Pharmacological Evaluation of Anti-Diabetic Activity of Myricetin in Different Cell Lines (original) (raw)
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Journal of Functional Foods, 2020
Myricetin derivatives (F2) isolated from leaf extract of Syzygium malaccense (Malay apple) which contains myricitrin predominantly, could potentially serve as functional food ingredient based on previous findings. The present study aimed to investigate the protective effects of F2 against hyperglycemia-induced oxidative stress in ARPE-19 (retinal pigment epithelium) cells; a diabetic retinopathy (DR) model. F2 showed effective inhibition of advanced glycation end products (AGE) formation. The derivatives attenuated high glucose (30 mM)-induced stress condition in ARPE-19 cells by reducing intracellular reactive oxygen species (ROS). At transcriptional level, F2 activated Nrf2 pathway besides upregulating antioxidant enzymes and other protective factors. In addition, protective effect of F2 against formation of AGE correlated with its ability to downregulate gene expression of inflammatory factor, NFkB1 and receptor for AGE. The findings showed that F2 was effective in preventing oxidative damage-induced by high glucose in ARPE-19 and could be developed as an adjuvant to manage DR.
Cell Biochemistry and Function, 2019
Endothelial dysfunction is recognized as the initial detectable stage of cardiovascular disease, a serious complication of diabetes. In this study, we evaluated effects of myricetin on high glucose (HG)-elicited oxidative damage in human umbilical vein endothelial cells (HUVECs). The cells were pre-incubated with myricetin and then treated with HG to induce apoptosis. The effect of myricetin on viability was investigated by MTT assay. The levels of lipid peroxidation (LPO) were determined by thiobarbituric acid (TBA) method. The protein expression of Bax, Bcl-2 and caspase-3 was measured by western blot analysis. Moreover, the effect of myricetin on total antioxidant capacity (TAC) and total thiol molecules was also determined. Our results showed that myricetin was able to markedly restore the viability of endothelial cells under oxidative stress. Myricetin reduced HG-caused increase in LPO levels. Also, TAC and total thiol molecules were notably elevated by myricetin. Incubation with myricetin decreased the protein expression levels of Bax, whereas it increased the expression levels of the Bcl-2, compared with HG treatment alone. Furthermore, myricetin significantly decreased cleaved caspase-3 protein expression. It is concluded that myricetin may protect HUVECs from oxidative stress induced by HG via increasing cell TAC and reducing Bax/Bcl-2 protein ratio, and caspase-3 expression.
Potential antihyperglycaemic effect of myricetin derivatives from Syzygium malaccense
Journal of Functional Foods, 2016
Myricitrin, a flavonoid-3-O-glycoside, found present in many plant parts is reported to have the potential to serve as a functional food ingredient. In the present study, myricetin derivatives (F2) isolated from leaf extract of Syzygium malaccense, consisted of predominantly myricitrin (77%), were evaluated for in vitro anti-hyperglycaemic activity. The ability of the samples to inhibit carbohydrate hydrolyzing enzymes, stimulate adipogenesis, glucose uptake, adiponectin secretion and affect gene expression in differentiated 3T3-L1 pre-adipocytes was assessed. F2 significantly inhibited both α-glucosidase and α-amylase. It exhibited 'insulinlike' effects by enhancing accumulation of lipid, glucose uptake and adiponectin secretion by activating insulin signalling pathway similar to insulin. It upregulated Akt1 (protein kinase B), PPARγ (peroxisome proliferator activated receptor gamma) and Slc2a4 (glucose transporter) genes in addition to PRKAG2 (protein kinase, AMP activated) and adiponectin to stimulate glucose uptake. The above findings suggest that the myricetin derivatives may serve as functional food ingredient.
Myricetin bioactive effects: moving from preclinical evidence to potential clinical applications
BMC Complementary Medicine and Therapies
Several flavonoids have been recognized as nutraceuticals, and myricetin is a good example. Myricetin is commonly found in plants and their antimicrobial and antioxidant activities is well demonstrated. One of its beneficial biological effects is the neuroprotective activity, showing preclinical activities on Alzheimer, Parkinson, and Huntington diseases, and even in amyotrophic lateral sclerosis. Also, myricetin has revealed other biological activities, among them as antidiabetic, anticancer, immunomodulatory, cardiovascular, analgesic and antihypertensive. However, few clinical trials have been performed using myricetin as nutraceutical. Thus, this review provides new insights on myricetin preclinical pharmacological activities, and role in selected clinical trials.
International Journal of Pharmacy and Pharmaceutical Sciences, 2018
Objective: The investigation has been conducted to find out the threshold dose of ethyl acetate fraction prepared from aqueous-methanol (40:60) extract of seed of Myristica fragrans (Houtt.) from the dose dependent experiment by noting the remedial effects of the said fraction on different complications developed in streptozotocin induced diabetic rat. Methods: Diabetic condition was made by single intramascular injection of streptozotocin at a dose of 4 mg/0.1 ml citrate buffer/100 g body weight. Treatment was conducted at different doses for 28 d on diabetic rat. Efficacy of the fraction on fasting blood glucose (FBG) and serum insulin levels, activities of key carbohydrate metabolic enzymes such as hexokinase, glucose-6-phosphate dehydogenase, glucose-6-phosphatase of hepatic and skeletomuscular tissue as well as antioxidative enzymes like catalase, superoxide dismutase (SOD) in connection with the levels of oxidative stress end products such as thiobarbituric acid reactive substances (TBARS), conjugated diene (CD) in hepatic and renal tissue and gene expression of hexokinase-1, SOD, Bax, Bcl-2 in hepatic tissue were assessed. Results: After different doses of fraction treatment to the diabetic animals; FBG, serum insulin levels and activities of carbohydrate metabolic enzymes i.e. hexokinase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase were rectified towards the control at the level of p<0.05. There is a significant (p<0.05) recovery in the activities of antioxidant enzymes such as catalase and SOD in respect to the vehicle treated diabetic group. Oxidative stress end products such as CD and TBARS levels were increased significantly (p<0.05) in vehicle treated diabetic rats and was rectified significantly (p<0.05) after fraction treatment at the dose of 10 mg or 20 mg or 40 mg fraction treated group. Gene expression of hexokinase-1, superoxide dismutase, bax and bcl-2 was rectified towards vehicle treated control significantly at the level of p<0.05 after treatment of different doses of fractions to the diabetic animals. Conclusion: The study indicates that the seeds of Myristica fragrans at the dose of 20 mg/100 g body weight possess most effective outcome to manage diabetic disorders in streptozotocin induced diabetic rats.
international food research journal, 2021
Myricetin derivatives from Syzygium malaccense leaf extract are known to have numerous therapeutic efficacies but there is no documented evidence corroborating its safety. Therefore, the present work aimed to evaluate the safety profile of myricetin derivative-rich fraction (MD) from S. malaccense leaf extract through single and repetitive oral administration in C57BL/6J mice. In the acute toxicity study, mice were orally administered with MD at single doses of 25, 150, 500, and 1,500 mg/kg. Subsequently, a modified sub-chronic toxicity assessment was performed by administering 150 mg/kg MD orally for 16 weeks. In both acute and sub-chronic toxicity studies, there were no lethal effects and behavioural signs of toxicity observed. The body weight, food, and water intakes of mice were normal throughout the respective experimental periods. As compared to the respective control groups, MD caused a significant improvement in serum uric acid and aspartate aminotransferase levels. The histopathological analysis of MD-administered mice did not show any inflammation or cell death. The MD-treated mice showed significantly reduced protein carbonyl and lipid hydroperoxide levels in urine, liver, and kidney tissues. Taken together, the no-observed-adverse-effect level of MD was up to 1,500 mg/kg, and considered safe for oral consumption over relatively long durations with oxidative stress attenuating properties.
Oxidative Medicine and Cellular Longevity
Type 2 diabetes mellitus (T2DM) may occur via oxidative stress. Myricitrin is a plant-derived antioxidant, and its solid lipid nanoparticle (SLN) may be more potent. Hence, the present study was conducted to evaluate the effects of myricitrin SLN on streptozotocin-nicotinamide- (STZ-NA-) induced T2DM of the mouse and hyperglycemic myotube. In this experimental study, cold homogenization method was used to prepare SLN. Then, 120 adult male NMRI mice were divided into 7 groups: control, vehicle, diabetes (received STZ 65 mg/kg 15 min after injected NA 120 mg/kg), diabetes + SLN containing myricitrin 1, 3, and 10 mg/kg, and diabetes + metformin. For in vitro study, myoblast (C2C12) cell line was cultured and divided into 6 groups (n=3): control, hyperglycemia, hyperglycemia + SLN containing myricitrin 1, 3, and, 10 μM, and hyperglycemia + metformin. After the last nanoparticle treatment, plasma samples, pancreas and muscle tissues, and myotubes were taken for experimental assessments. ...
Molecular Vision, 2019
Purpose Oxidative stress is implicated in the etiology of diabetes and its debilitating complications, such as diabetic retinopathy (DR). Various flavonoids have been reported to be useful in reducing DR progression. Myricetin derivatives (F2) isolated from leaf extract of Syzygium malaccense have the potential to serve as functional food as reported previously. The present study was performed with the aim of determining the antioxidant potential and protective effect of myricetin derivatives (F2) isolated from leaf extract of S. malaccense against glucose oxidase (GO)-induced hydrogen peroxide (H2O2) production that causes oxidative stress in ARPE-19 (RPE) cells. Methods Antioxidant properties were assessed through various radical (DPPH, ABTS, and nitric oxide) scavenging assays and determination of total phenolic content and ferric reducing antioxidant power level. ARPE-19 cells were preincubated with samples before the addition of GO (to generate H2O2). Cell viability, change in ...
Protective Effect of Myricetin on Proteins and Lipids of Erythrocytes Membranes
Asian Journal of Biological Sciences, 2013
Myricetin (3, 5, 7-Trihydroxy-2-(3, 4, 5-trihydroxyphenyl)-4-chromenone), a naturally occurring flavonol, is a potent scavenger of reactive oxygen species (ROS) and effectively prevent erythrocyte oxidation. The protective effect of myricetin on proteins and lipids of erythrocytes membranes was investigated. Erythrocytes membranes were subjected to oxidative stress by incubating them with 10 −5 M tert-butylhydroperoxide; this caused a significant increase in membrane protein carbonyl group content and membrane lipid peroxides while caused a significant decrease of membrane total thiol group and Na + , K +-ATPase activity. The presence of myricetin in micromolar concentration in the incubation medium decreased significantly protein carbonylation, lipid peroxidation and caused an increase in total thiol group and Na + , K + ATP-ase activity.