Phytochemical Profiling and Antidiabetic Activity of Algerian Medicinal Plants: In Vitro α-Amylase Inhibition and In Vivo Glucose-Lowering Effects

preprint OA: closed
Full text JSON View at publisher
Full text 153,683 characters · extracted from preprint-html · click to expand
Phytochemical Profiling and Antidiabetic Activity of Algerian Medicinal Plants: In Vitro α-Amylase Inhibition and In Vivo Glucose-Lowering Effects | 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 Article Phytochemical Profiling and Antidiabetic Activity of Algerian Medicinal Plants: In Vitro α-Amylase Inhibition and In Vivo Glucose-Lowering Effects Lilya Harchaoui, Saida Ouafi, Wafa Zahnit, Mohammed Messaoudi, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9172706/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Various phytotherapeutic compounds with hypoglycemic properties offer a promising avenue to combat diabetes and its associated complications. This study was carried out to investigate the in vivo and in vitro antidiabetic activity and bioactive compounds of Salvia verbenaca , Ferula vesceritensis Coss & Dur., and Myrtus communis L., which are used in Algerian traditional medicine. The in vivo antidiabetic assays of infusion extracts of the three plants at 100 and 500 mg/kg b.w, were performed using a hypoglycemic study in normal mice, an oral glucose tolerance test, and streptozotocin-induced diabetic mice. The α-amylase inhibitory test was used to determine the in vitro antidiabetic activity. Phytochemical composition and bioactive profiling were determined using HPLC analysis. The findings indicated a general agreement between in vivo and in vitro antidiabetic effects, rather than a direct quantitative correlation. In the in vivo antidiabetic activities, the infusion extract of F. vesceritensis displayed significantly (P<0.05) higher potency in reducing glycemia, glucose load–induced hyperglycemia, and in alleviating streptozotocin-induced diabetes, highlighting its potential as a source of bioactive compounds for therapeutic applications, with effects comparable to or higher than metformin under the tested conditions. S. verbenaca infusion extract showed a comparable blood glucose reduction to the reference drug. Similar findings were obtained in the α-amylase inhibitory test, where the infusion extract of F. vesceritensis showed strong inhibitory activity, while S. verbenaca also exhibited comparable inhibitory effects relative to the reference under the tested conditions. The phytochemical analysis revealed the presence of rutin and kaempferol in F. vesceritensis and S. verbenaca infusion extracts, and their absence in M. communis infusion extract, which may explain their observed bioactivity and supports their relevance as natural products with antidiabetic potential. However, further in vivo and clinical studies are required to confirm these findings and their translational relevance. Biological sciences/Biochemistry Biological sciences/Drug discovery Health sciences/Medical research Biological sciences/Plant sciences Diabetes medicinal plants streptozotocin antidiabetic activity α-amylase Figures Figure 1 Figure 2 Figure 3 1. Introduction Diabetes mellitus, characterized by chronic hyperglycemia, is a global health concern with an increasing prevalence across various populations [ 1 ]. Its impact on individuals, such as reduced treatment effectiveness and increased adverse effects and the burden it places on healthcare systems have spurred extensive research into novel approaches for its prevention and management. There is growing interest in exploring alternative, complementary, and natural sources for effective antidiabetic treatments [ 2 ]. The search for new and more sustainable treatments has led to the investigation of medicinal plants as sources of bioactive compounds with therapeutic potential. Globally, medicinal plants have served as an essential therapeutic resource, with over half of the global population relying on these plants, using extracts or active components as a traditional medicine to meet their fundamental healthcare needs [ 3 ]. These plants have shown potential in reducing blood glucose levels and mitigating the complications associated with diabetes [ 4 , 5 ]. These plants have been traditionally used by local healers, and understanding their use through ethnopharmacological approaches is crucial to validate indigenous medical practices. Algeria possesses an important reservoir of medicinal plants owing to its rich biodiversity. In the southern regions of the nation, indigenous communities continue to depend on traditional healers for addressing various health concerns such as diabetes [ 6 ]. Among the medicinal plants used in Algerian herbal medicine for the treatment of diabetes are Salvia verbenaca , Ferula vesceritensis Coss & Dur. and Myrtus communis L. Ferula vesceritensis Coss & Dur. is among the six species belonging to the Ferula genus in Algeria; this specie is abundant in south east of the country [ 7 ]. The aerial part of this plant is used in traditional medicine to treat headaches, fever, and throat infections [ 7 ]. In Algeria Sahara, the genus Salvia is represented by three species, including Salvia verbenaca subsp. clandestina (L.) Batt. [ 8 ]. Various traditional applications of this plant have been documented, such as reducing fever, easing digestive and spasmodic pain, and addressing liver disorders [ 9 ]. Myrtus communis L known as true myrtle, is a medicinal plant native to the Mediterranean area and belongs to the Myrtaceae family [ 10 ]. According to traditional medicine data, myrtle has been widely used for the treatment of various ailments, including pulmonary diseases, and viral and bacterial infections [ 11 ]. Ethnobotanical investigation indicates that these plants are widely used for reducing blood sugar levels [ 12 – 14 ]. However, to date, no scientific studies have comprehensively evaluated the bioactive compounds and their in vitro and in vivo antidiabetic activities. To our knowledge, this is the first comprehensive study integrating phytochemical profiling with in vitro and in vivo biological evaluation for these three medicinal plants used in Algerian traditional medicine. The aim of this study was to evaluate antidiabetic activities of Salvia verbenaca , Ferula vesceritensis Coss & Dur. and Myrtus communis L through in vivo and in vitro essays to verify the validity of their traditional use. Furthermore, a chromatographic phytochemical analysis was conducted to identify bioactive compounds potentially responsible for their antidiabetic activity. 2. Experimental 2.1. Plant Material The aerial parts of Salvia verbenaca and Ferula vesceritensis Coss & Dur. were collected from El atteuf in Ghardaia region 32° 28′ 60″ north, 3° 40′ 60″ east (northern Algerian Sahara). Myrtus communis L. aerial parts were gathered from Cherchell station 36° 36′ 27″ north, 2° 11′ 26″ east, a coastal town west of Algiers. The plants were identification by botanist, Prof. Saida Ouafi, according to Quezel and Santa [ 15 ]. Standard voucher specimens were conserved at the herbarium of Chemistry Department, University of Mentouri- Algeria ( Salvia verbenaca : Sv15/137, Ferula vesceritensis : Fv03/10 and Myrtus communis : Mc32/61). The harvested plant aerial parts were air-dried until completely dehydrated at room temperature. Subsequently, the desiccated samples were finely powdered using an electric blender and stored in paper bags until their use. 2.2. Animals Adult male albino mice, Mus musculus , weighing 20–25 g, were procured from the Pasteur Institute of Algeria. The animals were kept in a standard laboratory environment at a temperature of 24 ± 2˚C and a 12-hour light/dark cycle, with access to food and water provided ad libitum. The experimental procedures were approved by the ethical committee of the Algerian Association of Experimental Animal Sciences (88–08/1988) and conducted in adherence to the European Directive 2010/63/EU (EC, 2010) regarding the welfare of animals used for experimental and scientific purposes. The use of albino mice in the investigation of in vivo antidiabetic activity of plants infusion extracts was approved by the Ethical Committee of Animal Experimentation (CEEA) of University of Sciences and Technology Houari Boumediene (USTHB) with approved Ref N°: CEEA-USTHB-08-2023/11118, Algeria. 2.3. Plant extraction The infusion extract of each plant sample was prepared using a traditional technique according to the method of Kraft and Hobbs [ 16 ], involving the addition of boiling distilled water/saline solution to the sample (1 g per 50 mL). After allowing it to steep at room temperature for 10 minutes, the mixture was filtered using Whatman grade No. 1 filter paper. Thereafter, the infusion extract underwent lyophilization and was reconstituted in methanol for chromatographic analysis [ 17 ]. 2.4. In vivo antidiabetic assays 2.4.1. Grouping and dosing of animals In the context of Streptozotocin-induced diabetes and hypoglycemic and oral glucose tests, mice were randomized into eight groups of five mice each. As a negative control, Group I was administered a solution containing 10 mL per kg b.w. of distilled water. Metformin was administered to Group II (the positive control) at 500 mg per kg b.w. Salvia verbenaca infusion extract was administered at 100 and 500 mg per kg b.w. to Groups III and IV, respectively. Similarly, the subjects in groups V and VI were administered infusion extract of Ferula vesceritensis Coss & Dur. at respective concentrations of 100 and 500 mg/kg body weight. In conclusion, infusion extract of Myrtus communis L. was administered to Groups VII and VIII at concentrations of 500 mg per kg b.w. and 100 mg per kg b.w., respectively. 2.4.2. Measurement of blood glucose level Blood samples used for the blood glucose analysis were collected from the tail tip of each animal for all assessments. A blood glucometer (Accu Check Active, Roche, Germany) was employed to ascertain the blood glucose levels. 2.4.3. Hypoglycemic study in normal mice The hypoglycemic effect of infusion extracts from three species was investigated in non-diabetic mice. The animals underwent a 16-hour overnight fasting period before the commencement of the experiment. A glucometer determined the initial fasting blood sugar levels the subsequent morning at 0 h. Subsequently, the animals in their respective groups were orally administered distilled water, the infusion extracts of Salvia verbenaca , Ferula vesceritensis Coss & Dur., Myrtus communis L. (100 and 500 mg per kg b.w.) and the reference drug (Metformin 500 mg per kg b.w.). Blood glucose levels were subsequently measured at 1 hour, 3 hours, and 5 hours following the administration of the experimental medications in order to evaluate their hypoglycemic impact [ 18 ]. 2.4.4. Oral glucose tolerance test Oral glucose tolerance assay of infusion extracts of three plants was conducted in normal mice. After a 16-hour overnight fasting period, mice within their respective groups were orally administered various treatments: distilled water, infusion extracts of Salvia verbenaca , Ferula vesceritensis Coss & Dur., Myrtus communis L. (100 and 500 mg per kg b.w.), and the reference drug (Metformin 500 mg per kg b.w.). Thirty minutes following this administration, the animals were orally administered a 40% glucose solution (4 g/kg). Blood glucose levels were measured prior to the treatments (representing baseline fasting glucose levels) and at 30 min, 60 min, 90 min, and 120 min after the injection of glucose [ 19 ]. The percentage decrease in the level of blood glucose following 120 minutes was calculated using the following: % = ((Bgl 30 min - Blgl 120 min ) / Bgl 30 min ) × 100 [ 20 ] Bgl 30 min Blood glucose level after 30 min of glucose ingestion Blgl 120 min : Blood glucose level at t :120 min 2.4.5. Streptozotocin induced diabetes mice After an overnight fasting period for the animals, blood glucose levels were measured before inducing diabetes. Diabetes was induced experimentally by administering freshly prepared streptozotocin (STZ) through intraperitoneal injection (45 mg per kg in 0.1 M sodium citrate buffer, pH 4.5) [ 21 ]. Thirty minutes after the injection, mice were given unrestricted delivery of food and water. Animals' diabetes confirmation was based on elevated blood glucose levels observed after 72 hours post-injection; only mice with fasting blood glucose levels exceeding 2 g/L were included in the study [ 22 ]. Following this, mice in their designated groups received different oral treatments: buffer solution, infusion extracts of Salvia verbenaca , Ferula vesceritensis Coss & Dur., Myrtus communis L. at 1000 mg per kg b.w. and 500 mg per kg b.w. and the standard drug (Metformin 500 mg/kg b.w.). The levels of blood sugar were measured prior starting therapy (at 0 hours) and 2, 4, and 6 hours after administering the respective treatments [ 23 , 24 ]. 2.5. In vitro antidiabetic assay 2.5.1. Anti Alpha-amylase inhibitory test The inhibitory activity of α-amylase was evaluated utilizing dinitrosalicylic acid [ 25 ]. Briefly, 100 µl of series of concentrations of infusion extract of Salvia verbenaca , Ferula vesceritensis Coss & Dur. and Myrtus communis L (200 to 1200 µg/mL) and acarbose (as a reference) were mixed with 100 µl of (1 U/ml) α-amylase) and 200 µl of sodium phosphate buffer (pH 6.9; 20 mM,). After pre-incubating the samples for 10 min at 25°C, 200 µL of starch solution (1%) prepared in 20 mM sodium phosphate buffer (pH 6.9) was added. For ten minutes, the reaction mixtures were incubated at 25°C. To halt the reactions, 1 mL of dinitrosalicylic acid was added, then for ten minutes, the reaction mixtures were incubated at 25°C. Following the reduction of the reaction mixtures to ambient temperature, a 1:5 dilution with water was executed. Absorbance was subsequently assessed at 540 nm utilizing a CE2041 spectrophotometer (Cecil, Instruments, England). Each experiment was conducted in triplicate. The percentage of the enzyme inhibition was calculated using the following formula: α-amylase inhibition (%) = (Absorbance Control - Absorbance Treatment )/(Absorbance Control ) × 100 2.6. HPLC analysis The infusion extract from three species was analyzed using High-Performance Liquid Chromatography (HPLC) with an Agilent series 1100 system (Agilent Technologies, Palo Alto, CA, USA) equipped with a UV detector and diode array detector (DAD, G1315B). The system was equipped with a quaternary rapid separation pump (G1376A). A Hypersil BDS-C18 column (250 × 4.6 mm, 5µm) served as the stationary phase. A linear gradient of acetic acid (0.2% in water) and acetonitrile over 30 minutes was utilized as the mobile phase, with an injection volume of 10 µL and a flow rate of 1.5 mL/min. Compound identification was based on comparing their retention times to standards. 2.7. Statistical analysis The findings were reported as mean ± standard deviation (SD). In order to compare the samples, a one-way analysis of variance (ANOVA) was employed, followed by Tukey's multiple comparison test. The software Statistica version 6.0 was employed for this analysis. A statistically significant level of P < 0.05 was adopted to define significance. 3. Results and Discussion 3.1. Hypoglycemic study in normal mice The objective of this investigation was to assess the impact of infusion extracts from Salvia verbenaca , Ferula vesceritensis Coss & Dur. and Myrtus communis L (at doses of 100 and 500 mg/kg body weight) on fasting blood sugar reduction at various times (1, 3 and 5 h). The results are presented in Table 1 . The blood glucose level of control group remained unchanged throughout the entire experiment. The oral administration of the standard drug metformin (500 mg/kg b.w) decreased glucose level by 0.15 units after 5h of treatment. It was observed that the changes in mice glycaemia after oral administration of the infusion extracts were a dose-dependent trend for all three plants. The infusion extract of Ferula vesceritensis Coss & Dur. at dose of 500 mg/kg produced a statistically significant (P < 0.05) decrease of 0.20 units in blood glucose levels at all time intervals. This effect was comparable based on the observed reduction values to that of metformin. The infusion extract of Salvia verbenaca reduced the blood glucose levels of mice 5 hours after treatment by 0.09 and 0.12 units for the doses of 100 and 500 mg/kg, respectively, although these reductions were less pronounced compared to Ferula vesceritensis In contrast, Myrtus communis L did not produce statistically significant reductions in glycemia in normal mice at any time during the study, showing decreases of 0.06 and 0.07 units for the respective doses of 100 and 500 mg/kg. These results suggest a relatively stronger glucose-lowering effect of Ferula vesceritensis and a moderate effect of Salvia verbenaca in normoglycemic mice. Table 1 Effects of metformin and infusion extracts on the blood glucose levels of non-diabetic mice. Treatment Dose* Time (h) 0 1 3 5 Control (saline) --- 0.98 ± 0.08 0.97 ± 0.07 0.95 ± 0.06 0.93 ± 0.07 Metformin 500 0.97 ± 0.07 a 0.91 ± 0.06 a 0.86 ± 0.06 a 0.82 ± 0.05 a Salvia verbenaca 100 0.97 ± 0.10 a, b 0.98 ± 0.08 a, b 0.93 ± 0.09 a, b 0.88 ± 0.10 a, b 500 0.98 ± 0.07 a, b 0.95 ± 0.07 a, b 0.91 ± 0.07 a, b 0.86 ± 0.09 a, b Ferula vesceritensis Coss & Dur. 100 0.94 ± 0.07 a, b 0.90 ± 0.07 a, b 0.84 ± 0.04 a, b 0.81 ± 0.07 a, b 500 1.00 ± 0.08 a, b 0.93 ± 0.08 a, b 0.87 ± 0.07 a, b 0.80 ± 0.06 a, b Myrtus communis L 100 0.99 ± 0.06 a, b 0.96 ± 0.06 a, b 0.94 ± 0.07 a, b 0.93 ± 0.06 a, b 500 0.93 ± 0.10 a, b 0.91 ± 0.10 a, b 0.89 ± 0.10 a, b 0.86 ± 0.10 a, b Dose* :(mg/kg b.w.); All values are expressed as mean ± SD, (n = 5); Tukey test: a P < 0.05 compared with control; b P < 0.05 compared with metformin. 3.2. Oral glucose tolerance test The blood glucose levels and reduction percentages of the control, metformin (500 mg/kg b.w.), and the infusion extracts of Salvia verbenaca , Ferula vesceritensis Coss & Dur. and Myrtus communis L. (100 and 500 mg/kg b.w.) at different times intervals (0, 30, 60, 90, and 120 min) are presented in Table 2 . The results shown in Table 2 are also graphically illustrated in Fig. 1 . As illustrated in Table 2 and Fig. 1 , peak blood glucose levels were observed in all groups compared to their baseline concentrations 30 minutes after the oral administration of an high glucose load (4 g/kg), which induced hyperglycemia in mice. After that, metformin (500 mg/kg b.w.) used as the reference medication significantly (P < 0.05) decreased blood glucose levels by 50.69%. The infusion extract of Ferula vesceritensis Coss & Dur., when orally administered at 100 mg/kg b.w., reduced blood glucose levels (P < 0.05), although the percentage reduction was slightly lower than that of the reference drug (49.32%). Interestingly, at a concentration of 500 mg/kg b.w., the infusion extract showed a higher percentage reduction (59.09%) (P < 0.05) in glucose-induced hyperglycemia compared to metformin, representing the highest reduction among all tested groups under the present conditions. At 500 mg/kg b.w., the infusion extract of Salvia verbenaca significantly (P < 0.05) reduced blood glucose levels, achieving a reduction rate comparable to that of the reference drug (50.45%). Conversely, at 100 mg/kg b.w., the percentage decrease in blood glucose was slightly lower (44.74%) than that observed with metformin. Moreover, the infusion extract of Myrtus communis L. at both doses (100 mg/Kg and 500 mg/kg b.w.) did not produce significant changes in blood glucose levels compared to the control group, with reduction percentages of 18.84% and 24.41% for the respective doses. These findings suggest that Ferula vesceritensis may exert a relatively stronger effect in reducing glucose-induced hyperglycemia under the present experimental conditions, while Salvia verbenaca shows a moderate effect. Table 2. The blood sugar levels of mice subjected to a tolerance test for oral glucose compared with metformin and the infusion extracts. Treatment Dose* Blood glucose level (g/L) Time (min) 0 30 60 90 120 Reduction % Control (saline) --- 1.05±0.03 2.08±0.04 1.95±0.04 1.88±0.03 1.79±0.01 13.94 Metformin 500 1.04±0.07 2.15±0.03 1.83±0.05 1.56±0.05 1.06±0.07 50.69 a Salvia verbenaca 100 1.03±0.07 2.19±0.03 1.78±0.04 1.60±0.03 1.21±0.03 44.74 a, b 500 0.98±0.07 2.18±0.04 1.72±0.03 1.43±0.04 1.08±0.06 50.45 a, b Ferula vesceritensis Coss & Dur. 100 1.01±0.06 2.21±0.02 1.87±0.07 1.55±0.04 1.12±0.04 49.32 a, b 500 1.01±0.07 2.20±0.01 1.72±0.03 1.48±0.03 0.90±0.09 59.09 a, b Myrtus communis L 100 1.03±0.06 2.07±0.04 1.90±0.04 1.79±0.04 1.68±0.02 18.84 a, b 500 1.07±0.03 2.13±0.03 1.96±0.01 1.78±0.03 1.62±0.02 23.94 a, b Dose* :(mg/kg b.w); All values are expressed as Mean ± SD, (n = 5); Tukey test: a P <0.05 compared with control; b P < 0.05 compared with Metformin. 3.3. Streptozotocin induced diabetes mice Administering the infusion of each sample orally to diabetic mice induced by streptozotocin at doses of 100 and 500 mg per kg resulted in a significant reduction in blood glucose levels compared with the diabetic control group. This reduction was observed in a dose-dependent trend. Table 3 represents the blood glucose levels in diabetic mice before and after 2, 4, and 6 hours treatments. The infusion extract of Ferula vesceritensis Coss & Dur. at a concentration of 500 mg/kg produced a marked reduction in blood glucose levels at all time points post-treatment, with values reaching 0.80 g/L at 6 h, which was comparable to metformin. Salvia verbenaca infusion extract showed a similar trend to metformin, with final glucose levels of 0.81 g/L at 6 h for the 500 mg/kg dose. In contrast, Myrtus communis L. infusion extract did not produce a marked reduction in blood glucose levels at the administered doses across all time points compared to other treatments. These data suggest that Ferula vesceritensis exhibits a relatively stronger glucose-lowering effect under streptozotocin-induced diabetic conditions, while Salvia verbenaca shows a comparable but slightly less consistent effect. Table 3. The impact of infusion extracts and metformin on blood glucose levels in mice with diabetes induced by streptozotocin. Treatment Dose* Blood glucose level (g/L) Time (hour) 0 2 4 6 Control (saline) --- 2.47± 0.05 2.43±0.05 2.40±0.04 2.36±0.04 Metformin 500 2.56±0.14 a 1.78±0.08 a 1.15±0.04 a 0.88±0.09 a Salvia verbenaca 100 2.57±0.07 a, b 1.72±0.06 a, b 1.2±0.04 a, b 0.94±0.04 a, b 500 2.51±0.08 a, b 1.85±0.08 a, b 1.25±0.07 a, b 0.81±0.05 a, b Ferula vesceritensis Coss & Dur. 100 2.59±0.14 a, b 1.82±0.08 a, b 1.18±0.04 a, b 0.92±0.05 a, b 500 2.53±0.07 a, b 1.47±0.15 a, b 1.23±0.09 a, b 0.80±0.05 a, b Myrtus communis L 100 2.52±0.10 a, b 2.41±0.09 a 2.36±.09 a 2.28±0.06 a 500 2.49±0.09 a, b 2.39±0.05 a, b 2.28±0.01 a, b 2.18±0.02 a, b Dose*: (mg per kg b.w); All values are expressed as Mean ± SD, (n = 5); Tukey test: a P <0.05 compared with control; b P < 0.05 compared with Metformin. 3.4. In vitro antidiabetic assay 3.4.1. Anti alpha-amylase test In the present study, all infusion extracts of Salvia verbenaca , Ferula vesceritensis Coss & Dur. and Myrtus communis L. exhibited a concentration-dependent trend in α-amylase inhibitory activity, as illustrated in Table 4. Ferula vesceritensis Coss & Dur. infusion extract was found to have a significantly higher α-amylase inhibition, ranging from 51.32 to 77.38% at the concentration range of 200–1200 µg/mL. The infusion extract of Salvia verbenaca was able to inhibit the enzyme between 48.05% and 73.26% within the same concentration range. The inhibition achieved by these plants was comparable to that of the reference (acarbose), ranging from 46.10% to 73.05% at the same concentrations. However, the infusion extract of Myrtus communis L exhibited low inhibitory activity against α-amylase, as indicated by our findings. The IC 50 values were derived from graphs plotting α-amylase inhibition against infusion concentrations. The highest inhibitory capacity was observed in Ferula vesceritensis Coss & Dur. infusion extract (IC 50 = 158.40 µg/mL), followed by the infusion extract of Salvia verbenaca (IC 50 = 298.40 µg/mL). Nevertheless, the infusion extract of M yrtus communis L. did not induce significant inhibition of the amylase enzyme (IC 50 = 2101.65 µg/mL). Taken together, these results are in general agreement with the in vivo findings, although direct correlations between in vitro enzyme inhibition and in vivo hypoglycemic effects should be interpreted with caution. Table 4. Amylase inhibitory activity of infusion extracts in comparison with acarbose Extracts α-amylase inhibitory percentage IC 50 µg/mL Concentration μg/mL 200 400 600 800 1000 1200 Acarbose 46,10±0.001 50,43±0.001 55,05±0.001 61,14±0.001 67,09±0.002 73,05±0.001 380.74 Salvia verbenaca 48,05±0.006 52,05±0.001 58,11±0.002 62,01±0.001 67,42±0.001 73,26±0.004 298.40 a Ferula vesceritensis 52,05±0.002 55,41±0.002 61,36±0.004 66,12±0.002 71,21±0.002 77,38±0.003 158.40 a Myrtus communis L 12.55±0.002 16.01±0.004 20.34±0.004 24.02±0.002 29.22±0.001 33.00±0.001 2101.65 b All values are expressed as Mean ± SD, (n = 3); Tukey test: Values with different letters (a, b) were significantly different compared with Acarbose (P <0.05). 3.5. HPLC analysis The infusion extracts were analyzed for the presence of bioactive substances using high-performance liquid chromatography. The chromatograms used to detect phenolic compounds are depicted in Fig. 2 . Table 5 displays the identified phenolic compounds, as illustrated in Fig. 2 . Table 5. Retention times of phenolic compounds identified in infusion extracts of Salvia verbenaca , Ferula vesceritensis Coss & Dur. and Myrtus communis L. Extract Peak Retention Time (min) Compounds Salvia verbenaca 1 1.962 Ascorbic acid 2 5.789 Resorcinol 3 6.176 1.2-dihydroxybenzene 4 7.037 Caffeic acid 5 7.398 Acid di-nito-Salicylic 6 7.817 4-Hydroxybenzaldehyde 7 8.403 Orientin 8 8.551 Rutin 9 9.146 Quercetin-3- O -glycoside 10 9.404 Luteolin 7- O -glucoside 11 9.699 Salicylic acid 12 10.269 Apigenin-7-glucoside 13 10.799 Spiraeoside 14 12.529 3,4,5 trimethoxy trans cinnamic acid 15 13.692 Quercetin 16 14.805 Kaempferol Ferula vesceritensis 1 1.962 Ascorbic acid 2 3.253 Gallic acid 3 4.173 Protocatechuic acid 4 7.719 vanillic acid 5 8.551 Rutin 6 9.118 Ferulic acid 7 10.222 Rosmarinic acid 8 10.963 Sinapic acid 9 13.692 Quercetin 10 14.805 Kaempferol Myrtus communis L 1 3.253 Gallic acid 2 5.376 Ellagic acid 3 7.394 iso vannillic acid 4 9.118 Ferulic acid 5 11.982 p anisic acid 6 12.752 Luteolin 7 13.692 Quercetin 8 17.168 Apigenin The HPLC analysis revealed the presence of various phenolic compounds in Salvia verbenaca , Ferula vesceritensis Coss & Dur. and Myrtus communis L. infusion extracts in polyphenols (Fig. 3 ). Salvia verbenaca infusion contains 16 compounds, 7 of which are phenolic acids and two flavonols: quercetin and kaempferol. The presence of compounds in the heterosidic state includes C-glycoside: Orientin, and five O-glycosides: rutin, spiraeoside, luteolin 7-O-glucoside, Apigenin-7-glucoside, Quercetin-3-b-glycoside. Quercetin and kaempferol are identified as flavonols. The infusion extract of Ferula vesceritensis Coss & Dur. contains 6 phenolic acids and two flavonols: Quercetin and Kaempferol. Rutin is identified as O-glycoside. Ascorbic acid is present as an organic compound in the infusion extracts of both plants. There are five phenolic acids present in Myrtus communis L. infusion extract, along with two flavones (luteolin and apigenin). Quercetin is identified as a flavonol. The development of agents for diabetes management that lack adverse effects remains a challenge within the healthcare system [ 26 ]. In this context, the present research investigated the antidiabetic activity, both in vitro and in vivo , of Salvia verbenaca , Ferula vesceritensis Coss & Dur., and Myrtus communis L., identified in Algerian ethnobotanical studies for their traditional use in diabetes treatment. In all antidiabetic experiments, the infusion extract of the three plants exhibited a general dose-dependent trend in reduction of blood glucose levels. Hypoglycemic tests are used to assess peripheral insulin action [ 27 , 28 ]. It was observed that the infusion extract of Ferula vesceritensis Coss & Dur. showed a stronger glucose-lowering trend across time points compared with metformin and infusion extracts of Salvia verbenaca and Myrtus communis L. The glucose tolerance test is commonly employed to evaluate the body's capacity for glucose metabolism by identifying alterations in post-prandial glucose levels. This test serves as a diagnostic tool for conditions such as diabetes mellitus or insulin resistance [ 29 ]. The infusion extract of Ferula vesceritensis showed a higher reduction in glucose levels, with values comparable to or slightly higher than metformin under the present conditions. The infusion extract of Salvia verbenaca significantly decreased blood glucose levels, achieving a reduction rate similar to that of the reference drug. Similar results were obtained in streptozotocin-induced diabetes assay, regarded as an excellent experimental paradigm for evaluating the effectiveness of hypoglycemic drugs [ 30 ]. Streptozotocin, known for its cytotoxic effects, induces the demise of pancreatic β-cells through DNA alkylation, resulting in fewer active cells and consequently diminishing insulin synthesis and release [ 31 ]. The findings of this work suggest that Ferula vesceritensis may exhibit effects comparable to oral antihyperglycemic agents, leading to a reduction in blood glucose levels in normoglycemic animals [ 32 ]. Salvia verbenaca may act through mechanisms similar to metformin, based on the observed experimental trends [ 33 ]. In contrast, the infusion extract of Myrtus communis L, did not lead to a reduction in blood glucose levels in all in vivo experiments. The integration of in vitro screening methods with in vivo assessments offers a comprehensive approach to evaluating the efficacy of these medicinal plants. The α-amylase inhibitory test revealed that the infusion extract of Ferula vesceritensis exhibited higher inhibitory activity, followed by Salvia verbenaca infusion extract, and this inhibitory effect was comparable to that of acarbose. Unlike the infusion extract of Myrtus communis L., it did not show effectiveness. The results acquired from the in vivo experiments are generally consistent with the observations from the in vitro study, although direct correlations should be interpreted with caution. The main mechanism of action of the hypoglycemic effect of medicinal plants may involve the stimulation of insulin release by β cells or the inhibition of glucose absorption from the intestine or a combination of both [ 5 , 34 ]. Phenolic constituents of plants can be considered as potential agents for diabetes management [ 26 , 35 ]. The phytochemical investigation indicated the presence of rutin and kaempferol in Ferula vesceritensis and Salvia verbenaca infusion extracts, which have been reported to possess antidiabetic-related activities [ 36 , 37 ]. These compounds may contribute to the observed hypoglycemic effects. Apart from these compounds, protocatechuic acid also exhibits antidiabetic-related activity [ 38 , 39 ], and its presence in Ferula vesceritensis may partly explain its relatively stronger activity. Conversely, the phytochemical analysis of Myrtus communis L. suggests a lower abundance of compounds commonly associated with antidiabetic activity, which may explain its limited effect in the present study. 4. Conclusion This study is the first to specifically evaluate the in vitro and in vivo antidiabetic properties of Salvia verbenaca , Ferula vesceritensis Coss & Dur., and Myrtus communis L., which are commonly used in Algerian traditional medicine for diabetes management. Based on the obtained results, it can be suggested that the infusion extracts of Salvia verbenaca and Ferula vesceritensis exhibit significant hypoglycemic activity, which may be associated with their phytochemical composition, particularly rutin, kaempferol, and protocatechuic acid. These findings highlight the potential relevance of these plants as natural sources of bioactive compounds for diabetes management and support their ethnopharmacological use, although further studies are required to confirm their efficacy and safety and to support the development of plant-derived antidiabetic compounds. Declarations Ethical Approval The experimental procedures were approved by the ethical committee of the Algerian Association of Experimental Animal Sciences (88–08/1988) and conducted in adherence to the European Directive 2010/63/EU (EC, 2010) regarding the welfare of animals used for experimental and scientific purposes. Competing interests / COI statement: Not applicable. Funding: This research was funded by the University of Zabol, Zabol, Iran (grant number: IR-UOZ-GR-9186). Authors' contributions: Lilya Harchaoui : Methodology, Conceptualization, Software, Data curation, Writing – review & editing. Saida Ouafi: Visualization, Validation. Wafa Zahnit : Conceptualization, Writing – review & editing. Majid Sharifi-Rad: Writing – review & editing. Mohammed Messaoudi: Writing – review & editing. Acknowledgements: The authors would like to thank the Algerian Ministry of Higher Education and Scientific Research Data availability statement The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. References Della Manna, T., Setian, N., Savoldelli, R. D., et al. (2016). Diabetes mellitus in childhood: An emerging condition in the 21st century. Revista da Associação Médica Brasileira , 62, 594–601. Salehi, B., Ata, A., Kumar, N. V., et al. (2019). Antidiabetic potential of medicinal plants and their active components. Biomolecules , 9, 551. Elujoba, A. A., Odeleye, O., & Ogunyemi, C. (2005). Traditional medicine development for medical and dental primary health care delivery system in Africa. African Journal of Traditional, Complementary and Alternative Medicines , 2, 46–61. Parra-Naranjo, A., Delgado-Montemayor, C., Fraga-López, A., et al. (2017). Acute hypoglycemic and antidiabetic effect of teuhetenone A isolated from Turnera diffusa . Molecules , 22, 599. Zahnit, W., Smara, O., Bechki, L., et al. (2023). In vitro assessment of anti-cholinesterase, anti-lipase, antioxidant activities and photoprotective effect of Algerian Fagonia bruguieri DC extracts. Pharmaceutical Chemistry Journal , 57, 89–100. Ozenda, P. (1958). Flore du Sahara septentrional et central . Paris: Centre National de la Recherche Scientifique. Oughlissi-Dehak, K., Lawton, P., Michalet, S., et al. (2008). Sesquiterpenes from aerial parts of Ferula vesceritensis . Phytochemistry , 69, 1933–1938. Smaili, T., Belkassam, A., Dehimi, K., et al. (2022). Chemical constituents of the essential oil from Algerian pre-Sahara subspecies. Acta Biologica Marisiensis , 5, 34–40. Mrabti, H. N., El Menyiy, N., Charfi, S., et al. (2022). Phytochemistry and biological properties of Salvia verbenaca L.: A comprehensive review. BioMed Research International , 2022. Atzei, A. D. (2003). Le piante nella tradizione popolare della Sardegna . Carlo Delfino Editore. Messaoud, C., Laabidi, A., & Boussaid, M. (2012). Myrtus communis L. infusions: The effect of infusion time on phytochemical composition, antioxidant, and antimicrobial activities. Journal of Food Science , 77, C941–C947. Kemassi, A., Darem, S., Cherif, R., et al. (2014). Recherche et identification de quelques plantes médicinales à caractère hypoglycémiant de la pharmacopée traditionnelle des communautés de la vallée du M’Zab (Sahara septentrional Est Algérien). Journal of Advanced Research in Science , 1, 1–5. Ouelbani, R., Bensari, S., Mouas, T. N., et al. (2016). Ethnobotanical investigations on plants used in folk medicine in the regions of Constantine and Mila (North-East of Algeria). Journal of Ethnopharmacology , 194, 196–218. Khouchlaa, A., Et-Touys, A., Lakhdar, F., et al. (2021). Ethnomedicinal use, phytochemistry, pharmacology, and toxicology of Salvia verbenaca L.: A review. Biointerface Research in Applied Chemistry , 12, 1437–1469. Quézel, P., & Santa, S. (1963). Nouvelle flore de l’Algérie et des régions désertiques méridionales . Kraft, K., & Hobbs, C. (2004). Pocket guide to herbal medicine . Georg Thieme Verlag. Sebai, H., Jabri, M.-A., Souli, A., et al. (2014). Protective effect of Artemisia campestris extract against aspirin-induced gastric lesions and oxidative stress in rats. RSC Advances , 4, 49831–49841. Sah, S. P., Sah, M. L., Juyal, V., et al. (2010). Hypoglycemic activity of aqueous extract of Urtica parviflora Roxb. in normoglycemic rats. International Journal of Phytomedicine , 2. Alene, M., Abdelwuhab, M., Belay, A., et al. (2020). Evaluation of antidiabetic activity of Ajuga integrifolia (Lamiaceae) root extract and solvent fractions in mice. Evidence-Based Complementary and Alternative Medicine , 2020. Belgacem, A., Gdara, N. B., Khemiri, I., et al. (2019). Exploration of hypoglycemic effect of an extract from leaves of a plant from Tunisian pharmacopeia: Artemisia campestris (Asteraceae). African Health Sciences , 19, 2846–2853. Tzeng, T.-F., Liou, S.-S., Chang, C. J., et al. (2014). The ethanol extract of Lonicera japonica (Japanese honeysuckle) attenuates diabetic nephropathy by inhibiting p-38 MAPK activity in streptozotocin-induced diabetic rats. Planta Medica , 80, 121–129. Shewamene, Z., Abdelwuhab, M., & Birhanu, Z. (2015). Methanolic leaf extract of Otostegia integrifolia Benth reduces blood glucose levels in diabetic, glucose loaded and normal rodents. BMC Complementary and Alternative Medicine , 15, 1–7. Belayneh, Y. M., Birhanu, Z., Birru, E. M., et al. (2019). Evaluation of in vivo antidiabetic, antidyslipidemic, and in vitro antioxidant activities of hydromethanolic root extract of Datura stramonium L. (Solanaceae). Journal of Experimental Pharmacology , 29, 29–38. Zeleke, Y. G., Atnafie, S. A., & Aragaw, T. J. (2023). Anti-diabetic activities of hydro-methanolic crude extract and solvent fractions of Heteromorpha arborescens (Apiaceae) leaves in mice. Journal of Experimental Pharmacology , 2023, 107–121. Kwon, Y. I., Apostolidis, E., & Shetty, K. (2008). Inhibitory potential of wine and tea against α-amylase and α-glucosidase for management of hyperglycemia linked to type 2 diabetes. Journal of Food Biochemistry , 32, 15–31. Shewamene, Z., Abdelwuhab, M., & Birhanu, Z. (2015). Methanolic leaf extract of Otostegia integrifolia Benth reduces blood glucose levels in diabetic, glucose loaded and normal rodents. BMC Complementary and Alternative Medicine , 15, 1–7. Hammeso, W. W., Emiru, Y. K., Getahun, K. A., et al. (2019). Antidiabetic and antihyperlipidemic activities of the leaf latex extract of Aloe megalacantha Baker (Aloaceae) in streptozotocin-induced diabetic model. Evidence-Based Complementary and Alternative Medicine , 2019. Tschritter, O., Fritsche, A., Shirkavand, F., et al. (2003). Assessing the shape of the glucose curve during an oral glucose tolerance test. Diabetes Care , 26, 1026–1033. Un, À., & Troubles, A. P. (n.d.). Vitamine A: Utilisations, effets secondaires, interactions, posologies et avertissements. Abu-Abeeleh, M., Bani Ismail, Z. A., Alzaben, K. R., et al. (2010). A preliminary study of the use of human adipose tissue-derived stem cells for the treatment of streptozotocin-induced diabetes mellitus in a rat model. Comparative Clinical Pathology , 19, 1–4. Szkudelski, T. (2001). The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiological Research , 50, 537–546. Davies, M. J., Tringham, J., Troughton, J., et al. (2004). Prevention of type 2 diabetes mellitus: A review of the evidence and its application in a UK setting. Diabetic Medicine , 21, 403–414. Stumvoll, M., Nurjhan, N., Perriello, G., et al. (1995). Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. New England Journal of Medicine , 333, 550–554. Mia, S., Roy, R., Akter, A., et al. (2019). Hypoglycemic effect of leaf extract of Fimbristylis miliacea in mice model. Clinical Phytoscience , 5, 1–3. Tatipamula, V. B., & Kukavica, B. (2021). Phenolic compounds as antidiabetic, anti-inflammatory, and anticancer agents and improvement of their bioavailability by liposomes. Cell Biochemistry and Function , 39, 926–944. Yang, Y., Chen, Z., Zhao, X., et al. (2022). Mechanisms of kaempferol in the treatment of diabetes: A comprehensive and latest review. Frontiers in Endocrinology , 13, 990299. Ghorbani, A. (2017). Mechanisms of antidiabetic effects of flavonoid rutin. Biomedicine & Pharmacotherapy , 96, 305–312. Abdelmageed, M. E., Shehatou, G. S., Suddek, G. M., et al. (2021). Protocatechuic acid improves hepatic insulin resistance and restores vascular oxidative status in type-2 diabetic rats. Environmental Toxicology and Pharmacology , 83, 103577. Harini, R., & Pugalendi, K. V. (2010). Antihyperglycemic effect of protocatechuic acid on streptozotocin-diabetic rats. Journal of Basic and Clinical Physiology and Pharmacology , 21, 79–92. Additional Declarations No competing interests reported. Supplementary Files Graphicalabstract.png Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 28 Apr, 2026 Reviews received at journal 20 Apr, 2026 Reviewers agreed at journal 16 Apr, 2026 Reviewers agreed at journal 14 Apr, 2026 Reviewers agreed at journal 14 Apr, 2026 Reviewers invited by journal 14 Apr, 2026 Editor assigned by journal 14 Apr, 2026 Editor invited by journal 08 Apr, 2026 Submission checks completed at journal 07 Apr, 2026 First submitted to journal 07 Apr, 2026 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-9172706","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":626287575,"identity":"983d472a-c075-48b5-ba11-928d2f8ff8b2","order_by":0,"name":"Lilya Harchaoui","email":"","orcid":"","institution":"University of Sciences and Technology Houari Boumediene","correspondingAuthor":false,"prefix":"","firstName":"Lilya","middleName":"","lastName":"Harchaoui","suffix":""},{"id":626287576,"identity":"8d14809b-f07f-4c29-9bda-77b1771c29ce","order_by":1,"name":"Saida Ouafi","email":"","orcid":"","institution":"University of Sciences and Technology Houari Boumediene","correspondingAuthor":false,"prefix":"","firstName":"Saida","middleName":"","lastName":"Ouafi","suffix":""},{"id":626287579,"identity":"05cb0e47-1cb9-4839-a3f8-1c1bb1291ea0","order_by":2,"name":"Wafa Zahnit","email":"","orcid":"","institution":"University Ferhat Abbas of Setif","correspondingAuthor":false,"prefix":"","firstName":"Wafa","middleName":"","lastName":"Zahnit","suffix":""},{"id":626287580,"identity":"c7a95a1b-261f-43cb-9f0c-3eb45920db40","order_by":3,"name":"Mohammed Messaoudi","email":"","orcid":"","institution":"École Normale Supérieure de Kouba","correspondingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"","lastName":"Messaoudi","suffix":""},{"id":626287581,"identity":"37e62c39-7460-4c1e-873f-83ba94b6bd5a","order_by":4,"name":"Majid Sharifi-Rad","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIie2RsU7DMBCGz7JUFpeuHSL6BEipkNqhoL6KowxZ6M6QwSzNgpiDBO+QR7jopHSJxOqBIVmYMsCCGALCpmJCDh0Z/A033PnT/ScDeDz/E4kCEICzxtaTn7Y4QOGhrWeHKHZqHgMPbYnUX6lOM2yx659my4wzukpXSbHLGnhPIVg65EUtZfmwfZ7fE4eyrpJNUaNkNxWIAB0KSkljRSznEyzViDaFlghjBWLqCLZ4bCSJntY5N1vUJyWhjhT7GFK02SJGFH0r11uSoY6BD27Rjb2F4r1ym8zv6gooqKYDwS7jl66ni3xC/FW9rWbHu6xtu/R87VLMp8jfPQRwCwBHODD0eDwej+ELpRRjmUeR0e4AAAAASUVORK5CYII=","orcid":"","institution":"University of Zabol","correspondingAuthor":true,"prefix":"","firstName":"Majid","middleName":"","lastName":"Sharifi-Rad","suffix":""}],"badges":[],"createdAt":"2026-03-19 20:08:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9172706/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9172706/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107554543,"identity":"f0b5cd99-1fff-47de-b4e5-1e74f6dbcc44","added_by":"auto","created_at":"2026-04-22 14:47:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":66540,"visible":true,"origin":"","legend":"\u003cp\u003eOral glucose tolerance test (OGTT) in mice\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9172706/v1/4189c75fab70f33c66edb059.png"},{"id":107554545,"identity":"0e6302c3-eb00-4256-9d3a-c66c98acee3b","added_by":"auto","created_at":"2026-04-22 14:47:38","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":108973,"visible":true,"origin":"","legend":"\u003cp\u003eHPLC chromatograms of infusion extracts obtained at 300 nm (\u003cstrong\u003eA\u003c/strong\u003e):\u003cem\u003e Ferula vesceritensis\u003c/em\u003e; (\u003cstrong\u003eB\u003c/strong\u003e):\u003cem\u003e Salvia verbenaca;\u003c/em\u003e (\u003cstrong\u003eC\u003c/strong\u003e):\u003cem\u003eMyrtus communis\u003c/em\u003e L.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9172706/v1/34b3b2768995c20d478897bc.png"},{"id":107554544,"identity":"cfd2068d-78c9-4440-9792-6a7878259d39","added_by":"auto","created_at":"2026-04-22 14:47:38","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":30494,"visible":true,"origin":"","legend":"\u003cp\u003eMain phenolic compounds identified in infusion extracts of \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. and \u003cem\u003eMyrtus communis\u003c/em\u003e L.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9172706/v1/51bb4bd688b8b88a352baaf5.png"},{"id":107706341,"identity":"1bb7eec1-3076-493e-8322-edd1f195ffb3","added_by":"auto","created_at":"2026-04-24 09:17:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":747552,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9172706/v1/1e332f41-296d-4698-b035-ef6e79400709.pdf"},{"id":107554542,"identity":"1eeff1a2-d868-46f1-abe3-a9888910f325","added_by":"auto","created_at":"2026-04-22 14:47:38","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":181837,"visible":true,"origin":"","legend":"","description":"","filename":"Graphicalabstract.png","url":"https://assets-eu.researchsquare.com/files/rs-9172706/v1/61c6d1e1faee413d53986f45.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"Phytochemical Profiling and Antidiabetic Activity of Algerian Medicinal Plants: In Vitro α-Amylase Inhibition and In Vivo Glucose-Lowering Effects","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eDiabetes mellitus, characterized by chronic hyperglycemia, is a global health concern with an increasing prevalence across various populations [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Its impact on individuals, such as reduced treatment effectiveness and increased adverse effects and the burden it places on healthcare systems have spurred extensive research into novel approaches for its prevention and management. There is growing interest in exploring alternative, complementary, and natural sources for effective antidiabetic treatments [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The search for new and more sustainable treatments has led to the investigation of medicinal plants as sources of bioactive compounds with therapeutic potential. Globally, medicinal plants have served as an essential therapeutic resource, with over half of the global population relying on these plants, using extracts or active components as a traditional medicine to meet their fundamental healthcare needs [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. These plants have shown potential in reducing blood glucose levels and mitigating the complications associated with diabetes [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These plants have been traditionally used by local healers, and understanding their use through ethnopharmacological approaches is crucial to validate indigenous medical practices. Algeria possesses an important reservoir of medicinal plants owing to its rich biodiversity. In the southern regions of the nation, indigenous communities continue to depend on traditional healers for addressing various health concerns such as diabetes [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Among the medicinal plants used in Algerian herbal medicine for the treatment of diabetes are \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. and \u003cem\u003eMyrtus communis\u003c/em\u003e L.\u003c/p\u003e \u003cp\u003e \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. is among the six species belonging to the \u003cem\u003eFerula\u003c/em\u003e genus in Algeria; this specie is abundant in south east of the country [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The aerial part of this plant is used in traditional medicine to treat headaches, fever, and throat infections [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In Algeria Sahara, the genus \u003cem\u003eSalvia\u003c/em\u003e is represented by three species, including \u003cem\u003eSalvia verbenaca\u003c/em\u003e subsp. clandestina (L.) Batt. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Various traditional applications of this plant have been documented, such as reducing fever, easing digestive and spasmodic pain, and addressing liver disorders [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. \u003cem\u003eMyrtus communis\u003c/em\u003e L known as true myrtle, is a medicinal plant native to the Mediterranean area and belongs to the Myrtaceae family [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. According to traditional medicine data, myrtle has been widely used for the treatment of various ailments, including pulmonary diseases, and viral and bacterial infections [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Ethnobotanical investigation indicates that these plants are widely used for reducing blood sugar levels [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, to date, no scientific studies have comprehensively evaluated the bioactive compounds and their \u003cem\u003ein vitro\u003c/em\u003e and \u003cem\u003ein vivo\u003c/em\u003e antidiabetic activities. To our knowledge, this is the first comprehensive study integrating phytochemical profiling with \u003cem\u003ein vitro\u003c/em\u003e and \u003cem\u003ein vivo\u003c/em\u003e biological evaluation for these three medicinal plants used in Algerian traditional medicine. The aim of this study was to evaluate antidiabetic activities of \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. and \u003cem\u003eMyrtus communis\u003c/em\u003e L through \u003cem\u003ein vivo\u003c/em\u003e and \u003cem\u003ein vitro\u003c/em\u003e essays to verify the validity of their traditional use. Furthermore, a chromatographic phytochemical analysis was conducted to identify bioactive compounds potentially responsible for their antidiabetic activity.\u003c/p\u003e"},{"header":"2. Experimental","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Plant Material\u003c/h2\u003e \u003cp\u003eThe aerial parts of \u003cem\u003eSalvia verbenaca\u003c/em\u003e and \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. were collected from El atteuf in Ghardaia region 32\u0026deg; 28\u0026prime; 60\u0026Prime; north, 3\u0026deg; 40\u0026prime; 60\u0026Prime; east (northern Algerian Sahara). \u003cem\u003eMyrtus communis\u003c/em\u003e L. aerial parts were gathered from Cherchell station 36\u0026deg; 36\u0026prime; 27\u0026Prime; north, 2\u0026deg; 11\u0026prime; 26\u0026Prime; east, a coastal town west of Algiers.\u003c/p\u003e \u003cp\u003eThe plants were identification by botanist, Prof. Saida Ouafi, according to Quezel and Santa [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Standard voucher specimens were conserved at the herbarium of Chemistry Department, University of Mentouri- Algeria (\u003cem\u003eSalvia verbenaca\u003c/em\u003e : Sv15/137, \u003cem\u003eFerula vesceritensis\u003c/em\u003e : Fv03/10 and \u003cem\u003eMyrtus communis\u003c/em\u003e: Mc32/61). The harvested plant aerial parts were air-dried until completely dehydrated at room temperature. Subsequently, the desiccated samples were finely powdered using an electric blender and stored in paper bags until their use.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Animals\u003c/h2\u003e \u003cp\u003eAdult male albino mice, \u003cem\u003eMus musculus\u003c/em\u003e, weighing 20\u0026ndash;25 g, were procured from the Pasteur Institute of Algeria. The animals were kept in a standard laboratory environment at a temperature of 24\u0026thinsp;\u0026plusmn;\u0026thinsp;2˚C and a 12-hour light/dark cycle, with access to food and water provided \u003cem\u003ead libitum.\u003c/em\u003e The experimental procedures were approved by the ethical committee of the Algerian Association of Experimental Animal Sciences (88\u0026ndash;08/1988) and conducted in adherence to the European Directive 2010/63/EU (EC, 2010) regarding the welfare of animals used for experimental and scientific purposes. The use of albino mice in the investigation of \u003cem\u003ein vivo\u003c/em\u003e antidiabetic activity of plants infusion extracts was approved by the Ethical Committee of Animal Experimentation (CEEA) of University of Sciences and Technology Houari Boumediene (USTHB) with approved Ref N\u0026deg;: CEEA-USTHB-08-2023/11118, Algeria.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Plant extraction\u003c/h2\u003e \u003cp\u003eThe infusion extract of each plant sample was prepared using a traditional technique according to the method of Kraft and Hobbs [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], involving the addition of boiling distilled water/saline solution to the sample (1 g per 50 mL). After allowing it to steep at room temperature for 10 minutes, the mixture was filtered using Whatman grade No. 1 filter paper. Thereafter, the infusion extract underwent lyophilization and was reconstituted in methanol for chromatographic analysis [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. \u003cem\u003eIn vivo\u003c/em\u003e antidiabetic assays\u003c/h2\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.4.1. Grouping and dosing of animals\u003c/h2\u003e \u003cp\u003eIn the context of Streptozotocin-induced diabetes and hypoglycemic and oral glucose tests, mice were randomized into eight groups of five mice each. As a negative control, Group I was administered a solution containing 10 mL per kg b.w. of distilled water. Metformin was administered to Group II (the positive control) at 500 mg per kg b.w. \u003cem\u003eSalvia verbenaca\u003c/em\u003e infusion extract was administered at 100 and 500 mg per kg b.w. to Groups III and IV, respectively. Similarly, the subjects in groups V and VI were administered infusion extract of \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. at respective concentrations of 100 and 500 mg/kg body weight. In conclusion, infusion extract of \u003cem\u003eMyrtus communis L.\u003c/em\u003e was administered to Groups VII and VIII at concentrations of 500 mg per kg b.w. and 100 mg per kg b.w., respectively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.4.2. Measurement of blood glucose level\u003c/h2\u003e \u003cp\u003eBlood samples used for the blood glucose analysis were collected from the tail tip of each animal for all assessments. A blood glucometer (Accu Check Active, Roche, Germany) was employed to ascertain the blood glucose levels.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003e2.4.3. Hypoglycemic study in normal mice\u003c/h2\u003e \u003cp\u003eThe hypoglycemic effect of infusion extracts from three species was investigated in non-diabetic mice. The animals underwent a 16-hour overnight fasting period before the commencement of the experiment. A glucometer determined the initial fasting blood sugar levels the subsequent morning at 0 h. Subsequently, the animals in their respective groups were orally administered distilled water, the infusion extracts of \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur., \u003cem\u003eMyrtus communis\u003c/em\u003e L. (100 and 500 mg per kg b.w.) and the reference drug (Metformin 500 mg per kg b.w.). Blood glucose levels were subsequently measured at 1 hour, 3 hours, and 5 hours following the administration of the experimental medications in order to evaluate their hypoglycemic impact [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e2.4.4. Oral glucose tolerance test\u003c/h2\u003e \u003cp\u003eOral glucose tolerance assay of infusion extracts of three plants was conducted in normal mice. After a 16-hour overnight fasting period, mice within their respective groups were orally administered various treatments: distilled water, infusion extracts of \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur., \u003cem\u003eMyrtus communis\u003c/em\u003e L. (100 and 500 mg per kg b.w.), and the reference drug (Metformin 500 mg per kg b.w.). Thirty minutes following this administration, the animals were orally administered a 40% glucose solution (4 g/kg). Blood glucose levels were measured prior to the treatments (representing baseline fasting glucose levels) and at 30 min, 60 min, 90 min, and 120 min after the injection of glucose [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The percentage decrease in the level of blood glucose following 120 minutes was calculated using the following:\u003c/p\u003e \u003cp\u003e \u003cb\u003e% = ((Bgl\u003c/b\u003e \u003csub\u003e\u003cb\u003e30 min\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e- Blgl\u003c/b\u003e \u003csub\u003e\u003cb\u003e120 min\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e) / Bgl\u003c/b\u003e \u003csub\u003e\u003cb\u003e30 min\u003c/b\u003e\u003c/sub\u003e\u003cb\u003e) \u0026times; 100\u003c/b\u003e [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eBgl \u003csub\u003e30 min\u003c/sub\u003e\u003c/strong\u003e \u003cp\u003eBlood glucose level after 30 min of glucose ingestion\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eBlgl\u003c/b\u003e \u003csub\u003e\u003cb\u003e120 min\u003c/b\u003e\u003c/sub\u003e: Blood glucose level at t :120 min\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section3\"\u003e \u003ch2\u003e2.4.5. Streptozotocin induced diabetes mice\u003c/h2\u003e \u003cp\u003eAfter an overnight fasting period for the animals, blood glucose levels were measured before inducing diabetes. Diabetes was induced experimentally by administering freshly prepared streptozotocin (STZ) through intraperitoneal injection (45 mg per kg in 0.1 M sodium citrate buffer, pH 4.5) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Thirty minutes after the injection, mice were given unrestricted delivery of food and water. Animals' diabetes confirmation was based on elevated blood glucose levels observed after 72 hours post-injection; only mice with fasting blood glucose levels exceeding 2 g/L were included in the study [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Following this, mice in their designated groups received different oral treatments: buffer solution, infusion extracts of \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur., \u003cem\u003eMyrtus communis\u003c/em\u003e L. at 1000 mg per kg b.w. and 500 mg per kg b.w. and the standard drug (Metformin 500 mg/kg b.w.). The levels of blood sugar were measured prior starting therapy (at 0 hours) and 2, 4, and 6 hours after administering the respective treatments [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e2.5. \u003cem\u003eIn vitro\u003c/em\u003e antidiabetic assay\u003c/h2\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003ch2\u003e2.5.1. Anti Alpha-amylase inhibitory test\u003c/h2\u003e \u003cp\u003eThe inhibitory activity of α-amylase was evaluated utilizing dinitrosalicylic acid [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Briefly, 100 \u0026micro;l of series of concentrations of infusion extract of \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. and \u003cem\u003eMyrtus communis\u003c/em\u003e L (200 to 1200 \u0026micro;g/mL) and acarbose (as a reference) were mixed with 100 \u0026micro;l of (1 U/ml) α-amylase) and 200 \u0026micro;l of sodium phosphate buffer (pH 6.9; 20 mM,). After pre-incubating the samples for 10 min at 25\u0026deg;C, 200 \u0026micro;L of starch solution (1%) prepared in 20 mM sodium phosphate buffer (pH 6.9) was added. For ten minutes, the reaction mixtures were incubated at 25\u0026deg;C. To halt the reactions, 1 mL of dinitrosalicylic acid was added, then for ten minutes, the reaction mixtures were incubated at 25\u0026deg;C. Following the reduction of the reaction mixtures to ambient temperature, a 1:5 dilution with water was executed. Absorbance was subsequently assessed at 540 nm utilizing a CE2041 spectrophotometer (Cecil, Instruments, England). Each experiment was conducted in triplicate. The percentage of the enzyme inhibition was calculated using the following formula:\u003c/p\u003e \u003cp\u003eα-amylase inhibition (%) = (Absorbance\u003csub\u003eControl\u003c/sub\u003e - Absorbance\u003csub\u003eTreatment\u003c/sub\u003e)/(Absorbance\u003csub\u003eControl\u003c/sub\u003e) \u0026times; 100\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e2.6. HPLC analysis\u003c/h2\u003e \u003cp\u003eThe infusion extract from three species was analyzed using High-Performance Liquid Chromatography (HPLC) with an Agilent series 1100 system (Agilent Technologies, Palo Alto, CA, USA) equipped with a UV detector and diode array detector (DAD, G1315B). The system was equipped with a quaternary rapid separation pump (G1376A). A Hypersil BDS-C18 column (250 \u0026times; 4.6 mm, 5\u0026micro;m) served as the stationary phase. A linear gradient of acetic acid (0.2% in water) and acetonitrile over 30 minutes was utilized as the mobile phase, with an injection volume of 10 \u0026micro;L and a flow rate of 1.5 mL/min. Compound identification was based on comparing their retention times to standards.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e2.7. Statistical analysis\u003c/h2\u003e \u003cp\u003eThe findings were reported as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). In order to compare the samples, a one-way analysis of variance (ANOVA) was employed, followed by Tukey's multiple comparison test. The software Statistica version 6.0 was employed for this analysis. A statistically significant level of P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was adopted to define significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results and Discussion","content":"\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1. Hypoglycemic study in normal mice\u003c/h2\u003e\n \u003cp\u003eThe objective of this investigation was to assess the impact of infusion extracts from \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. and \u003cem\u003eMyrtus communis\u003c/em\u003e L (at doses of 100 and 500 mg/kg body weight) on fasting blood sugar reduction at various times (1, 3 and 5 h). The results are presented in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The blood glucose level of control group remained unchanged throughout the entire experiment. The oral administration of the standard drug metformin (500 mg/kg b.w) decreased glucose level by 0.15 units after 5h of treatment. It was observed that the changes in mice glycaemia after oral administration of the infusion extracts were a dose-dependent trend for all three plants. The infusion extract of \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. at dose of 500 mg/kg produced a statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) decrease of 0.20 units in blood glucose levels at all time intervals. This effect was comparable based on the observed reduction values to that of metformin. The infusion extract of \u003cem\u003eSalvia verbenaca\u003c/em\u003e reduced the blood glucose levels of mice 5 hours after treatment by 0.09 and 0.12 units for the doses of 100 and 500 mg/kg, respectively, although these reductions were less pronounced compared to \u003cem\u003eFerula vesceritensis\u003c/em\u003e In contrast, \u003cem\u003eMyrtus communis\u003c/em\u003e L did not produce statistically significant reductions in glycemia in normal mice at any time during the study, showing decreases of 0.06 and 0.07 units for the respective doses of 100 and 500 mg/kg.\u003c/p\u003e\n \u003cp\u003eThese results suggest a relatively stronger glucose-lowering effect of \u003cem\u003eFerula vesceritensis\u003c/em\u003e and a moderate effect of \u003cem\u003eSalvia verbenaca\u003c/em\u003ein normoglycemic mice.\u0026nbsp;\u003c/p\u003e\n \u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eEffects of metformin and infusion extracts on the blood glucose levels of non-diabetic mice.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\n \u003cp\u003eDose*\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e\n \u003cp\u003eTime (h)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eControl (saline)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e0.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e0.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eMetformin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e0.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e0.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e0.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eSalvia verbenaca\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e0.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e0.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e0.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e0.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e0.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e0.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e0.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e0.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e0.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e0.80\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eMyrtus communis\u003c/em\u003e L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e0.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e0.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e0.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e0.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e0.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 \u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eDose* :(mg/kg b.w.); All values are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, (n\u0026thinsp;=\u0026thinsp;5); Tukey test: \u003csup\u003ea\u003c/sup\u003eP \u0026lt;\u0026thinsp;0.05 compared with control; \u003csup\u003eb\u003c/sup\u003eP \u0026lt; 0.05 compared with metformin.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2. Oral glucose tolerance test\u003c/h2\u003e\n \u003cp\u003eThe blood glucose levels and reduction percentages of the control, metformin (500 mg/kg b.w.), and the infusion extracts of \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. and \u003cem\u003eMyrtus communis\u003c/em\u003e L. (100 and 500 mg/kg b.w.) at different times intervals (0, 30, 60, 90, and 120 min) are presented in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The results shown in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e are also graphically illustrated in Fig. \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n \u003cp\u003eAs illustrated in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig. \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, peak blood glucose levels were observed in all groups compared to their baseline concentrations 30 minutes after the oral administration of an high glucose load (4 g/kg), which induced hyperglycemia in mice. After that, metformin (500 mg/kg b.w.) used as the reference medication significantly (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) decreased blood glucose levels by 50.69%.\u003c/p\u003e\n \u003cp\u003eThe infusion extract of \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur., when orally administered at 100 mg/kg b.w., reduced blood glucose levels (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), although the percentage reduction was slightly lower than that of the reference drug (49.32%). Interestingly, at a concentration of 500 mg/kg b.w., the infusion extract showed a higher percentage reduction (59.09%) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in glucose-induced hyperglycemia compared to metformin, representing the highest reduction among all tested groups under the present conditions. At 500 mg/kg b.w., the infusion extract of \u003cem\u003eSalvia verbenaca\u003c/em\u003e significantly (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) reduced blood glucose levels, achieving a reduction rate comparable to that of the reference drug (50.45%). Conversely, at 100 mg/kg b.w., the percentage decrease in blood glucose was slightly lower (44.74%) than that observed with metformin. Moreover, the infusion extract of \u003cem\u003eMyrtus communis\u003c/em\u003e L. at both doses (100 mg/Kg and 500 mg/kg b.w.) did not produce significant changes in blood glucose levels compared to the control group, with reduction percentages of 18.84% and 24.41% for the respective doses.\u003c/p\u003e\n \u003cp\u003eThese findings suggest that \u003cem\u003eFerula vesceritensis\u003c/em\u003e may exert a relatively stronger effect in reducing glucose-induced hyperglycemia under the present experimental conditions, while \u003cem\u003eSalvia verbenaca\u003c/em\u003e shows a moderate effect.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eThe blood sugar levels of mice subjected to a tolerance test for oral glucose compared with metformin and the infusion extracts.\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDose*\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" style=\"width: 449px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood glucose level (g/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 449px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime (min)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e30\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e60\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e90\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e120\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eReduction\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl (saline)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.05\u0026plusmn;0.03\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e2.08\u0026plusmn;0.04\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.95\u0026plusmn;0.04\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.88\u0026plusmn;0.03\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.79\u0026plusmn;0.01\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e13.94\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMetformin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.04\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e2.15\u0026plusmn;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.83\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.56\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.06\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e50.69\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSalvia verbenaca\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.03\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e2.19\u0026plusmn;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.78\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.60\u0026plusmn;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.21\u0026plusmn;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e44.74\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e0.98\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e2.18\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.72\u0026plusmn;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.43\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.08\u0026plusmn;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e50.45\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eFerula vesceritensis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCoss \u0026amp; Dur.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.01\u0026plusmn;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e2.21\u0026plusmn;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.87\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.55\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.12\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e49.32\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.01\u0026plusmn;0.07\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e2.20\u0026plusmn;0.01\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.72\u0026plusmn;0.03\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.48\u0026plusmn;0.03\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e0.90\u0026plusmn;0.09\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e59.09\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eMyrtus communis L\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.03\u0026plusmn;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e2.07\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.90\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.79\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.68\u0026plusmn;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e18.84\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.07\u0026plusmn;0.03\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e2.13\u0026plusmn;0.03\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.96\u0026plusmn;0.01\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.78\u0026plusmn;0.03\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.62\u0026plusmn;0.02\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e23.94\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eDose* :(mg/kg b.w); All values are expressed as Mean \u0026plusmn; SD, (n = 5); Tukey test: \u003csup\u003ea\u003c/sup\u003eP \u0026lt;0.05 compared with control; \u003csup\u003eb\u003c/sup\u003eP \u0026lt; 0.05 compared with Metformin.\u003c/p\u003e\n \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3. Streptozotocin induced diabetes mice\u003c/h2\u003e\n \u003cp\u003eAdministering the infusion of each sample orally to diabetic mice induced by streptozotocin at doses of 100 and 500 mg per kg resulted in a significant reduction in blood glucose levels compared with the diabetic control group. This reduction was observed in a dose-dependent trend. Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e represents the blood glucose levels in diabetic mice before and after 2, 4, and 6 hours treatments.\u003c/p\u003e\n \u003cp\u003eThe infusion extract of \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. at a concentration of 500 mg/kg produced a marked reduction in blood glucose levels at all time points post-treatment, with values reaching 0.80 g/L at 6 h, which was comparable to metformin. \u003cem\u003eSalvia verbenaca\u003c/em\u003e infusion extract showed a similar trend to metformin, with final glucose levels of 0.81 g/L at 6 h for the 500 mg/kg dose. In contrast, \u003cem\u003eMyrtus communis\u003c/em\u003e L. infusion extract did not produce a marked reduction in blood glucose levels at the administered doses across all time points compared to other treatments. These data suggest that \u003cem\u003eFerula vesceritensis\u003c/em\u003e exhibits a relatively stronger glucose-lowering effect under streptozotocin-induced diabetic conditions, while \u003cem\u003eSalvia verbenaca\u003c/em\u003e shows a comparable but slightly less consistent effect.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eThe impact of infusion extracts and metformin on blood glucose levels in mice with diabetes induced by streptozotocin.\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"603\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDose*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 376px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood glucose level (g/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 376px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime (hour)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl (saline)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e2.47\u0026plusmn; 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e2.43\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e2.40\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e2.36\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMetformin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 93px;\"\u003e\n \u003cp\u003e2.56\u0026plusmn;0.14\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e1.78\u0026plusmn;0.08\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.15\u0026plusmn;0.04\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.88\u0026plusmn;0.09\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" rowspan=\"2\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSalvia verbenaca\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e2.57\u0026plusmn;0.07\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e1.72\u0026plusmn;0.06\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.2\u0026plusmn;0.04\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.94\u0026plusmn;0.04\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e2.51\u0026plusmn;0.08\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e1.85\u0026plusmn;0.08\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.25\u0026plusmn;0.07\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.81\u0026plusmn;0.05\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" rowspan=\"2\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eFerula vesceritensis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCoss \u0026amp; Dur.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 93px;\"\u003e\n \u003cp\u003e2.59\u0026plusmn;0.14\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e1.82\u0026plusmn;0.08\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.18\u0026plusmn;0.04\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.92\u0026plusmn;0.05\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e2.53\u0026plusmn;0.07\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e1.47\u0026plusmn;0.15\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e1.23\u0026plusmn;0.09\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.80\u0026plusmn;0.05\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" rowspan=\"2\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eMyrtus communis\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;L\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e2.52\u0026plusmn;0.10\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e2.41\u0026plusmn;0.09\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e2.36\u0026plusmn;.09\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e2.28\u0026plusmn;0.06\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 93px;\"\u003e\n \u003cp\u003e2.49\u0026plusmn;0.09\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 96px;\"\u003e\n \u003cp\u003e2.39\u0026plusmn;0.05\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 95px;\"\u003e\n \u003cp\u003e2.28\u0026plusmn;0.01\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 93px;\"\u003e\n \u003cp\u003e2.18\u0026plusmn;0.02\u003csup\u003e\u0026nbsp;a, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eDose*: (mg per kg b.w); All values are expressed as Mean \u0026plusmn; SD, (n = 5); Tukey test: \u003csup\u003ea\u003c/sup\u003eP \u0026lt;0.05 compared with control; \u003csup\u003eb\u003c/sup\u003eP \u0026lt; 0.05 compared with Metformin.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\n \u003ch2\u003e3.4. \u003cem\u003eIn vitro\u003c/em\u003e antidiabetic assay\u003c/h2\u003e\n \u003cdiv id=\"Sec21\" class=\"Section3\"\u003e\n \u003ch2\u003e3.4.1. Anti alpha-amylase test\u003c/h2\u003e\n \u003cp\u003eIn the present study, all infusion extracts of \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. and \u003cem\u003eMyrtus communis\u003c/em\u003e L. exhibited a concentration-dependent trend in \u0026alpha;-amylase inhibitory activity, as illustrated in Table 4. \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. infusion extract was found to have a significantly higher \u0026alpha;-amylase inhibition, ranging from 51.32 to 77.38% at the concentration range of 200\u0026ndash;1200 \u0026micro;g/mL. The infusion extract of \u003cem\u003eSalvia verbenaca\u003c/em\u003e was able to inhibit the enzyme between 48.05% and 73.26% within the same concentration range. The inhibition achieved by these plants was comparable to that of the reference (acarbose), ranging from 46.10% to 73.05% at the same concentrations. However, the infusion extract of \u003cem\u003eMyrtus communis\u003c/em\u003e L exhibited low inhibitory activity against \u0026alpha;-amylase, as indicated by our findings. The IC\u003csub\u003e50\u003c/sub\u003e values were derived from graphs plotting \u0026alpha;-amylase inhibition against infusion concentrations. The highest inhibitory capacity was observed in \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. infusion extract (IC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;158.40 \u0026micro;g/mL), followed by the infusion extract of \u003cem\u003eSalvia verbenaca\u003c/em\u003e (IC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;298.40 \u0026micro;g/mL). Nevertheless, the infusion extract of M\u003cem\u003eyrtus communis\u003c/em\u003e L. did not induce significant inhibition of the amylase enzyme (IC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;2101.65 \u0026micro;g/mL). Taken together, these results are in general agreement with the in vivo findings, although direct correlations between in vitro enzyme inhibition and in vivo hypoglycemic effects should be interpreted with caution.\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 4.\u0026nbsp;\u003c/strong\u003eAmylase inhibitory activity of infusion extracts in comparison with acarbose\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"699\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExtracts\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" style=\"width: 510px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026alpha;-amylase inhibitory percentage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIC\u003csub\u003e50\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026micro;g/mL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConcentration\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026mu;g/mL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e1200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAcarbose\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e46,10\u0026plusmn;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e50,43\u0026plusmn;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e55,05\u0026plusmn;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e61,14\u0026plusmn;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e67,09\u0026plusmn;0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e73,05\u0026plusmn;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e380.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSalvia verbenaca\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e48,05\u0026plusmn;0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e52,05\u0026plusmn;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e58,11\u0026plusmn;0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e62,01\u0026plusmn;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e67,42\u0026plusmn;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e73,26\u0026plusmn;0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e298.40\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eFerula vesceritensis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e52,05\u0026plusmn;0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e55,41\u0026plusmn;0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e61,36\u0026plusmn;0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e66,12\u0026plusmn;0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e71,21\u0026plusmn;0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e77,38\u0026plusmn;0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e158.40\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eMyrtus communis\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e12.55\u0026plusmn;0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e16.01\u0026plusmn;0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e20.34\u0026plusmn;0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e24.02\u0026plusmn;0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e29.22\u0026plusmn;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e33.00\u0026plusmn;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e2101.65\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eAll values are expressed as Mean \u0026plusmn; SD, (n = 3); Tukey test: Values with different letters (a, b) were significantly different compared with Acarbose (P \u0026lt;0.05).\u003c/p\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\n \u003ch2\u003e3.5. HPLC analysis\u003c/h2\u003e\n \u003cp\u003eThe infusion extracts were analyzed for the presence of bioactive substances using high-performance liquid chromatography. The chromatograms used to detect phenolic compounds are depicted in Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n \u003cp\u003eTable \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e5\u003c/span\u003e displays the identified phenolic compounds, as illustrated in Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 5.\u0026nbsp;\u003c/strong\u003eRetention times of phenolic compounds identified in infusion extracts of\u0026nbsp;\u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. and \u003cem\u003eMyrtus communis\u003c/em\u003e L.\u003c/p\u003e\n \u003ctable float=\"No\" id=\"Tabc\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eExtract\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003ePeak\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eRetention Time (min)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eCompounds\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\" morerows=\"15\" rowspan=\"16\"\u003e\n \u003cp\u003e\u003cem\u003eSalvia verbenaca\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e1.962\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eAscorbic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e5.789\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eResorcinol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e6.176\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e1.2-dihydroxybenzene\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e7.037\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eCaffeic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e7.398\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eAcid di-nito-Salicylic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e7.817\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e4-Hydroxybenzaldehyde\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e8.403\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eOrientin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e8.551\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eRutin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e9.146\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eQuercetin-3-\u003cem\u003eO\u003c/em\u003e-glycoside\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e9.404\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eLuteolin 7-\u003cem\u003eO\u003c/em\u003e-glucoside\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e9.699\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eSalicylic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e10.269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eApigenin-7-glucoside\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e10.799\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eSpiraeoside\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e12.529\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e3,4,5 trimethoxy trans cinnamic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e13.692\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eQuercetin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e14.805\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKaempferol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\" morerows=\"9\" rowspan=\"10\"\u003e\n \u003cp\u003e\u003cem\u003eFerula vesceritensis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e1.962\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eAscorbic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e3.253\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eGallic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e4.173\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eProtocatechuic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e7.719\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003evanillic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e8.551\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eRutin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e9.118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eFerulic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e10.222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eRosmarinic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e10.963\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eSinapic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e13.692\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eQuercetin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e14.805\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eKaempferol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e\n \u003cp\u003e\u003cem\u003eMyrtus communis\u003c/em\u003e L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e3.253\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eGallic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e5.376\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eEllagic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e7.394\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eiso vannillic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e9.118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eFerulic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e11.982\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003ep anisic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e12.752\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eLuteolin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e13.692\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eQuercetin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e17.168\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eApigenin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe HPLC analysis revealed the presence of various phenolic compounds in \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. and \u003cem\u003eMyrtus communis\u003c/em\u003e L. infusion extracts in polyphenols (Fig. \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). \u003cem\u003eSalvia verbenaca\u003c/em\u003e infusion contains 16 compounds, 7 of which are phenolic acids and two flavonols: quercetin and kaempferol. The presence of compounds in the heterosidic state includes C-glycoside: Orientin, and five O-glycosides: rutin, spiraeoside, luteolin 7-O-glucoside, Apigenin-7-glucoside, Quercetin-3-b-glycoside. Quercetin and kaempferol are identified as flavonols. The infusion extract of \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. contains 6 phenolic acids and two flavonols: Quercetin and Kaempferol. Rutin is identified as O-glycoside. Ascorbic acid is present as an organic compound in the infusion extracts of both plants. There are five phenolic acids present in \u003cem\u003eMyrtus communis\u003c/em\u003e L. infusion extract, along with two flavones (luteolin and apigenin). Quercetin is identified as a flavonol.\u003c/p\u003e\n\u003cp\u003eThe development of agents for diabetes management that lack adverse effects remains a challenge within the healthcare system [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eIn this context, the present research investigated the antidiabetic activity, both \u003cem\u003ein vitro\u003c/em\u003e and \u003cem\u003ein vivo\u003c/em\u003e, of \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur., and \u003cem\u003eMyrtus communis\u003c/em\u003e L., identified in Algerian ethnobotanical studies for their traditional use in diabetes treatment. In all antidiabetic experiments, the infusion extract of the three plants exhibited a general dose-dependent trend in reduction of blood glucose levels. Hypoglycemic tests are used to assess peripheral insulin action [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. It was observed that the infusion extract of \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur. showed a stronger glucose-lowering trend across time points compared with metformin and infusion extracts of \u003cem\u003eSalvia verbenaca\u003c/em\u003e and \u003cem\u003eMyrtus communis\u003c/em\u003e L. The glucose tolerance test is commonly employed to evaluate the body\u0026apos;s capacity for glucose metabolism by identifying alterations in post-prandial glucose levels. This test serves as a diagnostic tool for conditions such as diabetes mellitus or insulin resistance [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The infusion extract of \u003cem\u003eFerula vesceritensis\u003c/em\u003e showed a higher reduction in glucose levels, with values comparable to or slightly higher than metformin under the present conditions. The infusion extract of \u003cem\u003eSalvia verbenaca\u003c/em\u003e significantly decreased blood glucose levels, achieving a reduction rate similar to that of the reference drug. Similar results were obtained in streptozotocin-induced diabetes assay, regarded as an excellent experimental paradigm for evaluating the effectiveness of hypoglycemic drugs [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Streptozotocin, known for its cytotoxic effects, induces the demise of pancreatic \u0026beta;-cells through DNA alkylation, resulting in fewer active cells and consequently diminishing insulin synthesis and release [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The findings of this work suggest that \u003cem\u003eFerula vesceritensis\u003c/em\u003e may exhibit effects comparable to oral antihyperglycemic agents, leading to a reduction in blood glucose levels in normoglycemic animals [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. \u003cem\u003eSalvia verbenaca\u003c/em\u003e may act through mechanisms similar to metformin, based on the observed experimental trends [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In contrast, the infusion extract of \u003cem\u003eMyrtus communis\u003c/em\u003e L, did not lead to a reduction in blood glucose levels in all in \u003cem\u003evivo\u003c/em\u003e experiments. The integration of \u003cem\u003ein vitro\u003c/em\u003e screening methods with \u003cem\u003ein vivo\u003c/em\u003e assessments offers a comprehensive approach to evaluating the efficacy of these medicinal plants. The \u0026alpha;-amylase inhibitory test revealed that the infusion extract of \u003cem\u003eFerula vesceritensis\u003c/em\u003e exhibited higher inhibitory activity, followed by \u003cem\u003eSalvia verbenaca\u003c/em\u003e infusion extract, and this inhibitory effect was comparable to that of acarbose. Unlike the infusion extract of \u003cem\u003eMyrtus communis\u003c/em\u003e L., it did not show effectiveness. The results acquired from the in vivo experiments are generally consistent with the observations from the in vitro study, although direct correlations should be interpreted with caution. The main mechanism of action of the hypoglycemic effect of medicinal plants may involve the stimulation of insulin release by \u0026beta; cells or the inhibition of glucose absorption from the intestine or a combination of both [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Phenolic constituents of plants can be considered as potential agents for diabetes management [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. The phytochemical investigation indicated the presence of rutin and kaempferol in \u003cem\u003eFerula vesceritensis\u003c/em\u003e and \u003cem\u003eSalvia verbenaca\u003c/em\u003e infusion extracts, which have been reported to possess antidiabetic-related activities [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. These compounds may contribute to the observed hypoglycemic effects. Apart from these compounds, protocatechuic acid also exhibits antidiabetic-related activity [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e], and its presence in \u003cem\u003eFerula vesceritensis\u003c/em\u003e may partly explain its relatively stronger activity. Conversely, the phytochemical analysis of \u003cem\u003eMyrtus communis\u003c/em\u003e L. suggests a lower abundance of compounds commonly associated with antidiabetic activity, which may explain its limited effect in the present study.\u003c/p\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eThis study is the first to specifically evaluate the in vitro and in vivo antidiabetic properties of \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur., and \u003cem\u003eMyrtus communis\u003c/em\u003e L., which are commonly used in Algerian traditional medicine for diabetes management. Based on the obtained results, it can be suggested that the infusion extracts of \u003cem\u003eSalvia verbenaca\u003c/em\u003e and \u003cem\u003eFerula vesceritensis\u003c/em\u003e exhibit significant hypoglycemic activity, which may be associated with their phytochemical composition, particularly rutin, kaempferol, and protocatechuic acid. These findings highlight the potential relevance of these plants as natural sources of bioactive compounds for diabetes management and support their ethnopharmacological use, although further studies are required to confirm their efficacy and safety and to support the development of plant-derived antidiabetic compounds.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e The experimental procedures were approved by the ethical committee of the Algerian Association of Experimental Animal Sciences (88\u0026ndash;08/1988) and conducted in adherence to the European Directive 2010/63/EU (EC, 2010) regarding the welfare of animals used for experimental and scientific purposes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests / COI statement:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis research was funded by the University of Zabol, Zabol, Iran (grant number: IR-UOZ-GR-9186).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLilya Harchaoui\u003c/strong\u003e: Methodology, Conceptualization, Software, Data curation, Writing \u0026ndash; review \u0026amp; editing. \u003cstrong\u003eSaida Ouafi:\u003c/strong\u003e Visualization, Validation. \u003cstrong\u003eWafa Zahnit\u003c/strong\u003e: Conceptualization, Writing \u0026ndash; review \u0026amp; editing. \u003cstrong\u003eMajid Sharifi-Rad:\u0026nbsp;\u003c/strong\u003eWriting \u0026ndash; review \u0026amp; editing.\u0026nbsp;\u003cstrong\u003eMohammed Messaoudi:\u0026nbsp;\u003c/strong\u003eWriting \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eThe authors would like to thank the Algerian Ministry of Higher Education and Scientific Research\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDella Manna, T., Setian, N., Savoldelli, R. D., et al. (2016). Diabetes mellitus in childhood: An emerging condition in the 21st century. \u003cem\u003eRevista da Associa\u0026ccedil;\u0026atilde;o M\u0026eacute;dica Brasileira\u003c/em\u003e, 62, 594\u0026ndash;601.\u003c/li\u003e\n\u003cli\u003eSalehi, B., Ata, A., Kumar, N. V., et al. (2019). Antidiabetic potential of medicinal plants and their active components. \u003cem\u003eBiomolecules\u003c/em\u003e, 9, 551.\u003c/li\u003e\n\u003cli\u003eElujoba, A. A., Odeleye, O., \u0026amp; Ogunyemi, C. (2005). Traditional medicine development for medical and dental primary health care delivery system in Africa. \u003cem\u003eAfrican Journal of Traditional, Complementary and Alternative Medicines\u003c/em\u003e, 2, 46\u0026ndash;61.\u003c/li\u003e\n\u003cli\u003eParra-Naranjo, A., Delgado-Montemayor, C., Fraga-L\u0026oacute;pez, A., et al. (2017). Acute hypoglycemic and antidiabetic effect of teuhetenone A isolated from \u003cem\u003eTurnera diffusa\u003c/em\u003e. \u003cem\u003eMolecules\u003c/em\u003e, 22, 599.\u003c/li\u003e\n\u003cli\u003eZahnit, W., Smara, O., Bechki, L., et al. (2023). In vitro assessment of anti-cholinesterase, anti-lipase, antioxidant activities and photoprotective effect of Algerian \u003cem\u003eFagonia bruguieri\u003c/em\u003e DC extracts. \u003cem\u003ePharmaceutical Chemistry Journal\u003c/em\u003e, 57, 89\u0026ndash;100.\u003c/li\u003e\n\u003cli\u003eOzenda, P. (1958). \u003cem\u003eFlore du Sahara septentrional et central\u003c/em\u003e. Paris: Centre National de la Recherche Scientifique.\u003c/li\u003e\n\u003cli\u003eOughlissi-Dehak, K., Lawton, P., Michalet, S., et al. (2008). Sesquiterpenes from aerial parts of \u003cem\u003eFerula vesceritensis\u003c/em\u003e. \u003cem\u003ePhytochemistry\u003c/em\u003e, 69, 1933\u0026ndash;1938.\u003c/li\u003e\n\u003cli\u003eSmaili, T., Belkassam, A., Dehimi, K., et al. (2022). Chemical constituents of the essential oil from Algerian pre-Sahara subspecies. \u003cem\u003eActa Biologica Marisiensis\u003c/em\u003e, 5, 34\u0026ndash;40.\u003c/li\u003e\n\u003cli\u003eMrabti, H. N., El Menyiy, N., Charfi, S., et al. (2022). Phytochemistry and biological properties of \u003cem\u003eSalvia verbenaca\u003c/em\u003e L.: A comprehensive review. \u003cem\u003eBioMed Research International\u003c/em\u003e, 2022.\u003c/li\u003e\n\u003cli\u003eAtzei, A. D. (2003). \u003cem\u003eLe piante nella tradizione popolare della Sardegna\u003c/em\u003e. Carlo Delfino Editore.\u003c/li\u003e\n\u003cli\u003eMessaoud, C., Laabidi, A., \u0026amp; Boussaid, M. (2012). \u003cem\u003eMyrtus communis\u003c/em\u003e L. infusions: The effect of infusion time on phytochemical composition, antioxidant, and antimicrobial activities. \u003cem\u003eJournal of Food Science\u003c/em\u003e, 77, C941\u0026ndash;C947.\u003c/li\u003e\n\u003cli\u003eKemassi, A., Darem, S., Cherif, R., et al. (2014). Recherche et identification de quelques plantes m\u0026eacute;dicinales \u0026agrave; caract\u0026egrave;re hypoglyc\u0026eacute;miant de la pharmacop\u0026eacute;e traditionnelle des communaut\u0026eacute;s de la vall\u0026eacute;e du M\u0026rsquo;Zab (Sahara septentrional Est Alg\u0026eacute;rien). \u003cem\u003eJournal of Advanced Research in Science\u003c/em\u003e, 1, 1\u0026ndash;5.\u003c/li\u003e\n\u003cli\u003eOuelbani, R., Bensari, S., Mouas, T. N., et al. (2016). Ethnobotanical investigations on plants used in folk medicine in the regions of Constantine and Mila (North-East of Algeria). \u003cem\u003eJournal of Ethnopharmacology\u003c/em\u003e, 194, 196\u0026ndash;218.\u003c/li\u003e\n\u003cli\u003eKhouchlaa, A., Et-Touys, A., Lakhdar, F., et al. (2021). Ethnomedicinal use, phytochemistry, pharmacology, and toxicology of \u003cem\u003eSalvia verbenaca\u003c/em\u003e L.: A review. \u003cem\u003eBiointerface Research in Applied Chemistry\u003c/em\u003e, 12, 1437\u0026ndash;1469.\u003c/li\u003e\n\u003cli\u003eQu\u0026eacute;zel, P., \u0026amp; Santa, S. (1963). \u003cem\u003eNouvelle flore de l\u0026rsquo;Alg\u0026eacute;rie et des r\u0026eacute;gions d\u0026eacute;sertiques m\u0026eacute;ridionales\u003c/em\u003e.\u003c/li\u003e\n\u003cli\u003eKraft, K., \u0026amp; Hobbs, C. (2004). \u003cem\u003ePocket guide to herbal medicine\u003c/em\u003e. Georg Thieme Verlag.\u003c/li\u003e\n\u003cli\u003eSebai, H., Jabri, M.-A., Souli, A., et al. (2014). Protective effect of \u003cem\u003eArtemisia campestris\u003c/em\u003e extract against aspirin-induced gastric lesions and oxidative stress in rats. \u003cem\u003eRSC Advances\u003c/em\u003e, 4, 49831\u0026ndash;49841.\u003c/li\u003e\n\u003cli\u003eSah, S. P., Sah, M. L., Juyal, V., et al. (2010). Hypoglycemic activity of aqueous extract of \u003cem\u003eUrtica parviflora\u003c/em\u003e Roxb. in normoglycemic rats. \u003cem\u003eInternational Journal of Phytomedicine\u003c/em\u003e, 2.\u003c/li\u003e\n\u003cli\u003eAlene, M., Abdelwuhab, M., Belay, A., et al. (2020). Evaluation of antidiabetic activity of \u003cem\u003eAjuga integrifolia\u003c/em\u003e (Lamiaceae) root extract and solvent fractions in mice. \u003cem\u003eEvidence-Based Complementary and Alternative Medicine\u003c/em\u003e, 2020.\u003c/li\u003e\n\u003cli\u003eBelgacem, A., Gdara, N. B., Khemiri, I., et al. (2019). Exploration of hypoglycemic effect of an extract from leaves of a plant from Tunisian pharmacopeia: \u003cem\u003eArtemisia campestris\u003c/em\u003e (Asteraceae). \u003cem\u003eAfrican Health Sciences\u003c/em\u003e, 19, 2846\u0026ndash;2853.\u003c/li\u003e\n\u003cli\u003eTzeng, T.-F., Liou, S.-S., Chang, C. J., et al. (2014). The ethanol extract of \u003cem\u003eLonicera japonica\u003c/em\u003e (Japanese honeysuckle) attenuates diabetic nephropathy by inhibiting p-38 MAPK activity in streptozotocin-induced diabetic rats. \u003cem\u003ePlanta Medica\u003c/em\u003e, 80, 121\u0026ndash;129.\u003c/li\u003e\n\u003cli\u003eShewamene, Z., Abdelwuhab, M., \u0026amp; Birhanu, Z. (2015). Methanolic leaf extract of \u003cem\u003eOtostegia integrifolia\u003c/em\u003e Benth reduces blood glucose levels in diabetic, glucose loaded and normal rodents. \u003cem\u003eBMC Complementary and Alternative Medicine\u003c/em\u003e, 15, 1\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eBelayneh, Y. M., Birhanu, Z., Birru, E. M., et al. (2019). Evaluation of in vivo antidiabetic, antidyslipidemic, and in vitro antioxidant activities of hydromethanolic root extract of \u003cem\u003eDatura stramonium\u003c/em\u003e L. (Solanaceae). \u003cem\u003eJournal of Experimental Pharmacology\u003c/em\u003e, 29, 29\u0026ndash;38.\u003c/li\u003e\n\u003cli\u003eZeleke, Y. G., Atnafie, S. A., \u0026amp; Aragaw, T. J. (2023). Anti-diabetic activities of hydro-methanolic crude extract and solvent fractions of \u003cem\u003eHeteromorpha arborescens\u003c/em\u003e (Apiaceae) leaves in mice. \u003cem\u003eJournal of Experimental Pharmacology\u003c/em\u003e, 2023, 107\u0026ndash;121.\u003c/li\u003e\n\u003cli\u003eKwon, Y. I., Apostolidis, E., \u0026amp; Shetty, K. (2008). Inhibitory potential of wine and tea against \u0026alpha;-amylase and \u0026alpha;-glucosidase for management of hyperglycemia linked to type 2 diabetes. \u003cem\u003eJournal of Food Biochemistry\u003c/em\u003e, 32, 15\u0026ndash;31.\u003c/li\u003e\n\u003cli\u003eShewamene, Z., Abdelwuhab, M., \u0026amp; Birhanu, Z. (2015). Methanolic leaf extract of \u003cem\u003eOtostegia integrifolia\u003c/em\u003e Benth reduces blood glucose levels in diabetic, glucose loaded and normal rodents. \u003cem\u003eBMC Complementary and Alternative Medicine\u003c/em\u003e, 15, 1\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eHammeso, W. W., Emiru, Y. K., Getahun, K. A., et al. (2019). Antidiabetic and antihyperlipidemic activities of the leaf latex extract of \u003cem\u003eAloe megalacantha\u003c/em\u003e Baker (Aloaceae) in streptozotocin-induced diabetic model. \u003cem\u003eEvidence-Based Complementary and Alternative Medicine\u003c/em\u003e, 2019.\u003c/li\u003e\n\u003cli\u003eTschritter, O., Fritsche, A., Shirkavand, F., et al. (2003). Assessing the shape of the glucose curve during an oral glucose tolerance test. \u003cem\u003eDiabetes Care\u003c/em\u003e, 26, 1026\u0026ndash;1033.\u003c/li\u003e\n\u003cli\u003eUn, \u0026Agrave;., \u0026amp; Troubles, A. P. (n.d.). Vitamine A: Utilisations, effets secondaires, interactions, posologies et avertissements.\u003c/li\u003e\n\u003cli\u003eAbu-Abeeleh, M., Bani Ismail, Z. A., Alzaben, K. R., et al. (2010). A preliminary study of the use of human adipose tissue-derived stem cells for the treatment of streptozotocin-induced diabetes mellitus in a rat model. \u003cem\u003eComparative Clinical Pathology\u003c/em\u003e, 19, 1\u0026ndash;4.\u003c/li\u003e\n\u003cli\u003eSzkudelski, T. (2001). The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. \u003cem\u003ePhysiological Research\u003c/em\u003e, 50, 537\u0026ndash;546.\u003c/li\u003e\n\u003cli\u003eDavies, M. J., Tringham, J., Troughton, J., et al. (2004). Prevention of type 2 diabetes mellitus: A review of the evidence and its application in a UK setting. \u003cem\u003eDiabetic Medicine\u003c/em\u003e, 21, 403\u0026ndash;414.\u003c/li\u003e\n\u003cli\u003eStumvoll, M., Nurjhan, N., Perriello, G., et al. (1995). Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. \u003cem\u003eNew England Journal of Medicine\u003c/em\u003e, 333, 550\u0026ndash;554.\u003c/li\u003e\n\u003cli\u003eMia, S., Roy, R., Akter, A., et al. (2019). Hypoglycemic effect of leaf extract of \u003cem\u003eFimbristylis miliacea\u003c/em\u003e in mice model. \u003cem\u003eClinical Phytoscience\u003c/em\u003e, 5, 1\u0026ndash;3.\u003c/li\u003e\n\u003cli\u003eTatipamula, V. B., \u0026amp; Kukavica, B. (2021). Phenolic compounds as antidiabetic, anti-inflammatory, and anticancer agents and improvement of their bioavailability by liposomes. \u003cem\u003eCell Biochemistry and Function\u003c/em\u003e, 39, 926\u0026ndash;944.\u003c/li\u003e\n\u003cli\u003eYang, Y., Chen, Z., Zhao, X., et al. (2022). Mechanisms of kaempferol in the treatment of diabetes: A comprehensive and latest review. \u003cem\u003eFrontiers in Endocrinology\u003c/em\u003e, 13, 990299.\u003c/li\u003e\n\u003cli\u003eGhorbani, A. (2017). Mechanisms of antidiabetic effects of flavonoid rutin. \u003cem\u003eBiomedicine \u0026amp; Pharmacotherapy\u003c/em\u003e, 96, 305\u0026ndash;312.\u003c/li\u003e\n\u003cli\u003eAbdelmageed, M. E., Shehatou, G. S., Suddek, G. M., et al. (2021). Protocatechuic acid improves hepatic insulin resistance and restores vascular oxidative status in type-2 diabetic rats. \u003cem\u003eEnvironmental Toxicology and Pharmacology\u003c/em\u003e, 83, 103577.\u003c/li\u003e\n\u003cli\u003eHarini, R., \u0026amp; Pugalendi, K. V. (2010). Antihyperglycemic effect of protocatechuic acid on streptozotocin-diabetic rats. \u003cem\u003eJournal of Basic and Clinical Physiology and Pharmacology\u003c/em\u003e, 21, 79\u0026ndash;92.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Diabetes, medicinal plants, streptozotocin, antidiabetic activity, α-amylase","lastPublishedDoi":"10.21203/rs.3.rs-9172706/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9172706/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eVarious phytotherapeutic compounds with hypoglycemic properties offer a promising avenue to combat diabetes and its associated complications. This study was carried out to investigate the in vivo and in vitro antidiabetic activity and bioactive compounds of \u003cem\u003eSalvia verbenaca\u003c/em\u003e, \u003cem\u003eFerula vesceritensis\u003c/em\u003e Coss \u0026amp; Dur., and \u003cem\u003eMyrtus communis\u003c/em\u003e L., which are used in Algerian traditional medicine. The in vivo antidiabetic assays of infusion extracts of the three plants at 100 and 500 mg/kg b.w, were performed using a hypoglycemic study in normal mice, an oral glucose tolerance test, and streptozotocin-induced diabetic mice. The α-amylase inhibitory test was used to determine the in vitro antidiabetic activity. Phytochemical composition and bioactive profiling were determined using HPLC analysis. The findings indicated a general agreement between in vivo and in vitro antidiabetic effects, rather than a direct quantitative correlation. In the in vivo antidiabetic activities, the infusion extract of \u003cem\u003eF. vesceritensis\u003c/em\u003e displayed significantly (P\u0026lt;0.05) higher potency in reducing glycemia, glucose load–induced hyperglycemia, and in alleviating streptozotocin-induced diabetes, highlighting its potential as a source of bioactive compounds for therapeutic applications, with effects comparable to or higher than metformin under the tested conditions. \u003cem\u003eS. verbenaca\u003c/em\u003e infusion extract showed a comparable blood glucose reduction to the reference drug. Similar findings were obtained in the α-amylase inhibitory test, where the infusion extract of \u003cem\u003eF. vesceritensis\u003c/em\u003e showed strong inhibitory activity, while \u003cem\u003eS. verbenaca\u003c/em\u003e also exhibited comparable inhibitory effects relative to the reference under the tested conditions. The phytochemical analysis revealed the presence of rutin and kaempferol in \u003cem\u003eF. vesceritensis\u003c/em\u003e and \u003cem\u003eS. verbenaca\u003c/em\u003einfusion extracts, and their absence in \u003cem\u003eM. communis\u003c/em\u003e infusion extract, which may explain their observed bioactivity and supports their relevance as natural products with antidiabetic potential. However, further in vivo and clinical studies are required to confirm these findings and their translational relevance.\u003c/p\u003e","manuscriptTitle":"Phytochemical Profiling and Antidiabetic Activity of Algerian Medicinal Plants: In Vitro α-Amylase Inhibition and In Vivo Glucose-Lowering Effects","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-22 14:47:29","doi":"10.21203/rs.3.rs-9172706/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-28T14:21:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-20T12:04:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"162045715614688530649077638853800040686","date":"2026-04-16T07:59:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"66060832087528194468742274401818420383","date":"2026-04-14T16:18:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"151464604075926969230611874040862242886","date":"2026-04-14T06:01:08+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-14T05:59:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-14T05:35:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-08T10:41:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-07T19:35:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-04-07T15:58:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a89e81d4-c74a-42a9-8710-feba8844bb6b","owner":[],"postedDate":"April 22nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":66654025,"name":"Biological sciences/Biochemistry"},{"id":66654026,"name":"Biological sciences/Drug discovery"},{"id":66654027,"name":"Health sciences/Medical research"},{"id":66654028,"name":"Biological sciences/Plant sciences"}],"tags":[],"updatedAt":"2026-04-22T14:47:29+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-22 14:47:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9172706","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9172706","identity":"rs-9172706","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: preprint-html

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2026) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00