been reported to show protective effect against high fat diet-induced obesity in mice [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Additionally, gum acacia has been widely used for improving encapsulation efficiency [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] and bioavailability of the encapsulated drug [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn view of the above mentioned interesting properties of gum acacia and guar gum, this study was designed to evaluate potentiating effect of encapsulation of berberine in guar-acacia gum nanocarriers against HFD-induced obesity in rats. Till now, there are no reports in the literature on improved anti-obesity activity of berberine loaded guar-acacia gum nanocomplexes.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDrugs and Chemicals\u003c/h2\u003e \u003cp\u003eBerberine HCl was obtained from MP Biomedicals Pvt. Ltd. (Mumbai, India). Pure cholesterol, cholic acid, Tween 20, gum acacia powder, guar gum powder, glutaraldehyde, Ellman\u0026rsquo;s reagent (5,5\u0026rsquo;-dithiobis-(2-nitrobenzoic acid), EDTA, potassium chloride, mannitol and sodium lauryl sulfate were supplied by Hi-Media Lab. Pvt. Ltd. (Mumbai, India). Orlistat, n-butanol, acetic acid, trichloroacetic acid, thiobarbituric acid, pyridine and hydrogen peroxide were brought from Sigma-Aldrich, St. Louis (USA). Sodium dihydrogen phosphate (NaH\u003csub\u003e2\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e) and di-sodium hydrogen phosphate (Na\u003csub\u003e2\u003c/sub\u003eHPO\u003csub\u003e4\u003c/sub\u003e) were obtained from SISCO Research Laboratories Pvt. Ltd. (Mumbai, India). Total protein, Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, Serum glutamic pyruvic transaminase (SGPT) and SGOT (serum glutamic oxaloacetic transaminase) were determined using kits (Erba, Transasia Bio-Medicals Ltd. Solan, India). Lard was purchased from slaughter house.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eExperimental Animals\u003c/h2\u003e \u003cp\u003eWistar albino female rats (body weight 130\u0026ndash;140 g; 4\u0026ndash;6 months old) were procured from Experimental Animal Facility, Guru Jambheshwar University of Science and Technology, Hisar (Haryana, India). The number of animals use in this research study and experimental protocol were approved by Institutional Animal Ethics Committee (IAEC) in its meeting held on 10th Feb., 2022 [IAEC minutes letter No. IAEC/2022/10\u0026ndash;18, dated 22-2-2022]. All the animals were housed in polypropylene cages (43 \u0026times; 27 \u0026times; 15 cm) and were maintained under standard laboratory conditions i.e., 12-h light/12-h dark cycle, temperature 24\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u0026deg;C for at least 5 days before the start of experiments. Food and water were given \u003cem\u003ead libitum\u003c/em\u003e to the animals.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePreparation and characterization of Ber/Gu-AGNCs\u003c/h2\u003e \u003cp\u003eBer/Gu-AGNCs were synthesized \u003cem\u003evia\u003c/em\u003e the ionic complexation method using guar gum and gum acacia as polymers and Tween 20 as surfactant; and characterized by dynamic light scattering, FTIR and TEM. The details were given in our previous study [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Similarly, blank (Gu-AGNCs) was prepared consisting of guar gum and gum acacia but without berberine.\u003c/p\u003e \u003cp\u003e \u003cb\u003eEvaluation of\u003c/b\u003e \u003cb\u003ein vivo\u003c/b\u003e \u003cb\u003eAnti-obesity activity of Ber/Gu-AGNCs\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eHigh fat diet-induced obesity\u003c/h2\u003e \u003cp\u003eExperimental obesity was induced in rats by feeding high fat diet (HFD) for a period of twelve weeks consisting of normal feed containing lard (10% w/w), pure cholesterol (2% w/w) and cholic acid (0.25% w/w) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Diet was freshly prepared each day. Orlistat was dissolved in 1% v/v dimethyl sulfoxide in distilled water. Berberine was suspended in phosphate buffer (pH 7.4, 0.02 M) just before administration to the animals. The volume of oral administration of drug solution/vehicle was 1 ml /100 g body weight.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eExperimental protocol\u003c/h2\u003e \u003cp\u003eA total of 42 rats were used in the present study. Animals were categorized into following groups (n\u0026thinsp;=\u0026thinsp;6 rats each):\u003c/p\u003e \u003cp\u003eGroup I (Normal control): Rats were fed with normal diet for twelve weeks.\u003c/p\u003e \u003cp\u003eGroup II (HFD control): Rats were maintained on HFD for twelve weeks to induce obesity.\u003c/p\u003e \u003cp\u003eGroup III (Orlistat, 20 mg/kg, p.o.): Rats were maintained on HFD for 6 successive weeks. From the end of sixth weeks to the end of twelve weeks, orlistat was given orally 1 h before feeding the animals with HFD.\u003c/p\u003e \u003cp\u003eGroup IV (Berberine, 10 mg/kg, p.o.): Rats were maintained on HFD for 6 successive weeks. From the end of sixth weeks to the end of twelve weeks, berberine was given orally 1 h before feeding the animals with HFD.\u003c/p\u003e \u003cp\u003eGroups V and VI (Ber/Gu-AGNCs, 10 and 20 mg/kg respectively, p.o.): Rats were maintained on HFD for 6 successive weeks. From the end of sixth weeks to the end of 12 weeks, Ber/Gu-AGNCs were given orally 1 h before feeding the animals with HFD.\u003c/p\u003e \u003cp\u003eGroup VII (Gu-AGNCs, p.o.) - Rats were administered HFD for 6 successive weeks. From the end of sixth weeks to the end of 12 weeks, Gu-AGNCs were given orally 1 h before feeding the animals with HFD.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003eCollection of blood samples; and Isolation of liver and adipose tissue\u003c/h2\u003e \u003cp\u003eAt the end of 12 weeks, all the animals were sacrificed under anesthesia with chloroform and carbon dioxide. Blood samples (1 to 1.5 ml) were collected by carotid artery bleeding into sterilized centrifuge tubes. A small amount of blood was used for glucose estimation. The remaining blood was left for coagulation for 30 min and serum was collected by centrifugation at 3000 rpm at 4\u0026deg;C for 10 min using a refrigerated centrifuge (C-24Plus, RemiElektrotechnik Ltd., Maharashtra). The serum was stored at \u0026minus;\u0026thinsp;20\u0026deg; C for 1\u0026ndash;2 days and then used for biochemical estimations. Liver and adipose tissues (retroperitoneal and mesenteric) were removed from all the rats, then washed in cold physiological saline and weighed. The tissue samples were stored at \u0026minus;\u0026thinsp;20\u0026deg; C for 1\u0026ndash;2 days. Oxidative stress parameters were measured in liver homogenate of five rats of each group. Histopathological studies on liver and adipose tissue (retroperitoneal of one rat from each group) were carried out.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eMeasurement of body mass index (BMI), waist circumference (WC), liver index and adiposity index\u003c/h2\u003e \u003cp\u003eThe body weights of animals of all the groups were measured once in a week. Length of each rat was measured from its nose to anus. Waist circumference was measured on the largest zone of rat abdomen. Liver and adipose tissues (retroperitoneal and mesenteric) of rats were dissected out, rinsed with ice-cold phosphate-buffered saline (PBS, pH 7.4), and then weighed. BMI [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], adiposity index and liver index [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] were calculated according to the following formulae:\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003eBMI =\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\frac{\\text{Body weight (g)}}{{\\text{length}}^{\\text{2}}\\text{ (}{\\text{cm}}^{\\text{2}}\\text{)}}\\)\u003c/span\u003e\u003c/span\u003e\u003c/h2\u003e \u003cp\u003eAdiposity index (%)=\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\frac{\\text{ Retroperitoneal, mesenteric fat}}{\\text{body weight}}\\times 100\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003cp\u003eLiver index (%) =\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\frac{\\text{liver weight}}{\\text{body weight}}\\times 100\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eEstimation of blood glucose levels\u003c/h2\u003e \u003cp\u003eBlood glucose level was estimated using glucometer (BG-03 Model, Dr. Morepen Laboratories Ltd., Himachal Pradesh, India).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eBiochemical estimation in serum\u003c/h2\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003ch2\u003eEstimation of lipid profile and liver enzymes\u003c/h2\u003e \u003cp\u003eThe changes in lipid parameters like total cholesterol, triglycerides (TG), high density lipoprotein, SGOT and SGPT in serum samples were measured using biochemical kits as per the manufacturer\u0026rsquo;s instructions.\u003c/p\u003e \u003cp\u003eVery low-density lipoprotein (VLDL) and low-density lipoprotein cholesterol (LDL) were measured indirectly according to the Friedewald formula [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]:\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eVLDL\u0026thinsp;=\u0026thinsp;TG/5\u003c/h2\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003eLDL\u0026thinsp;=\u0026thinsp;TC- (HDL\u0026thinsp;+\u0026thinsp;VLDL)\u003c/h2\u003e \u003cp\u003eThe atherogenic index was calculated using the following formula [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]:\u003c/p\u003e \u003cp\u003eAtherogenic index (AI)\u0026thinsp;=\u0026thinsp;TC/HD\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eBiochemical estimations in liver homogenate\u003c/h2\u003e \u003cdiv id=\"Sec17\" class=\"Section3\"\u003e \u003ch2\u003eProtein content\u003c/h2\u003e \u003cp\u003eTotal protein content in tissue homogenate was estimated using commercial kit with bovine serum albumin as standard.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eEstimation of Reduced glutathione (GSH) levels\u003c/h2\u003e \u003cp\u003eThe levels of reduced glutathione in tissue homogenate were measured according to the procedure described in the previous study [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Briefly, 200 mg of liver tissue was homogenized in 8.0 ml of EDTA (0.02 M) in a homogenizer. To 5.0 ml of prepared homogenates, around 4 ml of distilled water and 1 ml of 50% trichloroacetic acid was added. The mixture was centrifuged at 3000 rpm for 15 min and supernatant was separated. To the obtained supernatant (approx. 2 ml), 4.0 ml of Tris buffer (0.4 M pH 8.9), and 0.1 ml of Ellman\u0026rsquo;s reagent (5, 5\u0026rsquo;-dithiobis-(2-nitrobenzoic acid) was added. The samples were mixed gently and absorbance was measured at 412 nm against reagent blank (without homogenate) using UV-Vis spectrophotometer (Genetix Biotech Asia Pvt. Ltd., New Delhi). Results were measured using the molar extinction coefficient of chromophore (1.34 \u0026times; 10\u003csup\u003e4\u003c/sup\u003e M\u003csup\u003e-1\u003c/sup\u003e cm\u003csup\u003e-1\u003c/sup\u003e) and expressed as nmol of GSH per mg of protein.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eEstimation of Catalase\u003c/h2\u003e \u003cp\u003eCatalase activity was measured according to the procedure as described earlier [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. 5% liver homogenate was prepared in ice-cold 50 mM phosphate buffer (pH 7.0) using a homogenizer. The homogenates were centrifuged at 10,000 rpm for 20 min at 4\u0026deg;C. About 50 \u0026micro;l of supernatant was added to a solution containing 2 ml of phosphate buffer (pH 7.0) and 1 ml of 30 mM hydrogen peroxide. Catalase activity was measured spectrophotometrically at 240 nm and expressed as nmole of H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eutilized/minute/mg of protein.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eEstimation of Malondialdehyde level (MDA)\u003c/h2\u003e \u003cp\u003eMalondialdehyde level was measured according the procedure as reported by Ohkawa et al [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Liver tissue (100 mg) was homogenized in 9.0 ml of 1.15% KCl by using a homogenizer. 0.2 ml of liver homogenate was added to reaction mixture consisted of 0.2 ml of 8.1% sodium lauryl sulphate, 1.5 ml of 20% acetic acid (pH 3.5) and 1.8 ml of 0.8% w/v aqueous solution of thiobarbituric acid. The total volume was made to 4 ml with distilled water and mixture was heated at 95\u0026deg; C for 60 min using a water bath. After cooling, 5 ml mixture of n-butanol and pyridine (15:1 v/v) and 1 ml of distilled water were added. The mixture was centrifuged at 4000 rpm for 10 min and upper organic layer was separated out. The absorbance of the upper layer was measured at 532 nm using UV-Vis spectrophotometer against a reagent blank. MDA concentration was calculated using extinction coefficient 1.56 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e M\u003csup\u003e-1\u003c/sup\u003e cm\u003csup\u003e-1\u003c/sup\u003e and expressed as nmol/mg of protein.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eHistopathological analysis\u003c/h2\u003e \u003cp\u003eThe histological features of adipose tissue and liver tissue from one rat of each experimental group were studied. Adipose and liver tissues were collected, washed in phosphate buffer and fixed in 10% v/v phosphate buffered formalin for 48 h. Formalin-fixed tissues were processed using different grades of ethanol (70%, 80%, 90% and 100%) and xylene followed by embedding in paraffin wax. Further sections of paraffin blocks of 4\u0026ndash;5 \u0026micro;m thicknesses were cut using rotary microtome (HistoCoreMulticut Semi-Automated rotary Microtome, Leica Biosystems, Mumbai, India) which were then stained with hematoxylin and eosin dyes [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. The stained tissues slides were examined at 200x magnification and pictured using a microscope (Olympus, CX41, Tokyo, Japan) to study histopathological alterations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe data were represented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard error of mean (SEM). The results were statistically analyzed by one-way ANOVA succeeded by Tukey multiple comparison test using GraphPad Prism v 5.01 software. Data having p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered to be statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results and Discussion","content":"\u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eSynthesis and characterization of Ber/Gu-AGNCs\u003c/h2\u003e \u003cp\u003eThe suspension of Ber/Gu-AGNCs was yellowish in color and odorless. The optimal calculated parameters were found to be a concentration of guar gum \u0026minus;\u0026thinsp;0.191 (% w/v), gum acacia \u0026minus;\u0026thinsp;0.271 (% w/v) and Tween 20\u0026ndash;2.66% as discussed in our previous study [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The particle size, PDI, zeta potential and entrapment efficiency of the optimized batch of Ber/Gu-AGNCs were found to be 290.2 nm, 0.230, \u0026minus;\u0026thinsp;26.8 mV and 96.5%, respectively.\u003c/p\u003e \u003cp\u003eA detailed explanation of the FTIR spectroscopy of Ber/Gu-AGNCs is given in our previous study. The data confirmed the successful encapsulation of berberine into the gum nanocomplexes without any unfavorable interaction between polymer and drug. TEM and SEM results showed spherical shaped nanocomplexes with size in the range of 100\u0026ndash;250 nm.\u003c/p\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003eIn vitro drug release of Ber/Gu-AGNCs\u003c/h2\u003e \u003cp\u003e \u003cem\u003eIn vitro\u003c/em\u003e drug release study showed that Ber/Gu-AGNCs have a sustained release behavior with 77.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7% of release in 48 h in contrast to their free forms.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section3\"\u003e \u003ch2\u003eEffect of Ber/Gu-AGNCs on High Fat Diet-induced Obese Rats\u003c/h2\u003e \u003cdiv id=\"Sec27\" class=\"Section4\"\u003e \u003ch2\u003eEffect of Ber/Gu-AGNCs on body weight, waist circumference (WC) and body mass index (BMI)\u003c/h2\u003e \u003cp\u003eHFD significantly increased body weight (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), WC (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and BMI (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) of rats at 1st week of its administration and this increase continued up to the 12th week (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). These results are substantiated by a previous study [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. The obese rats treated with standard drug (orlistat), berberine (10 mg/kg), Ber/Gu-AGNCs (10 and 20 mg/kg) and Gu-AGNCs (blank) once daily for 6 weeks (from 6th to 12th week) significantly decreased body weight (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, respectively) and WC (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, respectively) from 7th week onwards in comparison to HFD control rats. Orlistat, berberine (10 mg/kg) and Ber/Gu-AGNCs (10 and 20 mg/kg) also significantly decreased BMI (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, respectively) of obese rats from 7th week onwards in contrast to HFD control rats. However, Gu-AGNCs did not show a significant effect on BMI of rats at 7th and 8th week of their administration. Gu-AGNCs significantly decreased BMI of obese rats from the 9th week onwards as compared to HFD control rats. Moreover, Ber/Gu-AGNCs (10 and 20 mg/kg) displayed a significant decrease in body weight and BMI of obese rats in comparison to rats treated with Gu-AGNCs, indicating a better effect of Ber/Gu-AGNCs than Gu-AGNCs. In addition, 10 mg/kg dose of Ber/Gu-AGNCs also showed a significant decrease in body weight and BMI of obese rats in comparison to obese rats treated with free berberine (10 mg/kg). Ber/Gu-AGNCs did not show a significant decrease in WC in comparison to free berberine and Gu-AGNCs (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The decrease in body weight by berberine is also substantiated by an earlier study [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Effect of orlistat in decreasing body weight, WC and BMI is consistent with a reported study [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. The effect of guar gum and gum acacia in decreasing body weight in high fat diet-fed obese rats has been revealed in an earlier study [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Thereby, Ber/Gu-AGNCs showed better effects in decreasing body weight, WC and BMI than free berberine and Gu-AGNCs.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEffect of Ber/Gu-AGNCs on body weight of HFD-induced obese rats\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBody weight (g)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeeks\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHFD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Orlistat\u003c/p\u003e \u003cp\u003e(20 mg/kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Ber\u003c/p\u003e \u003cp\u003e(10 mg/kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Ber/Gu-AGNCs\u003c/p\u003e \u003cp\u003e(10 mg/kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Ber/Gu-AGNCs (20 mg/kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Gu-AGNCs\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e130.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e131.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e131.94\u0026thinsp;\u0026plusmn;\u0026thinsp;1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e130.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e131.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e129.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e130.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e131.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e137.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.86\u003csup\u003eaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e137.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e136.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e136.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e136.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e137.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e133.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e145.70\u0026thinsp;\u0026plusmn;\u0026thinsp;1.74\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e146.52\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e146.30\u0026thinsp;\u0026plusmn;\u0026thinsp;1.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e146.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e146.75\u0026thinsp;\u0026plusmn;\u0026thinsp;1.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e145.53\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e135.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e154.98\u0026thinsp;\u0026plusmn;\u0026thinsp;1.27\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e154.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e153.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e153.25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e154.36\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e154.43\u0026thinsp;\u0026plusmn;\u0026thinsp;1.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e135.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e166.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.87\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e166.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e166.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e166.97\u0026thinsp;\u0026plusmn;\u0026thinsp;1.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e167.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e167.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e138.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e177.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e177.69\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e177.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e177.27\u0026thinsp;\u0026plusmn;\u0026thinsp;1.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e178.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e177.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e142.77\u0026thinsp;\u0026plusmn;\u0026thinsp;1.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e189.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e189.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e189.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e189.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e189.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e189.15\u0026thinsp;\u0026plusmn;\u0026thinsp;1.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e148.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e202.44\u0026thinsp;\u0026plusmn;\u0026thinsp;1.28\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e193.27\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e198.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e195.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26\u003csup\u003ebbb***#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e194.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.65\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e200.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e152.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e210.92\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e198.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e203.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e200.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003csup\u003ebbb***#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e198.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e206.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e157.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e223.93\u0026thinsp;\u0026plusmn;\u0026thinsp;1.37\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e202.32\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e213.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e208.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003csup\u003ebbb***#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e205.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e216.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e162.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e234.10\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e206.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e222.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e215.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003csup\u003ebbb***###\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e212.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e225.59\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e11\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e168.83\u0026thinsp;\u0026plusmn;\u0026thinsp;1.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e245.28\u0026thinsp;\u0026plusmn;\u0026thinsp;1.17\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e213.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1.57\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e229.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e224.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003csup\u003ebbb***#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e218.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e235.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e12\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e172.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e254.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e216.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.24\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e237.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e230.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003csup\u003ebbb***###\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e224.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e243.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eValues are represented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM. Data were analyzed by one-way ANOVA followed by Tukey\u0026rsquo;s multiple comparison test (n\u0026thinsp;=\u0026thinsp;6 each group). \u003csup\u003eaa\u003c/sup\u003ep \u0026lt; 0.01, \u003csup\u003eaaa\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs.\u003c/em\u003e NC group; \u003csup\u003ebbb\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs.\u003c/em\u003e HFD group; ***p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 \u003cem\u003evs.\u003c/em\u003e HFD\u0026thinsp;+\u0026thinsp;Gu-AGNCs, \u003csup\u003e#\u003c/sup\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05, \u003csup\u003e###\u003c/sup\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001 \u003cem\u003evs.\u003c/em\u003e HFD\u0026thinsp;+\u0026thinsp;berberine\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eNC: Normal control, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes, HFD: High fat diet\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEffect of Ber/Gu-AGNCs on Waist circumference (WC) of HFD-induced obese rats\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWC (cm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeeks\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHFD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Orlistat\u003c/p\u003e \u003cp\u003e(20 mg/kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Berberine\u003c/p\u003e \u003cp\u003e(10 mg/kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Ber/Gu-AGNCs\u003c/p\u003e \u003cp\u003e(10 mg/kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Ber/Gu-AGNCs (20 mg/kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Gu-AGNCs\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e11.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e11.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e11.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e12.46\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e13.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e12.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.80\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e13.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e13.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e13.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e15.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e14.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.46\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003csup\u003ebb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003csup\u003ebb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003ebb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e15.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e14.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.46\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16.46\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e15.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e17.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e16.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e18.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e18.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e11\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e16.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e18.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e19.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e12\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e17.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.46\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e19.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e20.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eValues are represented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM. Data were analyzed by one-way ANOVA followed by Tukey\u0026rsquo;s multiple comparison test (n\u0026thinsp;=\u0026thinsp;6 each group). \u003csup\u003ea\u003c/sup\u003ep \u0026lt; 0.05, \u003csup\u003eaaa\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs.\u003c/em\u003e NC group; \u003csup\u003eb\u003c/sup\u003ep \u0026lt; 0.05,\u003csup\u003ebb\u003c/sup\u003ep \u0026lt; 0.05,\u003csup\u003ebbb\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs.\u003c/em\u003e HFD group\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eNC: Normal control, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes, HFD: High fat diet\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEffect of Ber/Gu-AGNCs on BMI in HFD-induced obese rats\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBMI (g/cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeeks\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHFD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Orlistat (20 mg/kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Berberine\u003c/p\u003e \u003cp\u003e(10 mg/kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Ber/Gu-AGNCs\u003c/p\u003e \u003cp\u003e(10 mg/kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Ber/Gu-AGNCs\u003c/p\u003e \u003cp\u003e(20 mg/kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHFD\u0026thinsp;+\u0026thinsp;Gu-AGNCs\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.361\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.363\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.361\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.360\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.361\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.357\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.361\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.361\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.374\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.373\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.374\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.371\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.372\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.375\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.365\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.391\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.393\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.392\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.393\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.393\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.389\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.371\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.416\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.412\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.411\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.410\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.411\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.413\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.372\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.433\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.435\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.433\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.437\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.439\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.439\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.373\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.458\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.460\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.459\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.459\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.463\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.458\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.375\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.475\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.482\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.478\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.476\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.478\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.476\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.387\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.503\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0008\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.488\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.495\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0004\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.487\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0006\u003csup\u003ebbb***#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.489\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.500\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003ens\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.393\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.516\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.493\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.503\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0008\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.494\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0004\u003csup\u003ebbb***#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.493\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.510\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003ens\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.394\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.532\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.499\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.517\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0009\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.506\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0004\u003csup\u003ebbb**ns\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.504\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003csup\u003ebbb**\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.522\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.401\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.552\u0026thinsp;\u0026plusmn;\u0026thinsp;0.009\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.501\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.526\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.513\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003ebbb***#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.511\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.533\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e11\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.406\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.566\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.502\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.537\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.524\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003csup\u003ebbb***#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.513\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.549\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003ebb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e12\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.407\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.573\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.503\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.538\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.531\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0005\u003csup\u003ebbb***#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.516\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.550\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eValues are represented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM. Data were analyzed by one-way ANOVA followed by Tukey\u0026rsquo;s multiple comparison test (n\u0026thinsp;=\u0026thinsp;6 each group). \u003csup\u003ea\u003c/sup\u003ep \u0026lt; 0.05, \u003csup\u003eaaa\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs.\u003c/em\u003e NC group; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, \u003csup\u003ebb\u003c/sup\u003ep \u0026lt; 0.001, \u003csup\u003ebbb\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs.\u003c/em\u003e HFD group. **p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, ***p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 \u003cem\u003evs.\u003c/em\u003e HFD\u0026thinsp;+\u0026thinsp;Gu-AGNCs; \u003csup\u003e#\u003c/sup\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.01 \u003cem\u003evs.\u003c/em\u003e HFD\u0026thinsp;+\u0026thinsp;berberine\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eNC: Normal control, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes, HFD: High fat diet, ns: non significant\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec28\" class=\"Section2\"\u003e \u003ch2\u003eInsert Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e here\u003c/h2\u003e \u003cdiv id=\"Sec29\" class=\"Section3\"\u003e \u003ch2\u003eEffect of Ber/Gu-AGNCs on food intake\u003c/h2\u003e \u003cp\u003eNo significant difference was observed in daily intake of food by rats of all the groups (Data not shown).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eEffect of Ber/Gu-AGNCs on liver weight, adipose tissue weight, liver index and adiposity index\u003c/h3\u003e\n\u003cp\u003eLiver is a metabolizing organ that is liable to fat deposition and hence, excessive accumulation of fat resulted in significant increase in liver weight [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. In our study, liver weight, liver index, adipose tissue weight and adiposity index were significantly higher in the HFD treated control rats. HFD treated rats showed significant increase in liver weight, liver index (%), adipose tissue weight and adiposity index (%) on 85th day in comparison to normal control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Oral treatment with orlistat (20 mg/kg), berberine (10 mg/kg), Ber/Gu-AGNCs (10 and 20 mg/kg) and Gu-AGNCs (blank) once daily for 6 consecutive weeks (from 7th week to 12th week) significantly reversed HFD-induced increase of liver weight (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all the five treatments), liver index (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 respectively), adipose tissue weight (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all the five treatments) and adiposity index (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 respectively). Furthermore, Ber/Gu-AGNCs (10 and 20 mg/kg) showed a significant reversal of these parameters in comparison to Gu-AGNCs. In addition, 10 mg/kg dose of Ber/Gu-AGNCs also showed significant reversal of liver weight (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), liver index (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), total adipose weight (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and adiposity index (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in comparison to free berberine (10 mg/kg), indicating better effect of Ber/Gu-AGNCs than free berberine (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The decrease in liver weight by berberine is consistent with a previous study [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. The role of guar gum in lowering liver weight and adipose tissue weight has been described in a previous study [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Hence, Ber/Gu-AGNCs showed a better effect in lowering liver weight, adipose tissue weight, liver index and adiposity index than free berberine and Gu-AGNCs.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEffect of Ber/Gu-AGNCs on liver weight, liver index, adipose tissue weight and adiposity index in HFD-induced obese rats on 85th day\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLiver weight (g)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLiver index (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal adipose tissue weight (g)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAdiposity index (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;orlistat\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.019\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Ber\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Ber/Gu-AGNCs (10 mg/kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003csup\u003ebbb***###\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ebbb***#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ebbb***###\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.007\u003csup\u003ebbb***#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Ber/Gu-AGNCs (20 mg/kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Gu-AGNCs\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.46\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.008\u003csup\u003ebb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eValues are represented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM. Data were analyzed by one-way ANOVA followed by Tukey\u0026rsquo;s multiple comparison test (n\u0026thinsp;=\u0026thinsp;6 each group). \u003csup\u003eaaa\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs.\u003c/em\u003e NC group; \u003csup\u003eb\u003c/sup\u003ep \u0026lt; 0.05, \u003csup\u003ebb\u003c/sup\u003ep \u0026lt; 0.05, \u003csup\u003ebbb\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs.\u003c/em\u003e HFD group; ***p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 \u003cem\u003evs.\u003c/em\u003e HFD\u0026thinsp;+\u0026thinsp;Gu-AGNCs; \u003csup\u003e#\u003c/sup\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05, \u003csup\u003e###\u003c/sup\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003cem\u003evs.\u003c/em\u003e HFD\u0026thinsp;+\u0026thinsp;berberine\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNC: Normal control, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes, HFD: High fat diet\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eInsert\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e \u003cb\u003ehere\u003c/b\u003e\u003c/p\u003e \u003cdiv id=\"Sec31\" class=\"Section2\"\u003e \u003ch2\u003eEffect of Ber/Gu-AGNCs on Serum lipid profile and atherogenic index (AI)\u003c/h2\u003e \u003cp\u003eSerum levels of TC, TG, LDL-c, VLDL-c; and atherogenic index increased significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), but HDL-c levels decreased significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in HFD treated rats in comparison to normal control rats. Oral treatment with orlistat (20 mg/kg), berberine (10 mg/kg), Ber/Gu-AGNCs (10 and 20 mg/kg) and Gu-AGNCs significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) reversed HFD-induced increase of TC, TG, LDL-c, VLDL-c levels, and atherogenic index; and also significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) reversed HFD-induced decrease of HDL-c. Ber/Gu-AGNCs (10 and 20 mg/kg) significantly decreased TC (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), TG (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), LDL-c (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), VLDL-c (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) levels; and atherogenic index (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) when compared to Gu-AGNCs. Moreover, Ber/Gu-AGNCs (10 mg/kg) significantly decreased TC (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), TG (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), LDL-c (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), VLDL-c (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) levels; and atherogenic index (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) when compared to free berberine (10 mg/kg) [Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e]. The lipid lowering effect of free berberine is also substantiated with an earlier study [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. The lipid lowering effect of guar gum and gum acacia has also been described in a previous study [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. Hence, Ber/Gu-AGNCs showed a better anti-hyperlipidemic effect than free berberine and Gu-AGNCs.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEffect of Ber/Gu-AGNCs on serum TC, TG, HDL-c, LDL-c, VLDL-c levels and atherogenic index in HFD-induced obese rats on 85th day\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLipid levels (mg/dl)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTG\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHDL-c\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLDL-c\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVLDL-c\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAI\u003c/p\u003e \u003cp\u003e(TG/HDL)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e136.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e91.20\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Orlistat\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(20 mg/kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.02\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Ber\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(10 mg/kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e107.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e59.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Ber/Gu-AGNCs\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(10 mg/kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54\u003csup\u003ebbb***###\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003csup\u003ebbb***###\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003csup\u003ebbb***###\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003csup\u003ebbb***###\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003csup\u003ebbb***###\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ebbb***###\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Ber/Gu-AGNCs\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(20 mg/kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.65\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Gu-AGNCs\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e122.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e109.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eValues are represented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM. Data were analyzed by one-way ANOVA followed by Tukey\u0026rsquo;s multiple comparison test (n\u0026thinsp;=\u0026thinsp;6 each group). \u003csup\u003eaaa\u003c/sup\u003ep \u0026lt; 0.001\u003cem\u003evs.\u003c/em\u003e NC group. \u003csup\u003ebbb\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs.\u003c/em\u003e HFD group; ***p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 \u003cem\u003evs.\u003c/em\u003e Gu-AGNCs; \u003csup\u003e###\u003c/sup\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001 \u003cem\u003evs.\u003c/em\u003e berberine. TC- total cholesterol, TG - total triglycerides, HDL-c \u0026ndash; high-density lipoprotein-cholesterol, LDL-c - low-density lipoprotein-cholesterol, VLDL-c \u0026ndash; very-low density lipoprotein-cholesterol\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eNC: Normal control, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes, HFD: High fat diet\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eInsert\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e \u003cb\u003ehere\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec32\" class=\"Section2\"\u003e \u003ch2\u003eEffect of Ber/Gu-AGNCs on liver enzymes (SGOT and SGPT)\u003c/h2\u003e \u003cp\u003eSGOT and SGPT are the most important liver biomarkers enzymes and their elevated level in serum indicates hepatocyte damage [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. The levels of these enzymes were significantly higher in HFD treated rats than in normal control rats. These results are in agreement with earlier studies [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. SGOT and SGPT were significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) elevated in HFD treated rats in comparison to normal control rats. Oral treatment with orlistat (20 mg/kg), berberine (10 mg/kg), Ber/Gu-AGNCs (10 mg/kg and 20 mg/kg) and Gu-AGNCs (blank) significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) reversed HFD-induced increase of SGOT and SGPT levels. Moreover, Ber/Gu-AGNCs (10 and 20 mg/kg) also showed significant decrease of SGOT (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and SGPT (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) levels as compared to Gu-AGNCs, indicating potentiation of hepatoprotective effect of Gu-AGNCs. Also, Ber/Gu-AGNCs (10 mg/kg) showed significant decrease of SGOT (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and SGPT (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) as compared to free berberine (10 mg/kg) [Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e]. The effect of berberine in decreasing SGOT and SGPT levels is reported by an earlier study [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. The hepatoprotective effect of gum acacia against CCl\u003csub\u003e4\u003c/sub\u003e-induced hepatotoxicity has been described in an earlier study [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. Hence, Ber/Gu-AGNCs displayed a better hepatoprotective effect than free berberine and Gu-AGNCs.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEffect of Ber/Gu-AGNCs on SGOT and SGPT levels in HFD-induced obese rats on 85th day\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSGOT (U/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSGPT (U/L)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e125.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.17\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u003csup\u003eaaa\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Orlistat (20 mg/kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63.80\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Ber (10 mg/kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.36\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Ber/Gu-AGNCs (10 mg/kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003csup\u003ebbb***###\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51\u003csup\u003ebbb***###\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Ber/Gu-AGNCs (20mg/kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.80\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003csup\u003ebbb***\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFD\u0026thinsp;+\u0026thinsp;Gu-AGNCs\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99.46\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.48\u0026thinsp;\u0026plusmn;\u0026thinsp;049\u003csup\u003ebbb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eValues are represented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM. Data were analyzed by one-way ANOVA followed by Tukey\u0026rsquo;s multiple comparison test (n\u0026thinsp;=\u0026thinsp;6 each group). \u003csup\u003eaaa\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs\u003c/em\u003e NC; \u003csup\u003ebbb\u003c/sup\u003ep \u0026lt; 0.001 \u003cem\u003evs.\u003c/em\u003e HFD group;***p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 \u003cem\u003evs.\u003c/em\u003e HFD\u0026thinsp;+\u0026thinsp;Gu-AGNCs; \u003csup\u003e###\u003c/sup\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001 \u003cem\u003ev\u003c/em\u003es. HFD\u0026thinsp;+\u0026thinsp;berberine\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eNC: Normal control, Ber/Gu-AGNCs: Berberine loaded guar-acacia gum nanocomplexes, Gu-AGNCs: Guar-acacia gum nanocomplexes, HFD: High fat diet\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eInsert\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e \u003cb\u003ehere\u003c/b\u003e\u003c/p\u003e \u003cdiv id=\"Sec33\" class=\"Section3\"\u003e \u003ch2\u003eEffect of Ber/Gu-AGNCs on liver catalase, reduced glutathione (GSH) and malondialdehyde (MDA) levels\u003c/h2\u003e \u003cp\u003eHigh fat diet treated rats showed significant increase of MDA levels, and decrease in catalase activity and GSH levels in contrast to normal control rats, indicating induction of oxidative stress. These findings are also supported by an earlier study [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. MDA is a product of lipid peroxidation, which is a marker for oxidative stress. In liver tissues, increased accumulation of fat leads to the production of large free radicals which in turns leads to lipid peroxidation and oxidative stress [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. Catalase and GSH play an important roles in antioxidant defense processes [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. The hepatic activities of catalase and reduced glutathione were significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) decreased while the level of MDA was significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) increased in HFD treated rats in comparison to normal control rats. Oral treatment with orlistat (20 mg/kg), berberine (10 mg/kg), Ber/Gu-AGNCs (10 and 20 mg/kg) and Gu-AGNCs (blank) significantly reversed HFD-induced decrease of catalase (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 respectively) and GSH activities (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all the five treatments), and also significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all the five treatments) reversed HFD-induced increase of MDA level. Ber/Gu-AGNCs (10 and 20 mg/kg) also significantly increased catalase (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and GSH (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) activities; and decreased MDA levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in comparison to Gu-AGNCs. Moreover, Ber/Gu-AGNCs (10 mg/kg) exhibited a significant increase of catalase (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and GSH (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) activities; and decrease of MDA level (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) as compared to free berberine (10 mg/kg) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea, b and c). Berberine has been reported to attenuate oxidative stress in rats with non-alcoholic fatty liver disease [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. The role of gum acacia and guar gum in decreasing markers of oxidative stress in the liver of high fat diet-induced obese mice and high fat diet-fed hamsters respectively has been described in an earlier study [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e, \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. Hence, Ber/Gu-AGNCs showed better oxidative stress ameliorating effect than free berberine and Gu-AGNCs.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec34\" class=\"Section3\"\u003e \u003ch2\u003eInsert Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea,b, c here\u003c/h2\u003e \u003cdiv id=\"Sec35\" class=\"Section4\"\u003e \u003ch2\u003eEffects of Ber/Gu-AGNCs on blood glucose level on 85th day\u003c/h2\u003e \u003cp\u003eHFD treated rats showed significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) increase in blood glucose level on 85th day in comparison to normal control group. Oral treatment with orlistat (20 mg/kg), berberine (10 mg/kg), Ber/Gu-AGNCs (10 and 20 mg/kg) and Gu-AGNCs once daily for 6 consecutive weeks (from 7th week to 12th week) significantly decreased (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) blood glucose level in comparison to HFD treated control group. Ber/Gu-AGNCs (10 and 20 mg/kg) also showed significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) decrease in blood glucose level as compared to Gu-AGNCs (blank). In addition, 10 mg/kg dose of Ber/Gu-AGNCs also displayed significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) decrease in blood glucose levels in comparison to free berberine (10 mg/kg) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Berberine decreased blood glucose level in obese rats is also supported by an earlier study [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. The effect of gum acacia and guar gum in decreasing blood glucose levels has been described in an earlier study [\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Hence, Ber/Gu-AGNCs showed better glucose lowering effect than free berberine and Gu-AGNCs.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eInsert\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cb\u003ehere\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eHistopathological studies\u003c/h3\u003e\n\u003cp\u003eMicroscopic evaluation of liver of normal control rat (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea) revealed normal histological hepatic architecture arranged as cords of hepatocytes with central vein and portal triads without any pathological alterations. Micrograph of liver of rat fed with HFD showed hepatosteatosis characterized by fatty vacuolar degenerative changes in hepatic cells and formation of fatty cysts in hepatic parenchyma (Fig.\u0026nbsp;3b2), sinusoidal dilatation, congestion of central veins and focal area of hepatic necrosis characterized by inflammatory cell infiltration (Fig.\u0026nbsp;3b1). These results are substantiated by an earlier study [\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e]. HFD\u0026thinsp;+\u0026thinsp;Gu-AGNCs treated rat also showed congestion of central veins and sinusoidal dilatation but focal area of hepatic necrosis was not observed, indicating some amount of hepatoprotective effect (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eg). The decrease in hepatocyte degeneration by gum acacia in the histological analysis of liver tissue has been described in an earlier study [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. Rat treated with HFD along with orlistat showed almost normal histological architecture as evident by less lipid droplets accumulation, no necrosis and inflammatory reaction (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec).The liver of berberine-treated rat showed improvement as revealed by less dilatation of sinusoids and decreased number of lipid droplets (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed). The observed results with berberine were substantiated by an earlier reported study [\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e]. In contrast, rats treated with Ber/Gu-AGNCs showed better improvement as central vein appeared normal, no appearance of dilated sinusoids and very few lipid droplets in lower dose group (10 mg/kg) and almost absence of lipid droplets in high dose group (20 mg/kg) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ee and f).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eInsert\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e \u003cb\u003ehere (a-g)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn histological micrograph of adipose tissue, there was hypertrophy (increased size) of retroperitoneal adipocytes in HFD treated rat (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb) as compared to normal control rat (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea). These findings are agreeing with a previous study [\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e]. However, the rat treated with orlistat showed significant decrease in size of adipocytes (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ec). Berberine\u0026thinsp;+\u0026thinsp;HFD treated rat (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ed) revealed decrease in size of adipocytes as compared to HFD treated rat. These results are substantiated by an earlier study [\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e]. Ber/Gu-AGNCs (10 and 20 mg/kg)\u0026thinsp;+\u0026thinsp;HFD treated rat also showed marked decrease in size of adipocytes (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ee and f). Gu-AGNCs (blank)\u0026thinsp;+\u0026thinsp;HFD treated rat (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eg) showed only mild decrease in size of adipocytes in comparison to HFD treated rat. Hence, Ber/Gu-AGNCs showed better improvement in comparison to Gu-AGNCs and free berberine\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eInsert\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e \u003cb\u003ehere (4a-g)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe better anti-obesity activity of Ber/Gu-AGNCs in comparison to free berberine and Gu-AGNCs (blank) in the above studied parameters might be due to improvement in bioavailability, solubility and stability of berberine after encapsulation within polymeric nanoparticles. These results are substantiated by an earlier study where nanoencapsulation improved solubility and stability of \u003cem\u003etrans\u003c/em\u003e-Resveratrol, and thereby their anti-obesity activity [\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e]. Similarly, Zhang et al (2013) reported enhanced anti-obesity activity of epigallocatechin gallate by nanoencapsulation [\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e]. In addition, guar gum and gum acacia possesses significant anti-obesity activity. So, the anti-obesity properties of gums may add a synergistic effect in berberine nanoformulation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn the current work, berberine loaded guar-acacia gum nanocomplexes (Ber/Gu-AGNCs) were successfully prepared \u003cem\u003evia\u003c/em\u003e ionic complexation method using guar gum and gum acacia as nanocarriers. The nanocomplexes exhibited a homogenous morphological structure, appropriate diameter, good zeta potential and excellent encapsulation efficiency. \u003cem\u003eIn vivo\u003c/em\u003e studies in high-fat diet induced obesity model in rats showed better anti-obesity effect of Ber/Gu-AGNCs (10 and 20 mg/kg) than free berberine and blank nanocomplexes. Further studies can be carried out to explore the other possible mechanisms for better anti-obesity effect of Ber/Gu-AGNCs. Moreover, the study can also be extended clinically for better management of obesity with Ber/Gu-AGNCs.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003cstrong\u003eata availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data provided in this manuscript is new and has not published elsewhere. This data includes figures (images), and tables. The data generated during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors\u0026nbsp;acknowledge Guru Jambheshwar University\u0026nbsp;of\u0026nbsp;Science \u0026amp; Technology, (Hisar), for the financial support in the form of University Research Fellowship (URF)\u0026nbsp;(Endst.No.Sch \u0026amp; SC/ST/20/626-632);\u0026nbsp;Sophisticated Analytical Instrumentation Facility (SAIF), AIIMS, New Delhi and Luvas (Hisar) for providing facilities\u0026nbsp;for carrying out this research work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis\u0026nbsp;study\u0026nbsp;was funded by Guru Jambheshwar University\u0026nbsp;of\u0026nbsp;Science \u0026amp; Technology, Hisar\u0026nbsp;for the\u0026nbsp;University Research Fellowship (URF)\u0026nbsp;(Grant Agreement No. Endst.No.Sch \u0026amp; SC/ST/20/626-632).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors and Affiliations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDepartment of Bio \u0026amp; Nano Technology, Guru Jambheshwar University of Science \u0026amp; Technology, Hisar\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e125001\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eIndia\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJyoti Bakshi, Assim Verma, Sapna Grewal\u0026nbsp;\u0026amp;\u0026nbsp;Santosh Kumari\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDepartment of Pharmaceutical Sciences, Guru Jambheshwar University of Science \u0026amp; Technology, Hisar\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e125001\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eIndia\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrity Lathar\u0026nbsp;and\u0026nbsp;Dinesh Dhingra\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDepartment of Veterinary Pathology, Lala Lajpat Rai University of Veterinary \u0026amp; Animal\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSci\u003c/strong\u003e\u003cstrong\u003eences,\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Hisar\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e125001\u003c/strong\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eIndia \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDeepika Lather\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003cstrong\u003es\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSK: conceptualization. SK and DD: methodology. JB: formal analysis and investigation. JB, DD and DL: writing original draft preparation. DD, SG, PL and AV: Funding acquisition. DD and PL: \u0026nbsp; Resources. JB, SK and DD: supervision.\u0026nbsp;All the authors\u0026nbsp;have checked the manuscript and\u0026nbsp;have agreed to the submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWistar albino female rats (body weight 130-140 g; 4-6 months old) were procured from Experimental Animal Facility, Guru Jambheshwar University of Science and Technology, Hisar (Haryana, India). The number of animals\u0026nbsp;use\u0026nbsp;in this research study and experimental protocol were approved by Institutional Animal Ethics Committee (IAEC) in its meeting held on 10\u003csup\u003eth\u003c/sup\u003e Feb., 2022 [IAEC minutes letter No. IAEC/2022/10-18, dated 22-2-2022].\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eP.G. Kopelman, Nature (2000) \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/35007508\u003c/span\u003e\u003cspan address=\"10.1038/35007508\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJ.T. Dipiro, R.L. Talbert, G.C. Yee, G.R. Matzke, B.G. Wells, L.M. Posey, Pharmacotherapy: A Pathophysiologic Approach, 6th edn. (The McGraw-Hill Companies, New York, 2005) pp. 2662\u0026ndash;2670\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eK.M. Flegal, B.L. 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Wang, J Agric Food Chem (2013) \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1021/jf4023004\u003c/span\u003e\u003cspan address=\"10.1021/jf4023004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Berberine, Nanoencapsulation, High fat diet, Anti-obesity, Guar gum, Gum acacia","lastPublishedDoi":"10.21203/rs.3.rs-3928032/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3928032/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBerberine is a promising bioactive compound that has gained great attention against numerous diseases but its low solubility and poor systemic bioavailability hinders its clinical applicability. Therefore, this study attempted to enhance the therapeutic potential of berberine by its nanoencapsulation. Berberine loaded guar-acacia gum nanocomplexes (Ber/Gu-AGNCs) were prepared by ionic complexation method; characterized and evaluated for anti-obesity activity in high fat diet (HFD) induced obese rats. HFD was given to animals for 6 consecutive weeks. Orlistat (20 mg/kg, p.o.), berberine (10 mg/kg), Ber/Gu-AGNCs (10 and 20 mg/kg, p.o) and Gu-AGNCs (blank) were administered once a day after giving HFD for 6 weeks; and continued up to 12 weeks along with HFD. Obesity was evaluated by the measurement of morphological parameters, blood glucose, serum lipid profiles, liver enzymes and levels of oxidative stress markers. Moreover, histopathological studies of liver and adipose tissue were also carried out. The results showed that Ber/Gu-AGNCs exhibited spherical morphology and narrow size distribution. In addition, Ber/Gu-AGNCs were significantly more effective in controlling the body weight, BMI, adiposity index, liver index, blood glucose levels, serum lipids and oxidative stress levels in comparison to berberine in HFD-induced obese rats. Furthermore, histopathological examination of liver and adipose tissue revealed the anti-obesity effect of Ber/Gu-AGNCs (10 and 20 mg/kg), as indicated by decrease in hepatosteatosis and inflammation in liver tissue; and decrease in the size of adipocytes in fat depots. Thus, nanoencapsulation of berberine into gum nanocomplexes displayed better anti-obesity activity when compared to free berberine.\u003c/p\u003e","manuscriptTitle":"Potentiation of anti-obesity activity of berberine through its encapsulation in guar-acacia gum nanocomplexes in Wistar albino rats","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-15 14:54:01","doi":"10.21203/rs.3.rs-3928032/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"650f1d19-bfcd-4ab6-9521-6bdfe54eaa73","owner":[],"postedDate":"February 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-02T08:32:25+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-15 14:54:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3928032","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3928032","identity":"rs-3928032","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}