Arbutin ameliorates hyperglycemia, dyslipidemia and oxidative stress and modulates adipocytokines and PPARγ in high-fat diet/streptozotocin-induced diabetic rats

• Published in: Life sciences (1973) 2023-05, Vol.321, p.121612-121612, Article 121612
• Main Authors: Abduh, Maisa Siddiq, Alzoghaibi, Mohammed A., Alzoghaibi, Abdullah M., Bin-Ammar, Albandari, Alotaibi, Mohammed F., Kamel, Emadeldin M., Mahmoud, Ayman M.
• Format: Article
• Language: English
• Subjects: Adipokines - metabolism; alpha-Glucosidases - metabolism; Animals; Arbutin; Arbutin - pharmacology; Arbutin - therapeutic use; Blood Glucose - metabolism; Diabetes; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - metabolism; Diet, High-Fat - adverse effects; Dyslipidemias - drug therapy; Dyslipidemias - metabolism; Glucose Intolerance; Glucose tolerance; Hexokinase - metabolism; Inflammation; Insulin - metabolism; Insulin Resistance; Liver Glycogen - metabolism; Oxidative Stress; PPAR gamma - metabolism; Rats; Resistin - metabolism; Resistin - pharmacology; Resistin - therapeutic use; Streptozocin - pharmacology
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2023.121612

Arbutin is a glycosylated hydroquinone with antioxidant and anti-hyperglycemia effects. However, its beneficial effects in type 2 diabetes (T2D) were not clarified. This study evaluated the effect of arbutin on hyperglycemia, dyslipidemia, insulin resistance, oxidative stress, and inflammatory response in T2D. Rats induced by high fat diet and streptozotocin were treated with arbutin (25 and 50 mg/kg) for 4 weeks. Diabetic rats exhibited glucose intolerance, elevated HbA1c%, reduced insulin, and high HOMA-IR. Liver glycogen and hexokinase activity were decreased in T2D rats while glucose-6-phosphatase (G6Pase), fructose-1,6- biphosphatase (FBPase), and glycogen phosphorylase were upregulated. Circulating and hepatic cholesterol and triglycerides and serum transaminases were elevated in T2D rats. Arbutin ameliorated hyperglycemia, dyslipidemia, insulin deficiency and resistance, and liver glycogen and alleviated the activity of carbohydrate-metabolizing enzymes. Both doses of arbutin decreased serum transaminases and resistin, and liver lipids, TNF-α, IL-6, malondialdehyde and nitric oxide, downregulated liver resistin and fatty acid synthase, and increased serum and liver adiponectin, and liver reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). These effects were associated with the upregulation of hepatic PPARγ. Arbutin inhibited α-glucosidase in vitro and in silico investigations revealed the ability of arbutin to bind PPARγ, hexokinase, and α-glucosidase. In conclusion, arbutin effectively ameliorated glucose intolerance, insulin resistance, dyslipidemia, inflammation, and oxidative stress, and modulated carbohydrate-metabolizing enzymes, antioxidants, adipokines and PPARγ in T2D in rats. •Arbutin ameliorates glucose intolerance and insulin resistance in type 2 diabetic rats.•Arbutin alleviates liver carbohydrate metabolizing enzymes in type 2 diabetic rats.•Arbutin prevents dyslipidemia and liver lipid accumulation.•Arbutin attenuates oxidative stress and inflammation in type 2 diabetic rats.•Arbutin modulates fatty acid synthase and PPARγ and inhibits α-glucosidase.