Sechium edule var. nigrum spinosum consumption has a hypoglycemic and antioxidant effect in older people diabetic

Sechium edule var. nigrum spinosum consumption has a hypoglycemic and antioxidant effect in older people diabetic | 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 Sechium edule var. nigrum spinosum consumption has a hypoglycemic and antioxidant effect in older people diabetic Juana Rosado-Pérez, Laura Daniela Barroso-Pérez, Graciela Gavia-García, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6935192/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Chronic hyperglycemia, characteristic of type 2 diabetes mellitus (DM2), promotes oxidative stress (OxS). Therefore, it is necessary to strengthen the antioxidant defenses of diabetic patients, especially the elderly. Sechium edule contains high amounts of bioactives, which possess hypoglycemic and antioxidant properties, so we aimed to determine its effects in older diabetic patients. A quasi-experimental study was carried out in 33 older diabetic adults: (i) placebo group (PG; n = 14); (ii) experimental group (EG; n = 19). Glycosylated hemoglobin (HbA1c), lipoperoxides (LPO), protein carbonylation (PC), Total Oxidant Status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), superoxide dismutase, glutathione peroxidase, and catalase enzyme activity were measured pre and post-intervention. In the EG, a statistically significant decrease in HbA1c was observed (EG baseline 8.9 ± 2.2 post 7.8 ± 2.0), as well as in LPO, PC, TOS and OSI (LPO baseline 0.243 ± 0.067, post 0.222 ± 0.050; PC baseline 29.4 ± 10, post 19.2 ± 6; TOS baseline 6.0 ± 2.6, post 3.1 ± 1.8; OSI baseline 5.7 ± 3.1 post 2.0 ± 1.1); coupled with a significative increase in TAS (baseline 0.94 ± 0.29 post 1.22 ± 0.28), modifications not observed in the PG. The results suggest Sechium edule has hypoglycemic and antioxidant effects. Health sciences/Endocrinology Health sciences/Health care Health sciences/Medical research Sechium edule hypoglycemic antioxidant elderly type 2 diabetes Figures Figure 1 Figure 2 Figure 3 Introduction Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic hyperglycemia secondary to defects in the action and production of insulin with alterations in the intermediate metabolism of lipids and proteins. Chronic hyperglycemia favors the development of oxidative stress (OxS), a biochemical alteration that occurs when the production of reactive species exceeds the antioxidant response capacity and oxidative damage to biomolecules occurs with modifications at the cellular, tissue, and systemic levels; this process is linked to pathophysiology of micro and macroangiopathies, typical complications of this disease [1,3]. Likewise, OxS has been pointed out as a condition present in aging, so older people with DM2 have greater OxS and susceptibility to damage [4]. Given the high prevalence of this disease and the debilitating nature of its complications, it is considered a global health problem due to the high direct and indirect costs associated with its treatment [5]. In México, the prevalence is 18.3% in the adult population and increases to 37% among the population over 60; therefore, finding strategies that contribute to its treatment is a current issue [6]. In this sense, considering that a high percentage of older adults consume alternative natural treatments and based on the background (clinical and preclinical) that the bioactive compounds pre-sent in the Sechium edule fruit (flavonoids, phenolic acids, and cucurbitacins) have an antioxidant and hypoglycemic effect [7-9]. In this regard, our research group has consistently demonstrated that the consumption of Sechium edule (1.5g daily) in capsules has a hypoglycemic, antioxidant and anti-inflammatory effect in older adults with metabolic syndrome (MetS), in whom the reversal of the same has been observed because of the impact on the regulation of lipids, glucose and blood pressure. Likewise, in addition to the increase in the activity of antioxidant enzymes, the increased expression of their RNA and the erythroid factor Nrf2, regulator of the antioxidant response, was observed [10-12]. These findings suggest that capsules have great potential for use in patients with T2DM, in whom any of these effects would be beneficial and would favor control. For this reason, the purpose of this study is to explore the effect of consuming the dry extract of Sechium edule in older adults with T2DM. Methods Experimental design The study population was recruited through an open call distributed by printed invitations (leaflets) and digitally (social networks) specifying the objectives of the study and the inclusion criteria, which were to be over 60 years of age, clinically diagnosed with T2DM, preferably without comorbidities, without renal damage nor glycemic unevenness (HbA1c < 11%) and under treatment with oral hypoglycemic agents, without antioxidant intake and without exercising in the three months before the intervention. The Research Bioethics and Biosafety Committee of the Faculty of Higher Studies Zaragoza approved the study UNAM (FESZ-CE/22-118-22). Intervention A population of n = 60 adults over 60 years was recruited, of which 17 did not meet the inclusion criteria. A sample of n = 43 older adults was studied. After signing the in-formed consent, they were randomly assigned to two groups: (i) experimental (EG) n = 22, who consumed 1.5g of Sechium edule per day (three capsules of 500 mg) for three months, and (ii) placebo (PG) n = 21 who consumed three placebo capsules of equal appearance, also for three months. A group was created via social media to maintain ongoing contact with participants and promote adherence. Participants were also scheduled to receive monthly appointments to deliver the treatment and receive feedback. Regarding pharmacological treatment, they were instructed to continue their physician-prescribed treatment, diet, and regular physical activity during the intervention. Follow-up was conducted with monthly medical visits. All participants continued their oral hypoglycemic agent (metformin); none were prescribed insulin. Through the intervention, three individuals from the EG and seven from the PG dropped out of the intervention because of logistical questions, (change of address, medical appointments elsewhere on the same day as the sample collection, lack of a companion to attend appointments) so finally, the data from n = 19 in the EG and n = 14 in the GP were analyzed. Figure 1 shows the study participants' flow (Fig. 1 ). The pharmaceutical design of the capsules was carried out at the Faculty of Higher Studies Zaragoza, the fruits of Sechium edule were donated by the Interdisciplinary Research Group on S. edule in Mexico A.C. (GISeM), and the primary treatment (to produce the powder of Sechium edule ) was carried out at Faculty of Higher Studies Zaragoza, using food grade equipment. Subsequently, manufacturing and packaging on a larger scale was carried out by a certified pharmaceutical company expert in nutraceuticals, which delivered the product in bottles containing 90 capsules, which is sufficient treatment for 30 days. The placebo capsules looked the same as those of Sechium edule but contained talc and lactose monohydrate (pharmaceutical grade) in accordance with the United States Pharmacopeia (USP) (Sigma, St. Louis, MO, USA, EE.UU.). Phytochemical analysis of Sechium edule capsules revealed that they contained the following amounts of the bioactive compounds 0.71 µg cucurbitacin I, 6.11 µg cucurbitacin D, 89.9 µg cucurbitacin B and 154.8 µg of cucurbitacin E; about flavonoids, 0.014 µg of apigenin, 1.30 µg of quercetin, 2.38 µg of myricetin, 14.2 µg of phlorizin, 45.5 µg of rutin and 48.8 µg of naringenin; regarding phenolic acids contains 38.8 µg of gallic acid, 9.3 µg of caffeic, 8.7 µg of syringic acid, 7.0 µg of ferulic acid, 3.3 µg of protocatechuic, 1.4 µg of acid chlorogenic, 1.7 µg of p-coumaric acid and 0.11µg of p-hydroxybenzoic acid [ 11 ]. Biochemical analysis Samples After an 8-hour fast, the blood samples were taken by venipuncture into vacutainer/siliconized tubes without anticoagulant to get serum for the determinations of glucose, renal profile, and lipid profile; with ethylenediamine tetra acetic acid (EDTA) for the measurement of hemoglobin A1c (HbA1c) and heparinized tubes for OxS testing. 500 µL of whole heparinized blood was separated for superoxide dismutase (SOD), 75 µL for gluthatione peroxidase (GPx), 100 µL for catalase (CAT), 100 µL of heparinized plasma for total antioxidant status (TAS), 100 µL of heparinized plasma for total oxidant status (TOS), 100 µL of heparinized plasma for protein carbonylation (PC) and 500 µL for lipid peroxidation (LPO). SOD, CAT, TAS, TOS and GPx techniques were performed in 96-well plates, which were measured on a Multiskan Go reader (Thermo Scientific, Denver, CO, USA). Blood chemistry was performed using colorimetric techniques (Randox Laboratories Ltd., Antrim UK) on a Selectra Junior analyzer (Vital Scientific, Dieren, The Netherlands); glycosylated hemoglobin (HbA1c) was determined by an immunoturbidimetry technique (Spinreact, Spain) in the same analyzer. The coefficients of variation for all determinations (intra-assay and inter-assay) were less than 5%. The measurements were taken from all participants before and after three months of treatment. Plasma Thiobarbituric Acid Reactive Substances (TBARS) In this determination, the reaction between thiobarbituric acid (TBA) (0.11 mol/L) (Sigma, St. Louis, MO, USA) and malondialdehyde (MDA) in acid conditions (phosphoric acid, H3PO4, 0.2 mol/L) (Sigma, St. Louis, MO, USA) produces a pink pigment (the adduct TBA-MDA) which absorbs at 535 nm. In this assay, the addition of butylated hydroxytoluene (BHT) (Sigma, St. Louis, MO, USA) (12.6 mM) prevents the amplification of the peroxidation. In this assay, 200µL of plasma, 25 µL of BHT, 200µL of H3PO4, and 25 µL of TBA were incubated at 90°C for 45 min. The mix was cooled in ice to end the reaction, then 500 µL of butanol (Sigma, St. Louis, MO, USA) and 50 µL of a saturated solution of sodium chloride (NaCl) (Sigma, St. Louis, MO, USA) were added. The product must be read at 535 and 572 nm to correct baseline absorption. A calibration curve was used for the quantification [ 13 ]. Proteins Carbonylation 2,4-dinitrophenylhydrazine (DNPH) (Sigma, St. Louis, MO, USA) test was carried out to quantify carbonylated proteins. For this technique, 20µL of heparinized plasma and 20 µL of DNPH (10 mM in 0.5 M H3PO4) were incubated for 10 min at room temperature with agitation, and 20 µL of 6 M sodium hydroxide (NaOH) was added. After 10 more minutes of incubation in the same conditions, absorbance was measured at 450 nm against a blank sample. Protein concentration was determined using a 1.41 mg/mL standard of bovine serum albumin (BSA) and commercial Bradford reagent (Bio-Rad, Hercules, CA, USA). Whole Blood Superoxide Dismutase In this method, the xanthine and xanthine oxidase reactions produce superoxide radicals, which react with 2-(4-iodophenyl)-3-(4-nitrophenol)-5-phenyl-tetrazolium chloride and form the dye red formazan, which is read at 505 nm. The enzyme present in the sample inhibits this reaction. SOD activity was determined with a commercial kit (Randox Laboratories Ltd., Antrim, UK). Whole blood Glutathione Peroxidase Glutathione oxidation by cumene hydroperoxide is catalyzed by glutathione peroxidase in the presence of glutathione reductase and reduced nicotinamide adenine dinucleotide phosphate (NADPH). Oxidized glutathione is converted into the reduced form with the simultaneous oxidation of NADPH to NADP+. The absorbance decrease is measured at 340 nm (Randox Laboratories Ltd., Antrim, UK). The SOD/GPx ratio was calculated. Catalase Activity The activity of the CAT enzyme was measured with a hydrogen peroxide (H 2 O 2 ) inhibition assay using H 2 O 2 (Sigma, St. Louis, MO, USA) as a substrate. This was a spectrophotometric technique. 10 µl of heparinized total blood was incorporated into 190µL of working solution (0.1 M phosphate buffer and 20 mM H 2 O 2 ). Absorbance detection was performed at 240 nm, inspecting the waste away from the H 2 O 2 concentration every 15 s for 2 min [ 14 ]. Plasma Total Antioxidant Status (TAS) This assay is founded on the generation of the ABTS + cation radical, from the reaction of 2,20-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) with metmyoglobin and H 2 O 2 . The bluish-green coloration of this radical is inhibited by the antioxidants in the sample and is read at 600 nm (Randox Laboratories Ltd., Antrim, UK). The antioxidant gap (AOGAP) was calculated too. The following equation is used: AOGAP = (TAS mmol- [(albumin (mmol) * 0.69) + uric acid (mmol)] [ 15 ]. Total oxidant status (TOS) The commercial kit (Rel Assay Diagnostics, Gazi-antep, TR) was used to determine the plasma TOS, following the provider’s directions. This test is found on the oxidation of the ferrous ion (Fe2+)-chelator complex to ferric ion (Fe3+) by the oxidants present in the plasma. The Fe3 + and a chromogen develop a complex colored; the intensity of the color is directly proportional to the quantity of oxidizing molecules in the sample and is measured spectrophotometrically at 530 nm. Oxidative Stress Index (OSI) This index was estimated through the ratio of TOS and TAS concentration (TOS/TAS) [ 16 ]. Statistical analysis The results are presented as mean ± standard deviations; after verifying the data distribution, they were analyzed by ANOVA of repeated measures and paired t test with the IBM SPSS V 20 statistical program (Armonk, NY, USA). Effect size per group was determined using Eta squared (η2). To explain this test, a partial Eta squared val-ue close to 0.01 is considered low, 0.06 medium, and a value greater than 0.14 large. For all tests, statistical significance was set at a p < 0.05. The analysis of results was carried out by protocol. Results Table 1 shows the clinical and demographic characteristics of the participants; no significant differences were observed in any parameter. Placebo Group (n=14) Experimental Group (n=19) p value Gender Women Men 11(79%) 3 (21%) 15(79%) 4 (21%) 1.0 Age (years) 65.7 ± 6.6 64.9 ± 6.7 0.98 Weight (Kg) Basal Three-months 82.9 ± 1.6 81.9 ± 1.4 82.0 ± 1.9 81.5 ± 1.0 0.60 BMI Basal Three-months 31.6 ± 2.4 31.8± 2.9 31.8 ± 2.8 31.6± 2.7 0.47 SBP (mmHg) Basal Three-months 123 ± 2.9 124 ± 2.6 121 ± 2.2 121 ± 2.5 0.74 DBP (mmHg) Basal Three-month 81 ± 4 83 ± 4 86 ± 3 85 ± 5 0.67 Table 1. Biochemical parameters pre- and post-treatment. BMI, Body mass index; SBP, Systolic blood pressure; DBP, Diastolic blood pressure. Data are presented as means ± standard deviation. ANOVA of repeated measures test, significance level 95%. Baseline vs three months inter group p values. Regarding biochemical parameters, a statistically significant reduction in HbA1c was observed for the EG compared to the placebo group (EG baseline 8.9% ± 2.2 post 7.8% ± 2.0, vs PG baseline 8.1% ± 2.0 post 7.8% ± 1.7). There were no significant differences in any other biochemical marker (Table 2). Placebo Group (n=14) Experimental Group (n=19) p value Glucose (mg/dL) Basal Three-months 169 ± 79 181 ± 80 174 ± 76 160 ± 76 0.73 Triglycerides (mg/dL) Basal Three-months 144 ± 61 184 ± 124 148 ± 73 170 ± 94 0.57 Cholesterol (mg/dL) Basal Three-month 191 ± 46 210 ± 40 186 ± 31 197 ± 52 0.55 HDL-C (mg/dL) Basal Three-months 58 ± 12 60 ± 15 55 ± 11 54 ± 14 0.23 LDL (mg/dL) Basal Three-months 104 ± 33 115 ± 33 101 ± 26 107 ± 46 0.57 Urea (mg/dL) Basal Three-months 39 ± 14 34 ± 15 36 ± 18 39 ± 17 0.62 Uric acid (mg/dL) Basal Three-months 3.1 ± 0.9 3.3 ± 1.6 3.5 ± 1.4 3.7 ± 1.5 0.71 Creatinine (mg/dL) Basal Three-months 0.94 ± 0.32 0.90 ± 0.42 0.97 ± 0.33 0.90 ± 0.42 0.74 Albumin (g/dL) Basal Three-month 4.0 ± 0.4 4.2 ± 0.5 4.0 ± 0.3 4.1 ± 0.4 0.87 HbA1c (%) Basal Three-months 8.1 ± 2.0 7.8 ± 1.7 8.9 ± 2.2 7.8 ± 2.0 0.04 Table 2. Biochemical parameters pre- and post-treatment. Data are presented as means ± standard deviation. ANOVA of repeated measures test, significance level 95%. *Baseline vs three months inter group p values are shown. HbA1c: glycosylated hemoglobin. A statistically significant diminution in the oxidative damage markers LPO, PC, TOS and OSI was observed in the EG compared to PG. (LPO EG baseline 0.243 µmol/L ± 0.067, post 0.222 µmol/L ± 0.050 vs PG baseline 0.338 µmol/L ± 0.138, post 0.373 µmol/L ± 0.145; PC, EG baseline 29.4 µmol/L ± 10, post 19.2 µmol/L ± 6* vs PG baseline 29.5 µmol/L ± 10 post 29.4 µmol/L ± 15; TOS, EG baseline 6.0 µmol H 2 O 2 Equiv./L ± 2.6, post 3.1 µmol H 2 O 2 Equiv./L ± 1.8, vs PG baseline 5.3 µmol H 2 O 2 Equiv./L ± 2, post 5.4 µmol H 2 O 2 Equiv./L ± 3; OSI EG baseline 5.7 ±3.1 post 2.0 ± 1.1 vs PG baseline 6.2 ±3, post 5.5± 4); paired with a statistically significant increase in TAS (EG baseline 0.94 mmol/L ± 0.29 post 1.22 mmol/L ± 0.28 vs PG baseline 1.06 mmol/L ± 0.28 post 1.09 mmol/L ± 0.20). As well, the SOD activity decreased in the PG baseline 179 U/mL ± 8.6, post 167 U/mL ± 12.9 vs EG baseline 177 U/mL ± 13 post 179 U/mL ± 17) (Table 3). Placebo Group (n=14) Experimental Group (n=19) p value Lipoperoxides (µmol/L) Basal Three-months 0.338 ± 0.138 0.373 ± 0.145 0.243 ± 0.067 0.222 ± 0.050 0.01 Protein carbonylation (nmol/mg) Basal Three-months 29.5 ± 10 29.4± 15 29.4 ± 10 19.2 ± 6 0.04 TOS (µmol H 2 O 2 Equiv./L) Basal Three-months 5.3 ± 2 5.4± 3 6.0 ± 2.6 3.1 ± 1.8 0.02 OSI Basal Three-months 6.2 ±3 5.5± 4 5.7 ±3.1 2.0 ± 1.1 0.03 SOD (U/mL) Basal Three-months 179 ± 8.6 167 ± 12.9 177± 12.8 179 ± 16.8 0.03 GPx (U/L) Basal Three-months 7327 ± 2234 7473 ± 2192 5970 ± 2234 6802 ± 1942 0.11 Catalase activity (U/mL) Basal Three-months 190 ± 70 280 ± 150 280± 150 300 ± 130 0.49 SOD/GPx Basal Three-months 0.027 ± 0.008 0.024 ± 0.008 0.033 ± 0.01 0.029± 0.10 0.53 TAS (mmol/L) Basal Three-months 1.06 ± 0.28 1.09 ± 0.20 0.94 ± 0.29 1.22 ± 0.28 0.05 AOX GAP (µmol/L) Basal Three-months 473 ± 270 473 ± 208 358 ± 283 551 ± 193 0.71 Table 3. Oxidative stress markers and pre- and post-treatment.. Data are shown as means ± standard deviation. ANOVA of repeated measures test, significance level 95%. *Baseline vs three months inter group p values are shown. TOS: Total oxidant status, OSI: Oxidative stress index, SOD: superoxide dismutase activity, GPx: glutathione peroxidase activity, TAS: Total antioxidant status, AOX GAP: antioxidant gap. The percentage of statistically significant effects intra group on markers of oxida-tive stress was for EG: LPO − 8.6%, PC -34%, TOS − 48%, OSI − 64%, TAS + 30%, and AOx GAP + 54% (Fig. 2), and for PG: SOD (-6.7%) and CAT (+ 51%), (Fig. 3). Finally, regarding effect sizes, the results showed significant improvements with effect sizes from moderate to large in LPO, (η2 = 0.116), TAS (η2 = 0.335), AOX GAP (η2 = 0.306), PC (η2 = 0.628), TOS (η2 = 0.804), and OSI (η2 = 0.656) in EG. While in PG only for SOD (η2 = 0.415) and CAT (η2 = 0.492). Discussion DM2 is a metabolic disease whose control has become a challenge for health systems worldwide. The hyperglycemia that describes it is responsible for the development of sustained alterations that lead to the typical complications of this disease, such as micro and macroangiopathies, which makes this disease a health problem with high direct and indirect costs. Its prevalence is higher among the elderly, who, to maintain health or control their diseases, frequently resort to the use of naturopathic treatments, which is why formal research is essential [ 7 , 17 ]. In this regard, previous studies conducted in an older population with MetS have shown that consuming 1500 mg of Sechium edule fruit powder (three capsules per day) has a hypoglycemic effect; this has already been reported in various preclinical studies and is attributed to the activity of the various compounds present in this fruit [ 10 – 12 , 18 ]. In this study, we have observed that in patients with type 2 diabetes mellitus, this hypoglycemic effect also occurs after three months of consumption of the same dose since the percentage of HbA1c was significantly lower in the GE, and although, with respect to fasting glucose, the decrease was not statistically significant, the result is consistent since a tendency to decrease was observed; this difference between both pa-rameters may be due to their nature, since serum glucose is a less precise marker and presents greater variability while HbA1c is the marker of choice to assess patient con-trol for 90 days, considering the half-life of erythrocytes, so we assume that in a longer intervention and with a larger population, the dispersion would probably be reduced and it would be possible to observe the effect also in serum glucose levels. On the other hand, as mentioned, phytochemical analysis of the capsules has shown that they contain a high amount of bioactives, and given this varied combination, we hypothesize that the pharmacological effects result from their synergistic action. In this sense, regarding the mechanisms involved, there is abundant scientific literature that brings together evidence of the hypoglycemic effect of these biomolecules ; the most consistent ones will be described below [ 19 – 23 ]. Regarding flavonoids, it has been reported that quercetin has antidiabetic effects since it promotes insulin secretion, improves insulin resistance and maintains glucose homeostasis [ 24 ]. It has been shown to do so by various mechanisms, for example, promotes insulin expression and glucose-stimulated insulin secretion in INS1E (insulin-secreting rat insulinoma) cell; as well as significantly increase the insulin secretion of INS-1 pancreatic β cells by specific activation of extracellular signal-regulated kinase 1/2 (ERK1/2) [ 25 ]; it has also been shown that it activate the intracellular Ca2 + signaling pathway [ 26 , 27 ]. In addition, improves insulin response by upregulating the phosphorylation of insulin receptors (InsRs) and protein kinase (PK). [ 28 ]. In the liver of rats, induced AMPK activation, with the consequent reduction of glucose production principally by downregulating strategic glycogenic isoenzymes [ 29 ]. In addition, it stimulates the translocation of the glucose transporter type 4 (GLUT4) to the membrane in skeletal muscle cells of rats. It has been shown that quercetin regulates the activity of sirtuin 1 (SIRT1) so that it could stimulate glucose metabolism in adipocytes and liver. It has also been shown to inhibit inflammation and OxS [ 30 , 31 ]. Regarding rutin, the suggested mechanisms for its antihyperglycemic effect comprise blockage of tissue gluconeogenesis, a reduction in carbohydrate assimilation from the small intestine, an improvement in tissue glucose uptake, stimulation of insulin secretion from beta cells, and protection of Langerhans islets. Rutin also reduces the generation of sorbitol, reactive species, advanced glycation end-product precursors, and inflammatory interleukins [ 32 , 33 ]. Myricetin has been reported to diminish hyperglycemia by inhibiting carbohydrate assimilation by α-glucosidase and α-amylase and stimulating insulin secretion, acting as a GLP-1R agonist. Additionally, myricetin reduces complications through antioxidant and anti-inflammatory actions [ 34 , 35 ]. Phlorizin's fundamental pharmacological action is to produce renal glycosuria and avoid intestinal glucose absorption by suppressing sodium–glucose symporters in the proximal renal tubule and mucosa of the small intestine [ 36 ]. Regarding cucurbitacins, it has been shown that Cucurbitacin B could considera-bly decrease blood glucose in a diabetic mouse model. Its effect was principally realized by regulating the intestinal level of AMPK, stimulating the secretion of plasmatic glucagon-like peptide-1 and insulin, and then modifying mice's appetite and eating behavior [ 37 ]. Finally, deeming gallic acid has been reported to improve insulin sensitivity and glucose homeostasis in adipocytes. The mechanism is by activating PPAR- and promoting GLUT4 translocation. Besides, gallic acid could enhance insulin sensitivity by regulating Akt and AMPK signaling pathways, revealing the dual activation of Akt and AMPK. Furthermore, the hypoglycemic effects of GA might be mediated by the regulation of TNF-α and adipocytokines expression. Likewise, GA inhibits caspase-9-related cellular apoptosis, improving the cellular function [ 38 , 39 ]. Evidently, biomolecules share mechanisms of action, which allow us to assume that a synergistic effect is plausible. Also, in some cases, it is proposed that the hypoglycemic effect is associated with the antioxidant effect since the decrease in the oxidative environment favors a better functioning of the regulatory proteins involved in glucose metabolism. This proposition is consistent with our findings since, as can be seen, the antioxidant effect in those who consumed Sechium edule is evident and coincides with what was observed in previous studies in patients with MetS [ 11 , 40 – 44 ]. In this sense, in this investigation, we observed a clear pattern of decreased markers of oxidative damage to biomolecules in the EG, in whom there was a significant decrease in LPO, PC, TOS, and OSI, coupled with an increase in TAS. While in the PG, a decrease in SOD activity was observed, accompanied by a striking increase in catalase, which, considering the dynamic nature of the OxS process, allows us to suggest that in this group, the oxidative state associated with hyperglycemia was maintained, which implied a greater demand and wear of antioxidant enzymes. These effects can be verified by observing the percentage of change in the determined parameters. In the EG, the statistically significant decrease in LPO, PC, TOS, and OSI, together with the increase in TAS and the antioxidant gap, confirmed that there was an antioxidant effect, which was not present in the PG, in whom the decrease in SOD activity was evident, accompanied by an increase in CAT. These data coincide with the intra-group effect sizes, which range from moderate to large, in the same markers, consistently confirming the antioxidant effect of treatment with Sechium edule. Regarding the mechanisms that explain these findings, abundant evidence from cellular and preclinical studies generally demonstrates that flavonoids can reduce OxS, whether or not it is associated with hyperglycemia. Flavonoids are antioxidants owing to the number and arrangement of their phenolic hydroxyl groups bound to ring structures. Their capability to act as antioxidants by donating an electron to an oxidant significantly depends on the reduction potentials of their radicals and their availability of the radical. The mechanisms pointed out comprise direct scavenging of reactive species, stimulation of antioxidant enzymes, enhancement of metal-chelating activity, augmenting α-tocopheryl radical levels, blocking NADPH oxidases, restraining NO´s OxS, increasing uric acid concentration, and augmenting the antioxidant properties of low-molecular-weight antioxidants [ 44 – 49 ]. In this regard, concerning the effect observed on LPO, it has been suggested that its decrease may be related to the capacity of biomolecules to activate the Nuclear fac-tor erythroid 2-related factor 2 (Nrf2) pathway, which is a transcriptional factor that regulates the expression of genes that code for enzymes with antioxidant function. Both apigenin and lutein have been shown to activate this pathway. Lutein also provides cytoprotection and reduction of lipid peroxidation by exerting anti-inflammatory ef-fects through the negative regulation of Nuclear factor kappa B (NFκB) and cell death mechanisms in vitro models [ 50 – 51 ]. Besides, quercetin exerts its antioxidant effects by limiting the production of lipid peroxides, such as malondialdehyde (MDA) and thiobarbituric acid-reactive substances (TBARS), and by promoting the synthesis of endogenous antioxidants. It has been shown that quercetin might improve OxS stress in diabetic rats by scavenging oxygen free radicals [ 23 , 30 , 52 – 53 ]. It should be noted that previous studies by our research group have shown that the consumption of Sechium edule for six months (dose of 1.5 g/day) decreases the con-tent of LPO and 8-isoprostanes through the activation of the Nrf2 pathway in older adults with metabolic syndrome. Likewise, this effect coincides with that reported in preclinical studies [ 11 , 12 , 54 ]. On the other hand, regarding protein carbonylation, which presupposes non-enzymatic oxidative post-translational modification, around 36 carbonylated proteins have been detected in obese diabetic patients, which are involved in molecular signaling, angiogenesis, cell adhesion, and cytoskeletal remodeling [ 55 – 56 ], hence the importance of their oxidation and the relevance of the findings of the present study since we observed a reduction in the content of proteins carbonylated by 34% in EG, which has also been evidenced in shorter intervention times in patients with MetS [ 18 , 57 ]. Regarding the mechanism involved, it has been pointed out that apigenin is a bioactive compound with anti-obesity activity, which improves the activity of antioxidant enzymes and reduces oxidation at the protein level, an effect associated with a decrease in the frequency of the apoptosis-mediated cell death mechanism in β-pancreatic cells in patients with MetS [ 58 ]. Likewise, it has been reported that luteolin reduces protein oxidation and improves the intracellular redox state in vitro models [ 59 ]. In our study, the decrease in oxidative damage at the lipid and protein levels had a beneficial impact by reducing the total oxidative state (TOS) by 50% and the OSI by 65%. This finding is consistent with the effect observed at the extracellular level where we found a 30% increase in the total antioxidant capacity (TAS) and 54% in the antioxidant gap. These results can be explained by considering the variety of bioactive molecules found in the capsules and coincide with what has been reported by other authors since it has been shown that the different parts that make up the Sechium edule fruit, such as pulp, peel, leaves, seeds, and pedicel, have a high antioxidant potential [ 11 , 19 , 60 – 61 ]. Our results show that the DM2 group that consumed Sechium edule for three months presents better antioxidant protection, possibly modulated from transcriptional levels as previously reported, which leads to counteracting OxS. These results have been consistent with previous research reported by our working group [ 10 , 11 , 17 , 53 , 57 ]. These may be due to the bioactive compounds present in chayote, such as cucurbitacin, phenolic acids, and flavonoids, whose antioxidant effects have been widely reported [ 60 , 63 – 70 ]. In this sense, the antioxidant effect of flavonoids has been consistently reported, so much so that some authors even consider the use of these molecules as alternatives to assist in the treatment of diabetes, our results despite the limitations regarding the sample size and duration of the intervention, support the proposal of the consumption of Sechium edule in older adults with type 2 diabetes, since its effectiveness and safety already demonstrated in the treatment of metabolic syndrome is confirmed by our findings, also in patients with diabetes. The results of the present investigation, that is, the decrease in the percentage of HbA1c and the diminution of oxidation markers LPO, CP, TOS, and OSI, coupled with the increase in TAS and the antioxidant gap, suggest that the consumption of Sechium edule powder capsules had a hypoglycemic and antioxidant effect in older adults with DM2. Limitations and Strengths One of the main limitations of the study is that the sample size is not representative. However, it is an exploratory study, and our findings justify conducting further double-blind studies with representative samples. Furthermore, the results were analyzed per protocol, so future studies should conduct an intention-to-treat analysis. Likewise, to corroborate the effect of the supplement regardless of the patients' baseline medication, we propose to analyze the possible effect of the doses of both concomitant medications, even Sechium edule. Also, another limitation of this study is the gender disparity among participants, in this regard, we propose creating less disparate groups in future research to analyze the possible role of sex-related metabolic differences and their relationship with the effects of Sechium edule supplementation. Regarding the strengths of the research, we can highlight that the findings are consistent with previous publications by our research group. Abbreviations T2DM Type 2 diabetes mellitus OxO Oxidative stress MetS Metabolic syndrome HbA1c Hemoglobin A1c EDTA Ethylenediamine tetra acetic acid GPx Gluthatione peroxidase CAT Catalase TAS Total antioxidant status TOS Total oxidant status PC Protein carbonylation LPO Lipid peroxidation DNPH 2,4-dinitrophenylhydrazine TBARS Thiobarbituric Acid Reactive Substances MDA Malondialdehyde NaOH Sodium hydroxide H 2 O 2 Hydrogen peroxide TAS Total Antioxidant Status AOGAP Antioxidant gap OSI Oxidative Stress Index Declarations A cknowledgement The authors would like to thank to the GiSEM for the biological material (Sechium edule fruits) proportioned for the capsules. Statement of Ethics The study was conducted in accordance with the Declaration of Helsinki, it was reviewed and approved by the Ethics Committee of the “National Autonomous University of Mexico (UNAM)—Zaragoza Campus” (FESZ-CE/22-118-22). Consent to participate statement: Informed consent was obtained from all subjects involved in the study. The biological material Sechium edule var. nigrum spinosum used for the research comes from the GiSEM germplasm bank and has legal registration No. 1924/CHT-010-101109 in the National Catalog of Plant Varieties, under the National Seed Inspection and Certification Service (SNICS). Its collection has followed the protocol of the transfer agreement for materials for research purposes. It was not obtained from wild areas, nor does it affect rural inhabitants, in accordance with Official Mexican Norm NMX-FF-047-SCFI-2003. It is a variety developed by our research group using the stratified visual mass selection genetic improvement technique. Conflict of Interest Statement The authors have no conflicts of interest to declare. Funding Sources This work was supported by grants from the General Director of Academic Personnel Affairs, National Autonomous University of Mexico (DGAPA-UNAM) (PAPIIT IN223923). The funder had no role in the design, data collection, data analysis, and reporting of this study. Author Contributions V.M.M-N. Conceptualization and design of the study, revised the manuscript, and analyzed the data; L.D.B-P. Performed the study and wrote the manuscript; J.R-P. Conceptualization and design of the study, analyzed the data, and wrote the manuscript; D.H-Á.; T.L.A-U.; I.A-S.; J. C-I.; E.S-O. and G.G-G. performed the study and analyzed the data. L.D.B-P. and J.R-P contributed equally to the writing of the manuscript. All authors reviewed the final manuscript. 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07:09:54","extension":"xml","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":164963,"visible":true,"origin":"","legend":"","description":"","filename":"14a6c34dfd4241b48fca5b1743d714261structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-6935192/v1/ab3f364bfbc1457c562fcbb4.xml"},{"id":96242088,"identity":"fd1bd6b6-b945-4b87-990f-24eb485cd566","added_by":"auto","created_at":"2025-11-19 07:11:59","extension":"html","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":182004,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-6935192/v1/2005350f30eff78df788cbaf.html"},{"id":95894838,"identity":"bbba0784-8e1e-4b32-a734-fc60e2e97642","added_by":"auto","created_at":"2025-11-14 07:09:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":258025,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the participant monitoring process.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6935192/v1/2d7f06861c93933a966041f7.png"},{"id":95894836,"identity":"2dbfd41c-847d-4c95-b7ec-18856a6c9e1e","added_by":"auto","created_at":"2025-11-14 07:09:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":31894,"visible":true,"origin":"","legend":"\u003cp\u003ePercentage changes [Δ% = (Post–Pre)/Pre*100] in parameters in EG following three-month intervention, intra group analysis. Significant differences with baseline levels (*p \u0026lt; 0.05). LPO: lipoperoxides, PC: protein carbonylation, TOS: Total oxidant status, OSI: Oxidative stress index, SOD: superoxide dismutase, GPx: gluthatione peroxidase, CAT: catalase, TAS Total antioxidant, AOX GAP: antioxidant gap.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6935192/v1/7115b57897e34e523066e29a.png"},{"id":96242717,"identity":"bc705873-c7b6-4407-a4a6-27f0dc6014d3","added_by":"auto","created_at":"2025-11-19 07:14:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":28963,"visible":true,"origin":"","legend":"\u003cp\u003ePercentage changes [Δ% = (Post–Pre)/Pre*100] in parameters in PG following three month intervention, intra group analysis. Significant differences with baseline levels (*p \u0026lt; 0.05). LPO: lipoperoxides, PC: protein carbonylation, TOS: Total oxidant status, OSI: Oxidative stress index, SOD: superoxide dismutase, GPx: gluthatione peroxidase, CAT: catalase, TAS Total antioxidant, AOX GAP: antioxidant gap.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6935192/v1/b4458fbf9959dd8ed350c8a3.png"},{"id":98920920,"identity":"9d0f6843-01ec-4be2-9b16-5413ad1ce301","added_by":"auto","created_at":"2025-12-24 06:09:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1170519,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6935192/v1/fd65cf11-40d0-4863-9e0c-65e475a64b04.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sechium edule var. nigrum spinosum consumption has a hypoglycemic and antioxidant effect in older people diabetic","fulltext":[{"header":"Introduction","content":"\u003cp\u003eType 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic hyperglycemia secondary to defects in the action and production of insulin with alterations in the intermediate metabolism of lipids and proteins. Chronic hyperglycemia favors the development of oxidative stress (OxS), a biochemical alteration that occurs when the production of reactive species exceeds the antioxidant response capacity and oxidative damage to biomolecules occurs with modifications at the cellular, tissue, and systemic levels; this process is linked to pathophysiology of micro and macroangiopathies, typical complications of this disease [1,3]. Likewise, OxS has been pointed out as a condition present in aging, so older people with DM2 have greater OxS and susceptibility to damage [4].\u003c/p\u003e\n\u003cp\u003eGiven the high prevalence of this disease and the debilitating nature of its complications, it is considered a global health problem due to the high direct and indirect costs associated with its treatment [5]. In M\u0026eacute;xico, the prevalence is 18.3% in the adult population and increases to 37% among the population over 60; therefore, finding strategies that contribute to its treatment is a current issue [6]. In this sense, considering that a high percentage of older adults consume alternative natural treatments and based on the background (clinical and preclinical) that the bioactive compounds pre-sent in the \u003cem\u003eSechium edule\u003c/em\u003e fruit (flavonoids, phenolic acids, and cucurbitacins) have an antioxidant and hypoglycemic effect [7-9]. In this regard, our research group has consistently demonstrated that the consumption of \u003cem\u003eSechium edule\u003c/em\u003e (1.5g daily) in capsules has a hypoglycemic, antioxidant and anti-inflammatory effect in older adults with metabolic syndrome (MetS), in whom the reversal of the same has been observed because of the impact on the regulation of lipids, glucose and blood pressure. Likewise, in addition to the increase in the activity of antioxidant enzymes, the increased expression of their RNA and the erythroid factor Nrf2, regulator of the antioxidant response, was observed [10-12]. \u0026nbsp;These findings suggest that capsules have great potential for use in patients with T2DM, in whom any of these effects would be beneficial and would favor control. For this reason, the purpose of this study is to explore the effect of consuming the dry extract of \u003cem\u003eSechium edule\u003c/em\u003e in older adults with T2DM.\u003c/p\u003e\n"},{"header":"Methods","content":"\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\u003ch2\u003eExperimental design\u003c/h2\u003e\u003cp\u003eThe study population was recruited through an open call distributed by printed invitations (leaflets) and digitally (social networks) specifying the objectives of the study and the inclusion criteria, which were to be over 60 years of age, clinically diagnosed with T2DM, preferably without comorbidities, without renal damage nor glycemic unevenness (HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;11%) and under treatment with oral hypoglycemic agents, without antioxidant intake and without exercising in the three months before the intervention. The Research Bioethics and Biosafety Committee of the Faculty of Higher Studies Zaragoza approved the study UNAM (FESZ-CE/22-118-22).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eIntervention\u003c/h2\u003e\u003cp\u003eA population of n\u0026thinsp;=\u0026thinsp;60 adults over 60 years was recruited, of which 17 did not meet the inclusion criteria. A sample of n\u0026thinsp;=\u0026thinsp;43 older adults was studied. After signing the in-formed consent, they were randomly assigned to two groups: (i) experimental (EG) n\u0026thinsp;=\u0026thinsp;22, who consumed 1.5g of \u003cem\u003eSechium edule\u003c/em\u003e per day (three capsules of 500 mg) for three months, and (ii) placebo (PG) n\u0026thinsp;=\u0026thinsp;21 who consumed three placebo capsules of equal appearance, also for three months. A group was created via social media to maintain ongoing contact with participants and promote adherence. Participants were also scheduled to receive monthly appointments to deliver the treatment and receive feedback.\u003c/p\u003e\u003cp\u003eRegarding pharmacological treatment, they were instructed to continue their physician-prescribed treatment, diet, and regular physical activity during the intervention. Follow-up was conducted with monthly medical visits. All participants continued their oral hypoglycemic agent (metformin); none were prescribed insulin.\u003c/p\u003e\u003cp\u003eThrough the intervention, three individuals from the EG and seven from the PG dropped out of the intervention because of logistical questions, (change of address, medical appointments elsewhere on the same day as the sample collection, lack of a companion to attend appointments) so finally, the data from n\u0026thinsp;=\u0026thinsp;19 in the EG and n\u0026thinsp;=\u0026thinsp;14 in the GP were analyzed. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the study participants' flow (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe pharmaceutical design of the capsules was carried out at the Faculty of Higher Studies Zaragoza, the fruits of \u003cem\u003eSechium edule\u003c/em\u003e were donated by the Interdisciplinary Research Group on \u003cem\u003eS. edule\u003c/em\u003e in Mexico A.C. (GISeM), and the primary treatment (to produce the powder of \u003cem\u003eSechium edule\u003c/em\u003e) was carried out at Faculty of Higher Studies Zaragoza, using food grade equipment. Subsequently, manufacturing and packaging on a larger scale was carried out by a certified pharmaceutical company expert in nutraceuticals, which delivered the product in bottles containing 90 capsules, which is sufficient treatment for 30 days. The placebo capsules looked the same as those of \u003cem\u003eSechium edule\u003c/em\u003e but contained talc and lactose monohydrate (pharmaceutical grade) in accordance with the United States Pharmacopeia (USP) (Sigma, St. Louis, MO, USA, EE.UU.).\u003c/p\u003e\u003cp\u003ePhytochemical analysis of Sechium edule capsules revealed that they contained the following amounts of the bioactive compounds 0.71 \u0026micro;g cucurbitacin I, 6.11 \u0026micro;g cucurbitacin D, 89.9 \u0026micro;g cucurbitacin B and 154.8 \u0026micro;g of cucurbitacin E; about flavonoids, 0.014 \u0026micro;g of apigenin, 1.30 \u0026micro;g of quercetin, 2.38 \u0026micro;g of myricetin, 14.2 \u0026micro;g of phlorizin, 45.5 \u0026micro;g of rutin and 48.8 \u0026micro;g of naringenin; regarding phenolic acids contains 38.8 \u0026micro;g of gallic acid, 9.3 \u0026micro;g of caffeic, 8.7 \u0026micro;g of syringic acid, 7.0 \u0026micro;g of ferulic acid, 3.3 \u0026micro;g of protocatechuic, 1.4 \u0026micro;g of acid chlorogenic, 1.7 \u0026micro;g of p-coumaric acid and 0.11\u0026micro;g of p-hydroxybenzoic acid [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eBiochemical analysis\u003c/h3\u003e\n\u003cp\u003eSamples\u003c/p\u003e\u003cp\u003eAfter an 8-hour fast, the blood samples were taken by venipuncture into vacutainer/siliconized tubes without anticoagulant to get serum for the determinations of glucose, renal profile, and lipid profile; with ethylenediamine tetra acetic acid (EDTA) for the measurement of hemoglobin A1c (HbA1c) and heparinized tubes for OxS testing. 500 \u0026micro;L of whole heparinized blood was separated for superoxide dismutase (SOD), 75 \u0026micro;L for gluthatione peroxidase (GPx), 100 \u0026micro;L for catalase (CAT), 100 \u0026micro;L of heparinized plasma for total antioxidant status (TAS), 100 \u0026micro;L of heparinized plasma for total oxidant status (TOS), 100 \u0026micro;L of heparinized plasma for protein carbonylation (PC) and 500 \u0026micro;L for lipid peroxidation (LPO). SOD, CAT, TAS, TOS and GPx techniques were performed in 96-well plates, which were measured on a Multiskan Go reader (Thermo Scientific, Denver, CO, USA). Blood chemistry was performed using colorimetric techniques (Randox Laboratories Ltd., Antrim UK) on a Selectra Junior analyzer (Vital Scientific, Dieren, The Netherlands); glycosylated hemoglobin (HbA1c) was determined by an immunoturbidimetry technique (Spinreact, Spain) in the same analyzer. The coefficients of variation for all determinations (intra-assay and inter-assay) were less than 5%.\u003c/p\u003e\u003cp\u003eThe measurements were taken from all participants before and after three months of treatment.\u003c/p\u003e\u003cp\u003ePlasma Thiobarbituric Acid Reactive Substances (TBARS)\u003c/p\u003e\u003cp\u003eIn this determination, the reaction between thiobarbituric acid (TBA) (0.11 mol/L) (Sigma, St. Louis, MO, USA) and malondialdehyde (MDA) in acid conditions (phosphoric acid, H3PO4, 0.2 mol/L) (Sigma, St. Louis, MO, USA) produces a pink pigment (the adduct TBA-MDA) which absorbs at 535 nm. In this assay, the addition of butylated hydroxytoluene (BHT) (Sigma, St. Louis, MO, USA) (12.6 mM) prevents the amplification of the peroxidation. In this assay, 200\u0026micro;L of plasma, 25 \u0026micro;L of BHT, 200\u0026micro;L of H3PO4, and 25 \u0026micro;L of TBA were incubated at 90\u0026deg;C for 45 min. The mix was cooled in ice to end the reaction, then 500 \u0026micro;L of butanol (Sigma, St. Louis, MO, USA) and 50 \u0026micro;L of a saturated solution of sodium chloride (NaCl) (Sigma, St. Louis, MO, USA) were added. The product must be read at 535 and 572 nm to correct baseline absorption. A calibration curve was used for the quantification [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eProteins Carbonylation\u003c/p\u003e\u003cp\u003e2,4-dinitrophenylhydrazine (DNPH) (Sigma, St. Louis, MO, USA) test was carried out to quantify carbonylated proteins. For this technique, 20\u0026micro;L of heparinized plasma and 20 \u0026micro;L of DNPH (10 mM in 0.5 M H3PO4) were incubated for 10 min at room temperature with agitation, and 20 \u0026micro;L of 6 M sodium hydroxide (NaOH) was added. After 10 more minutes of incubation in the same conditions, absorbance was measured at 450 nm against a blank sample. Protein concentration was determined using a 1.41 mg/mL standard of bovine serum albumin (BSA) and commercial Bradford reagent (Bio-Rad, Hercules, CA, USA).\u003c/p\u003e\u003cp\u003eWhole Blood Superoxide Dismutase\u003c/p\u003e\u003cp\u003eIn this method, the xanthine and xanthine oxidase reactions produce superoxide radicals, which react with 2-(4-iodophenyl)-3-(4-nitrophenol)-5-phenyl-tetrazolium chloride and form the dye red formazan, which is read at 505 nm. The enzyme present in the sample inhibits this reaction. SOD activity was determined with a commercial kit (Randox Laboratories Ltd., Antrim, UK).\u003c/p\u003e\u003cp\u003eWhole blood Glutathione Peroxidase\u003c/p\u003e\u003cp\u003eGlutathione oxidation by cumene hydroperoxide is catalyzed by glutathione peroxidase in the presence of glutathione reductase and reduced nicotinamide adenine dinucleotide phosphate (NADPH). Oxidized glutathione is converted into the reduced form with the simultaneous oxidation of NADPH to NADP+. The absorbance decrease is measured at 340 nm (Randox Laboratories Ltd., Antrim, UK).\u003c/p\u003e\u003cp\u003eThe SOD/GPx ratio was calculated.\u003c/p\u003e\u003cp\u003eCatalase Activity\u003c/p\u003e\u003cp\u003eThe activity of the CAT enzyme was measured with a hydrogen peroxide (H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e) inhibition assay using H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e (Sigma, St. Louis, MO, USA) as a substrate. This was a spectrophotometric technique. 10 \u0026micro;l of heparinized total blood was incorporated into 190\u0026micro;L of working solution (0.1 M phosphate buffer and 20 mM H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e). Absorbance detection was performed at 240 nm, inspecting the waste away from the H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e concentration every 15 s for 2 min [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePlasma Total Antioxidant Status (TAS)\u003c/p\u003e\u003cp\u003eThis assay is founded on the generation of the ABTS\u0026thinsp;+\u0026thinsp;cation radical, from the reaction of 2,20-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) with metmyoglobin and H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e. The bluish-green coloration of this radical is inhibited by the antioxidants in the sample and is read at 600 nm (Randox Laboratories Ltd., Antrim, UK).\u003c/p\u003e\u003cp\u003eThe antioxidant gap (AOGAP) was calculated too. The following equation is used: AOGAP = (TAS mmol- [(albumin (mmol) * 0.69)\u0026thinsp;+\u0026thinsp;uric acid (mmol)] [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTotal oxidant status (TOS)\u003c/p\u003e\u003cp\u003eThe commercial kit (Rel Assay Diagnostics, Gazi-antep, TR) was used to determine the plasma TOS, following the provider\u0026rsquo;s directions. This test is found on the oxidation of the ferrous ion (Fe2+)-chelator complex to ferric ion (Fe3+) by the oxidants present in the plasma. The Fe3\u0026thinsp;+\u0026thinsp;and a chromogen develop a complex colored; the intensity of the color is directly proportional to the quantity of oxidizing molecules in the sample and is measured spectrophotometrically at 530 nm.\u003c/p\u003e\u003cp\u003eOxidative Stress Index (OSI)\u003c/p\u003e\u003cp\u003eThis index was estimated through the ratio of TOS and TAS concentration (TOS/TAS) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe results are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations; after verifying the data distribution, they were analyzed by ANOVA of repeated measures and paired t test with the IBM SPSS V 20 statistical program (Armonk, NY, USA). Effect size per group was determined using Eta squared (η2). To explain this test, a partial Eta squared val-ue close to 0.01 is considered low, 0.06 medium, and a value greater than 0.14 large. For all tests, statistical significance was set at a p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. The analysis of results was carried out by protocol.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv\u003e\n \u003cp\u003eTable\u0026nbsp;1 shows the clinical and demographic characteristics of the participants; no significant differences were observed in any parameter.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePlacebo Group\u003c/p\u003e\n \u003cp\u003e(n=14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eExperimental Group\u003c/p\u003e\n \u003cp\u003e(n=19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGender \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Women\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Men\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11(79%)\u003c/p\u003e\n \u003cp\u003e3 (21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15(79%)\u003c/p\u003e\n \u003cp\u003e4 (21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e65.7\u0026nbsp;±\u0026nbsp;6.6\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e64.9\u0026nbsp;±\u0026nbsp;6.7\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eWeight (Kg)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e82.9\u0026nbsp;±\u0026nbsp;1.6\u003c/p\u003e\n \u003cp\u003e81.9\u0026nbsp;±\u0026nbsp;1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e82.0\u0026nbsp;±\u0026nbsp;1.9\u003c/p\u003e\n \u003cp\u003e81.5\u0026nbsp;±\u0026nbsp;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31.6\u0026nbsp;±\u0026nbsp;2.4\u003c/p\u003e\n \u003cp\u003e31.8±\u0026nbsp;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31.8\u0026nbsp;±\u0026nbsp;2.8\u003c/p\u003e\n \u003cp\u003e31.6±\u0026nbsp;2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSBP (mmHg)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e123\u0026nbsp;±\u0026nbsp;2.9\u003c/p\u003e\n \u003cp\u003e124\u0026nbsp;±\u0026nbsp;2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e121\u0026nbsp;±\u0026nbsp;2.2\u003c/p\u003e\n \u003cp\u003e121\u0026nbsp;±\u0026nbsp;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDBP (mmHg)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e81\u0026nbsp;±\u0026nbsp;4\u003c/p\u003e\n \u003cp\u003e83\u0026nbsp;±\u0026nbsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e86\u0026nbsp;±\u0026nbsp;3\u003c/p\u003e\n \u003cp\u003e85\u0026nbsp;±\u0026nbsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.67\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\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Biochemical parameters pre- and post-treatment.\u003c/p\u003e\n\u003cp\u003eBMI, Body mass index; SBP, Systolic blood pressure; DBP, Diastolic blood pressure. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData are presented as means ± standard deviation. ANOVA of repeated measures test, significance level 95%. Baseline \u003cem\u003evs\u003c/em\u003e three months inter group p values. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRegarding biochemical parameters, a statistically significant reduction in HbA1c was observed for the EG compared to the placebo group (EG baseline 8.9% ± 2.2 post 7.8% ± 2.0, \u003cem\u003evs\u003c/em\u003e PG baseline 8.1% ± 2.0 post 7.8% ± 1.7). There were no significant differences in any other biochemical marker (Table\u0026nbsp;2).\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePlacebo Group\u003c/p\u003e\n \u003cp\u003e(n=14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eExperimental Group\u003c/p\u003e\n \u003cp\u003e(n=19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGlucose (mg/dL)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e169\u0026nbsp;±\u0026nbsp;79\u003c/p\u003e\n \u003cp\u003e181\u0026nbsp;±\u0026nbsp;80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e174\u0026nbsp;±\u0026nbsp;76\u003c/p\u003e\n \u003cp\u003e160\u0026nbsp;±\u0026nbsp;76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTriglycerides (mg/dL)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e144\u0026nbsp;±\u0026nbsp;61\u003c/p\u003e\n \u003cp\u003e184\u0026nbsp;±\u0026nbsp;124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e148\u0026nbsp;±\u0026nbsp;73\u003c/p\u003e\n \u003cp\u003e170\u0026nbsp;±\u0026nbsp;94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCholesterol (mg/dL)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e191\u0026nbsp;±\u0026nbsp;46\u003c/p\u003e\n \u003cp\u003e210\u0026nbsp;±\u0026nbsp;40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e186\u0026nbsp;±\u0026nbsp;31\u003c/p\u003e\n \u003cp\u003e197\u0026nbsp;±\u0026nbsp;52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHDL-C (mg/dL)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e58\u0026nbsp;±\u0026nbsp;12\u003c/p\u003e\n \u003cp\u003e60\u0026nbsp;±\u0026nbsp;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e55\u0026nbsp;±\u0026nbsp;11\u003c/p\u003e\n \u003cp\u003e54\u0026nbsp;±\u0026nbsp;14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLDL (mg/dL)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e104 ± 33\u003c/p\u003e\n \u003cp\u003e115 ± 33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e101 ± 26\u003c/p\u003e\n \u003cp\u003e107 ± 46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eUrea (mg/dL)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e39\u0026nbsp;±\u0026nbsp;14\u003c/p\u003e\n \u003cp\u003e34\u0026nbsp;±\u0026nbsp;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e36\u0026nbsp;±\u0026nbsp;18\u003c/p\u003e\n \u003cp\u003e39\u0026nbsp;±\u0026nbsp;17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eUric acid (mg/dL)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.1\u0026nbsp;±\u0026nbsp;0.9\u003c/p\u003e\n \u003cp\u003e3.3\u0026nbsp;±\u0026nbsp;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.5\u0026nbsp;±\u0026nbsp;1.4\u003c/p\u003e\n \u003cp\u003e3.7\u0026nbsp;±\u0026nbsp;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.94\u0026nbsp;±\u0026nbsp; \u0026nbsp; \u0026nbsp;0.32\u003c/p\u003e\n \u003cp\u003e0.90\u0026nbsp;±\u0026nbsp; \u0026nbsp; \u0026nbsp;0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.97\u0026nbsp;±\u0026nbsp; \u0026nbsp; \u0026nbsp;0.33\u003c/p\u003e\n \u003cp\u003e0.90\u0026nbsp;±\u0026nbsp; \u0026nbsp; \u0026nbsp;0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAlbumin (g/dL)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.0\u0026nbsp;±\u0026nbsp; \u0026nbsp; \u0026nbsp;0.4\u003c/p\u003e\n \u003cp\u003e4.2\u0026nbsp;±\u0026nbsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.0\u0026nbsp;±\u0026nbsp; \u0026nbsp; \u0026nbsp;0.3\u003c/p\u003e\n \u003cp\u003e4.1\u0026nbsp;±\u0026nbsp;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHbA1c (%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8.1\u0026nbsp;±\u0026nbsp;2.0\u003c/p\u003e\n \u003cp\u003e7.8\u0026nbsp;±\u0026nbsp;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8.9\u0026nbsp;±\u0026nbsp;2.2\u003c/p\u003e\n \u003cp\u003e7.8\u0026nbsp;±\u0026nbsp;2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.04\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\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Biochemical parameters pre- and post-treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData are presented as means ± standard deviation. ANOVA of repeated measures test, significance level 95%. *Baseline \u003cem\u003evs\u003c/em\u003e three months inter group p values are shown. HbA1c: glycosylated hemoglobin.\u003c/p\u003e\n\u003cp\u003eA statistically significant diminution in the oxidative damage markers LPO, PC, TOS and OSI was observed in the EG compared to PG. (LPO EG baseline 0.243 µmol/L ± 0.067, post 0.222 µmol/L ± 0.050 \u003cem\u003evs\u003c/em\u003e PG baseline 0.338 µmol/L ± 0.138, post 0.373 µmol/L ± 0.145; PC, EG baseline 29.4 µmol/L ± 10, post 19.2 µmol/L ± 6* \u003cem\u003evs\u003c/em\u003e PG baseline 29.5 µmol/L ± 10 post 29.4 µmol/L ± 15; TOS, EG baseline 6.0 µmol H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e Equiv./L ± 2.6, post 3.1 µmol H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e Equiv./L ± 1.8, \u003cem\u003evs\u003c/em\u003e PG baseline 5.3 µmol H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e Equiv./L ± 2, post 5.4 µmol H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e Equiv./L ± 3; OSI EG baseline 5.7 ±3.1 post 2.0 ± 1.1 \u003cem\u003evs\u003c/em\u003e PG baseline 6.2 ±3, post 5.5± 4); paired with a statistically significant increase in TAS (EG baseline 0.94 mmol/L ± 0.29 post 1.22 mmol/L ± 0.28 \u003cem\u003evs\u003c/em\u003e PG baseline 1.06 mmol/L ± 0.28 post 1.09 mmol/L ± 0.20). As well, the SOD activity decreased in the PG baseline 179 U/mL ± 8.6, post 167 U/mL ± 12.9 \u003cem\u003evs\u003c/em\u003e EG baseline 177 U/mL ± 13 post 179 U/mL ± 17) (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePlacebo Group\u003c/p\u003e\n \u003cp\u003e(n=14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eExperimental Group\u003c/p\u003e\n \u003cp\u003e(n=19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLipoperoxides (µmol/L)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.338\u0026nbsp;±\u0026nbsp;0.138\u003c/p\u003e\n \u003cp\u003e0.373\u0026nbsp;±\u0026nbsp;0.145\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.243\u0026nbsp;±\u0026nbsp;0.067\u003c/p\u003e\n \u003cp\u003e0.222\u0026nbsp;±\u0026nbsp;0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eProtein carbonylation (nmol/mg)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29.5\u0026nbsp;±\u0026nbsp;10\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 29.4± 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29.4\u0026nbsp;±\u0026nbsp;10\u003c/p\u003e\n \u003cp\u003e19.2\u0026nbsp;±\u0026nbsp;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTOS (µmol H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e Equiv./L)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5.3\u0026nbsp;±\u0026nbsp;2\u003c/p\u003e\n \u003cp\u003e5.4±\u0026nbsp;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6.0\u0026nbsp;±\u0026nbsp;2.6\u003c/p\u003e\n \u003cp\u003e3.1\u0026nbsp;±\u0026nbsp;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eOSI\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6.2\u0026nbsp;±3\u003c/p\u003e\n \u003cp\u003e5.5±\u0026nbsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5.7\u0026nbsp;±3.1\u003c/p\u003e\n \u003cp\u003e2.0\u0026nbsp;±\u0026nbsp;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSOD (U/mL)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e179\u0026nbsp;±\u0026nbsp;8.6\u003c/p\u003e\n \u003cp\u003e167\u0026nbsp;±\u0026nbsp;12.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e177±\u0026nbsp;12.8\u003c/p\u003e\n \u003cp\u003e179\u0026nbsp;±\u0026nbsp;16.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGPx (U/L)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7327\u0026nbsp;±\u0026nbsp;2234\u003c/p\u003e\n \u003cp\u003e7473\u0026nbsp;±\u0026nbsp;2192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5970\u0026nbsp;±\u0026nbsp;2234\u003c/p\u003e\n \u003cp\u003e6802\u0026nbsp;±\u0026nbsp;1942\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCatalase activity (U/mL)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e190\u0026nbsp;±\u0026nbsp;70\u003c/p\u003e\n \u003cp\u003e280\u0026nbsp;±\u0026nbsp;150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e280±\u0026nbsp;150\u003c/p\u003e\n \u003cp\u003e300\u0026nbsp;±\u0026nbsp;130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSOD/GPx\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.027\u0026nbsp;±\u0026nbsp;0.008\u003c/p\u003e\n \u003cp\u003e0.024\u0026nbsp;±\u0026nbsp;0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.033\u0026nbsp;±\u0026nbsp;0.01\u003c/p\u003e\n \u003cp\u003e0.029±\u0026nbsp;0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTAS (mmol/L)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.06\u0026nbsp;±\u0026nbsp;0.28\u003c/p\u003e\n \u003cp\u003e1.09\u0026nbsp;±\u0026nbsp;0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.94 \u0026nbsp;± 0.29\u003c/p\u003e\n \u003cp\u003e1.22 ± 0.28\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAOX GAP (µmol/L)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Basal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Three-months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e473\u0026nbsp;±\u0026nbsp;270\u003c/p\u003e\n \u003cp\u003e473\u0026nbsp;±\u0026nbsp;208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e358\u0026nbsp;±\u0026nbsp;283\u003c/p\u003e\n \u003cp\u003e551\u0026nbsp;±\u0026nbsp;193\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.71\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\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e Oxidative stress markers and pre- and post-treatment..\u003c/p\u003e\n\u003cp\u003eData are shown as means ± standard deviation. ANOVA of repeated measures test, significance level 95%. *Baseline \u003cem\u003evs\u003c/em\u003e three months inter group p values are shown. TOS: Total oxidant status, OSI: Oxidative stress index, SOD: superoxide dismutase activity, GPx: glutathione peroxidase activity, TAS: Total antioxidant status, AOX GAP: antioxidant gap.\u003c/p\u003e\n\u003cp\u003eThe percentage of statistically significant effects intra group on markers of oxida-tive stress was for EG: LPO − 8.6%, PC -34%, TOS − 48%, OSI − 64%, TAS + 30%, and AOx GAP + 54% (Fig.\u0026nbsp;2), and for PG: SOD (-6.7%) and CAT (+ 51%), (Fig.\u0026nbsp;3).\u003c/p\u003e\n\u003cp\u003eFinally, regarding effect sizes, the results showed significant improvements with effect sizes from moderate to large in LPO, (η2 = 0.116), TAS (η2 = 0.335), AOX GAP (η2 = 0.306), PC (η2 = 0.628), TOS (η2 = 0.804), and OSI (η2 = 0.656) in EG. While in PG only for SOD (η2 = 0.415) and CAT (η2 = 0.492).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDM2 is a metabolic disease whose control has become a challenge for health systems worldwide. The hyperglycemia that describes it is responsible for the development of sustained alterations that lead to the typical complications of this disease, such as micro and macroangiopathies, which makes this disease a health problem with high direct and indirect costs. Its prevalence is higher among the elderly, who, to maintain health or control their diseases, frequently resort to the use of naturopathic treatments, which is why formal research is essential [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn this regard, previous studies conducted in an older population with MetS have shown that consuming 1500 mg of Sechium edule fruit powder (three capsules per day) has a hypoglycemic effect; this has already been reported in various preclinical studies and is attributed to the activity of the various compounds present in this fruit [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In this study, we have observed that in patients with type 2 diabetes mellitus, this hypoglycemic effect also occurs after three months of consumption of the same dose since the percentage of HbA1c was significantly lower in the GE, and although, with respect to fasting glucose, the decrease was not statistically significant, the result is consistent since a tendency to decrease was observed; this difference between both pa-rameters may be due to their nature, since serum glucose is a less precise marker and presents greater variability while HbA1c is the marker of choice to assess patient con-trol for 90 days, considering the half-life of erythrocytes, so we assume that in a longer intervention and with a larger population, the dispersion would probably be reduced and it would be possible to observe the effect also in serum glucose levels.\u003c/p\u003e\u003cp\u003eOn the other hand, as mentioned, phytochemical analysis of the capsules has shown that they contain a high amount of bioactives, and given this varied combination, we hypothesize that the pharmacological effects result from their synergistic action. In this sense, regarding the mechanisms involved, there is abundant scientific literature that brings together evidence of the hypoglycemic effect of these biomolecules ; the most consistent ones will be described below [\u003cspan additionalcitationids=\"CR20 CR21 CR22\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Regarding flavonoids, it has been reported that quercetin has antidiabetic effects since it promotes insulin secretion, improves insulin resistance and maintains glucose homeostasis [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. It has been shown to do so by various mechanisms, for example, promotes insulin expression and glucose-stimulated insulin secretion in INS1E (insulin-secreting rat insulinoma) cell; as well as significantly increase the insulin secretion of INS-1 pancreatic β cells by specific activation of extracellular signal-regulated kinase 1/2 (ERK1/2) [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]; it has also been shown that it activate the intracellular Ca2\u0026thinsp;+\u0026thinsp;signaling pathway [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In addition, improves insulin response by upregulating the phosphorylation of insulin receptors (InsRs) and protein kinase (PK). [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In the liver of rats, induced AMPK activation, with the consequent reduction of glucose production principally by downregulating strategic glycogenic isoenzymes [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In addition, it stimulates the translocation of the glucose transporter type 4 (GLUT4) to the membrane in skeletal muscle cells of rats. It has been shown that quercetin regulates the activity of sirtuin 1 (SIRT1) so that it could stimulate glucose metabolism in adipocytes and liver. It has also been shown to inhibit inflammation and OxS [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRegarding rutin, the suggested mechanisms for its antihyperglycemic effect comprise blockage of tissue gluconeogenesis, a reduction in carbohydrate assimilation from the small intestine, an improvement in tissue glucose uptake, stimulation of insulin secretion from beta cells, and protection of Langerhans islets. Rutin also reduces the generation of sorbitol, reactive species, advanced glycation end-product precursors, and inflammatory interleukins [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMyricetin has been reported to diminish hyperglycemia by inhibiting carbohydrate assimilation by α-glucosidase and α-amylase and stimulating insulin secretion, acting as a GLP-1R agonist. Additionally, myricetin reduces complications through antioxidant and anti-inflammatory actions [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePhlorizin's fundamental pharmacological action is to produce renal glycosuria and avoid intestinal glucose absorption by suppressing sodium\u0026ndash;glucose symporters in the proximal renal tubule and mucosa of the small intestine [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRegarding cucurbitacins, it has been shown that Cucurbitacin B could considera-bly decrease blood glucose in a diabetic mouse model. Its effect was principally realized by regulating the intestinal level of AMPK, stimulating the secretion of plasmatic glucagon-like peptide-1 and insulin, and then modifying mice's appetite and eating behavior [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFinally, deeming gallic acid has been reported to improve insulin sensitivity and glucose homeostasis in adipocytes. The mechanism is by activating PPAR- and promoting GLUT4 translocation. Besides, gallic acid could enhance insulin sensitivity by regulating Akt and AMPK signaling pathways, revealing the dual activation of Akt and AMPK. Furthermore, the hypoglycemic effects of GA might be mediated by the regulation of TNF-α and adipocytokines expression. Likewise, GA inhibits caspase-9-related cellular apoptosis, improving the cellular function [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eEvidently, biomolecules share mechanisms of action, which allow us to assume that a synergistic effect is plausible. Also, in some cases, it is proposed that the hypoglycemic effect is associated with the antioxidant effect since the decrease in the oxidative environment favors a better functioning of the regulatory proteins involved in glucose metabolism. This proposition is consistent with our findings since, as can be seen, the antioxidant effect in those who consumed Sechium edule is evident and coincides with what was observed in previous studies in patients with MetS [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR41 CR42 CR43\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn this sense, in this investigation, we observed a clear pattern of decreased markers of oxidative damage to biomolecules in the EG, in whom there was a significant decrease in LPO, PC, TOS, and OSI, coupled with an increase in TAS. While in the PG, a decrease in SOD activity was observed, accompanied by a striking increase in catalase, which, considering the dynamic nature of the OxS process, allows us to suggest that in this group, the oxidative state associated with hyperglycemia was maintained, which implied a greater demand and wear of antioxidant enzymes.\u003c/p\u003e\u003cp\u003eThese effects can be verified by observing the percentage of change in the determined parameters. In the EG, the statistically significant decrease in LPO, PC, TOS, and OSI, together with the increase in TAS and the antioxidant gap, confirmed that there was an antioxidant effect, which was not present in the PG, in whom the decrease in SOD activity was evident, accompanied by an increase in CAT. These data coincide with the intra-group effect sizes, which range from moderate to large, in the same markers, consistently confirming the antioxidant effect of treatment with Sechium edule.\u003c/p\u003e\u003cp\u003eRegarding the mechanisms that explain these findings, abundant evidence from cellular and preclinical studies generally demonstrates that flavonoids can reduce OxS, whether or not it is associated with hyperglycemia. Flavonoids are antioxidants owing to the number and arrangement of their phenolic hydroxyl groups bound to ring structures. Their capability to act as antioxidants by donating an electron to an oxidant significantly depends on the reduction potentials of their radicals and their availability of the radical. The mechanisms pointed out comprise direct scavenging of reactive species, stimulation of antioxidant enzymes, enhancement of metal-chelating activity, augmenting α-tocopheryl radical levels, blocking NADPH oxidases, restraining NO\u0026acute;s OxS, increasing uric acid concentration, and augmenting the antioxidant properties of low-molecular-weight antioxidants [\u003cspan additionalcitationids=\"CR45 CR46 CR47 CR48\" citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn this regard, concerning the effect observed on LPO, it has been suggested that its decrease may be related to the capacity of biomolecules to activate the Nuclear fac-tor erythroid 2-related factor 2 (Nrf2) pathway, which is a transcriptional factor that regulates the expression of genes that code for enzymes with antioxidant function. Both apigenin and lutein have been shown to activate this pathway. Lutein also provides cytoprotection and reduction of lipid peroxidation by exerting anti-inflammatory ef-fects through the negative regulation of Nuclear factor kappa B (NFκB) and cell death mechanisms in vitro models [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eBesides, quercetin exerts its antioxidant effects by limiting the production of lipid peroxides, such as malondialdehyde (MDA) and thiobarbituric acid-reactive substances (TBARS), and by promoting the synthesis of endogenous antioxidants. It has been shown that quercetin might improve OxS stress in diabetic rats by scavenging oxygen free radicals [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIt should be noted that previous studies by our research group have shown that the consumption of Sechium edule for six months (dose of 1.5 g/day) decreases the con-tent of LPO and 8-isoprostanes through the activation of the Nrf2 pathway in older adults with metabolic syndrome. Likewise, this effect coincides with that reported in preclinical studies [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOn the other hand, regarding protein carbonylation, which presupposes non-enzymatic oxidative post-translational modification, around 36 carbonylated proteins have been detected in obese diabetic patients, which are involved in molecular signaling, angiogenesis, cell adhesion, and cytoskeletal remodeling [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e], hence the importance of their oxidation and the relevance of the findings of the present study since we observed a reduction in the content of proteins carbonylated by 34% in EG, which has also been evidenced in shorter intervention times in patients with MetS [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. Regarding the mechanism involved, it has been pointed out that apigenin is a bioactive compound with anti-obesity activity, which improves the activity of antioxidant enzymes and reduces oxidation at the protein level, an effect associated with a decrease in the frequency of the apoptosis-mediated cell death mechanism in β-pancreatic cells in patients with MetS [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. Likewise, it has been reported that luteolin reduces protein oxidation and improves the intracellular redox state in vitro models [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn our study, the decrease in oxidative damage at the lipid and protein levels had a beneficial impact by reducing the total oxidative state (TOS) by 50% and the OSI by 65%. This finding is consistent with the effect observed at the extracellular level where we found a 30% increase in the total antioxidant capacity (TAS) and 54% in the antioxidant gap. These results can be explained by considering the variety of bioactive molecules found in the capsules and coincide with what has been reported by other authors since it has been shown that the different parts that make up the Sechium edule fruit, such as pulp, peel, leaves, seeds, and pedicel, have a high antioxidant potential [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur results show that the DM2 group that consumed Sechium edule for three months presents better antioxidant protection, possibly modulated from transcriptional levels as previously reported, which leads to counteracting OxS. These results have been consistent with previous research reported by our working group [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. These may be due to the bioactive compounds present in chayote, such as cucurbitacin, phenolic acids, and flavonoids, whose antioxidant effects have been widely reported [\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e, \u003cspan additionalcitationids=\"CR64 CR65 CR66 CR67 CR68 CR69\" citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn this sense, the antioxidant effect of flavonoids has been consistently reported, so much so that some authors even consider the use of these molecules as alternatives to assist in the treatment of diabetes, our results despite the limitations regarding the sample size and duration of the intervention, support the proposal of the consumption of Sechium edule in older adults with type 2 diabetes, since its effectiveness and safety already demonstrated in the treatment of metabolic syndrome is confirmed by our findings, also in patients with diabetes.\u003c/p\u003e\u003cp\u003eThe results of the present investigation, that is, the decrease in the percentage of HbA1c and the diminution of oxidation markers LPO, CP, TOS, and OSI, coupled with the increase in TAS and the antioxidant gap, suggest that the consumption of Sechium edule powder capsules had a hypoglycemic and antioxidant effect in older adults with DM2.\u003c/p\u003e\u003cp\u003eLimitations and Strengths\u003c/p\u003e\u003cp\u003eOne of the main limitations of the study is that the sample size is not representative. However, it is an exploratory study, and our findings justify conducting further double-blind studies with representative samples. Furthermore, the results were analyzed per protocol, so future studies should conduct an intention-to-treat analysis. Likewise, to corroborate the effect of the supplement regardless of the patients' baseline medication, we propose to analyze the possible effect of the doses of both concomitant medications, even Sechium edule. Also, another limitation of this study is the gender disparity among participants, in this regard, we propose creating less disparate groups in future research to analyze the possible role of sex-related metabolic differences and their relationship with the effects of Sechium edule supplementation.\u003c/p\u003e\u003cp\u003eRegarding the strengths of the research, we can highlight that the findings are consistent with previous publications by our research group.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eT2DM \u0026nbsp; Type 2 diabetes mellitus\u003c/p\u003e\n\u003cp\u003eOxO \u0026nbsp; \u0026nbsp; \u0026nbsp;Oxidative stress \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMetS \u0026nbsp; \u0026nbsp; Metabolic syndrome\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHbA1c \u0026nbsp; Hemoglobin A1c\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEDTA \u0026nbsp; \u0026nbsp; Ethylenediamine tetra acetic acid \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGPx \u0026nbsp; \u0026nbsp; \u0026nbsp; Gluthatione peroxidase\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCAT \u0026nbsp; \u0026nbsp; \u0026nbsp; Catalase\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTAS \u0026nbsp; \u0026nbsp; \u0026nbsp; Total antioxidant status\u003c/p\u003e\n\u003cp\u003eTOS \u0026nbsp; \u0026nbsp; \u0026nbsp;Total oxidant status\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePC \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Protein carbonylation\u003c/p\u003e\n\u003cp\u003eLPO \u0026nbsp; \u0026nbsp; \u0026nbsp; Lipid peroxidation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDNPH \u0026nbsp; 2,4-dinitrophenylhydrazine\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTBARS \u0026nbsp;Thiobarbituric Acid Reactive Substances\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMDA \u0026nbsp; \u0026nbsp; Malondialdehyde\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNaOH \u0026nbsp; \u0026nbsp;Sodium hydroxide\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eH\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Hydrogen peroxide\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTAS \u0026nbsp; \u0026nbsp; \u0026nbsp;Total Antioxidant Status\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAOGAP Antioxidant gap\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOSI Oxidative Stress Index\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e\u003cstrong\u003ecknowledgement\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank to the GiSEM for the biological material (Sechium edule fruits) proportioned for the capsules.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e Statement of Ethics\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki, it\u0026nbsp;was reviewed\u003cem\u003e\u0026nbsp;\u003c/em\u003eand approved by the Ethics Committee of the “National Autonomous University of Mexico (UNAM)—Zaragoza Campus” (FESZ-CE/22-118-22).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent to participate statement: Informed consent was obtained from all subjects involved in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe biological material\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSechium edule var. nigrum spinosum\u003c/em\u003e used for the research comes from the GiSEM germplasm bank and has legal registration No. 1924/CHT-010-101109 in the National Catalog of Plant Varieties, under the National Seed Inspection and Certification Service (SNICS). Its collection has followed the protocol of the transfer agreement for materials for research purposes. It was not obtained from wild areas, nor does it affect rural inhabitants, in accordance with Official Mexican Norm NMX-FF-047-SCFI-2003. It is a variety developed by our research group using the stratified visual mass selection genetic improvement technique.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConflict of Interest Statement\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFunding Sources\u003c/p\u003e\n\u003cp id=\"_Toc472330568\"\u003eThis work was supported by grants from the General Director of Academic Personnel Affairs, National Autonomous University of Mexico (DGAPA-UNAM) (PAPIIT IN223923). The funder had no role in the design, data collection, data analysis, and reporting of this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eV.M.M-N. Conceptualization and design of the study, revised the manuscript, and analyzed the data; L.D.B-P. Performed the study and wrote the manuscript; J.R-P. Conceptualization and design of the study, analyzed the data, and wrote the manuscript; D.H-Á.; T.L.A-U.; I.A-S.; J. C-I.; E.S-O. and G.G-G. performed the study and analyzed the data. L.D.B-P. and J.R-P contributed equally to the writing of the manuscript. All authors reviewed the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author, [V.M.M.-N.], upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAbel, E.D. et al. 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(2023). doi: 10.1016/j.phrs.2022.106587.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Sechium edule, hypoglycemic, antioxidant, elderly, type 2 diabetes","lastPublishedDoi":"10.21203/rs.3.rs-6935192/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6935192/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eChronic hyperglycemia, characteristic of type 2 diabetes mellitus (DM2), promotes oxidative stress (OxS). Therefore, it is necessary to strengthen the antioxidant defenses of diabetic patients, especially the elderly. \u003cem\u003eSechium edule\u003c/em\u003e contains high amounts of bioactives, which possess hypoglycemic and antioxidant properties, so we aimed to determine its effects in older diabetic patients. A quasi-experimental study was carried out in 33 older diabetic adults: (i) placebo group (PG; n\u0026thinsp;=\u0026thinsp;14); (ii) experimental group (EG; n\u0026thinsp;=\u0026thinsp;19). Glycosylated hemoglobin (HbA1c), lipoperoxides (LPO), protein carbonylation (PC), Total Oxidant Status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), superoxide dismutase, glutathione peroxidase, and catalase enzyme activity were measured pre and post-intervention. In the EG, a statistically significant decrease in HbA1c was observed (EG baseline 8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2 post 7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0), as well as in LPO, PC, TOS and OSI (LPO baseline 0.243\u0026thinsp;\u0026plusmn;\u0026thinsp;0.067, post 0.222\u0026thinsp;\u0026plusmn;\u0026thinsp;0.050; PC baseline 29.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10, post 19.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6; TOS baseline 6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6, post 3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8; OSI baseline 5.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1 post 2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1); coupled with a significative increase in TAS (baseline 0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29 post 1.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28), modifications not observed in the PG. The results suggest Sechium edule has hypoglycemic and antioxidant effects.\u003c/p\u003e","manuscriptTitle":"Sechium edule var. nigrum spinosum consumption has a hypoglycemic and antioxidant effect in older people diabetic","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-14 07:09:49","doi":"10.21203/rs.3.rs-6935192/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9b86c9e8-b5ac-4264-a71e-f9c05db563be","owner":[],"postedDate":"November 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":57528653,"name":"Health sciences/Endocrinology"},{"id":57528654,"name":"Health sciences/Health care"},{"id":57528655,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-12-24T06:09:35+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-14 07:09:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6935192","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6935192","identity":"rs-6935192","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}