Evaluation of antidiabetic activity of dietary phenolic compound chlorogenic acid in streptozotocin induced diabetic rats: Molecular docking, molecular dynamics, in silico toxicity, in vitro and in vivo studies

• Published in: Computers in biology and medicine 2021-07, Vol.134, p.104462-104462, Article 104462
• Main Authors: Singh, Amit Kumar, Rana, Harvesh Kumar, Singh, Vishal, Chand Yadav, Tara, Varadwaj, Pritish, Pandey, Abhay Kumar
• Format: Article
• Language: English
• Subjects: ADMET; Albumins; Alkaline phosphatase; Amylases; Antidiabetics; Beans; Beverages; Bilirubin; Biocompatibility; Blood; Body weight; Chlorogenic acid; Cholesterol; Citrus fruits; Cocoa; Coffee; Complications; Creatinine; Diabetes; Diabetes mellitus; Drugs; Enzymes; Food; Fruits; Functional foods & nutraceuticals; Glucose; Glucosidase; Health risks; High density lipoprotein; Hyperglycemia; Hyperlipidemia; In vivo methods and tests; Insulin; Kinases; Ligands; Lipids; Metabolism; Molecular dynamics; Phenols; Polyphenols; Proteins; Simulation; Streptozocin; Streptozotocin; Tea; Toxicity; Transaminase; Urea; Uric acid; α-Amylase; α-Glucosidase
• ISSN: 0010-4825; 1879-0534
• DOI: 10.1016/j.compbiomed.2021.104462

Chlorogenic acid is amongst the well-known polyphenolic compounds being used in human food and beverages. Its presence has been reported in tea leaves, roasted green beans, coffee, cocoa, berry fruits, apples, citrus fruits, and pears. The present study aims to elucidate the effectiveness of chlorogenic acid on in silico and in vitro inhibition of glucose metabolising enzymes (α-amylase and α-glucosidase) and on blood-based markers associated with diabetic complications in vivo. Docking and molecular dynamics studies were performed using GLIDE (Schrodinger, LLC, NY, 2019-2) and Maestro-Desmond Interoperability Tools, version 4.1 (Schrödinger, NY, 2015), respectively. α-Amylase and α-glucosidase inhibitory activities of chlorogenic acid were measured in vitro. Diabetes was induced in adult Wistar rats by injecting streptozotocin (50 mg/kg). Biochemical assays were performed using standard kits. The in silico studies for α-amylase and α-glucosidase with chlorogenic acid suggested that the ligand was stable and strongly bound with the above-mentioned proteins. During in vitro studies, chlorogenic acid inhibited both the enzymes in a dose-dependent manner (5–30 μg/mL). In addition, chlorogenic acid treatment for 28 days significantly suppressed the increase in blood glucose, total cholesterol, triglyceride, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, γ-glutamyl transferase, alkaline phosphatase, total bilirubin, creatinine, urea, uric acid, and feed intake levels in diabetic rats. Chlorogenic acid also caused significant improvement in body weight, serum HDL-cholesterol, total protein, and albumin levels leading to betterment in atherogenic indices related to diabetes-associated cardiovascular risks. The findings indicated that chlorogenic acid inhibited α-amylase and α-glucosidase and significantly decreased diabetes associated hyperglycemia, hyperlipidemia, and hepatorenal damage, making it a possible functional food ingredient and drug candidate for the management of diabetes and related complications. [Display omitted] •Chlorogenic acid is a natural phenolic compound present in food and beverages.•It has shown potent in silico and in vitro inhibitory potential against carbohydrate metabolising enzymes (alpha-amylase and alpha-glucosidase).•Chlorogenic acid showed significant antihyperglycemic activity in streptozotocin induced diabetic rats suggesting its antidiabetic activity.•It also exhibited hepatoprotective and antiatherogenic ef