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

Amit Kumar Singh; Harvesh Kumar Rana; Vishal Singh; Tara Chand Yadav; Pritish Varadwaj; Abhay Kumar Pandey

doi:10.1016/j.compbiomed.2021.104462

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

Comput Biol Med. 2021 Jul:134:104462. doi: 10.1016/j.compbiomed.2021.104462. Epub 2021 May 2.

Authors

Amit Kumar Singh¹, Harvesh Kumar Rana¹, Vishal Singh², Tara Chand Yadav³, Pritish Varadwaj², Abhay Kumar Pandey⁴

Affiliations

¹ Department of Biochemistry, University of Allahabad, Prayagraj, 211002, India.
² Bioinformatics Division, Indian Institute of Information Technology Allahabad, Prayagraj, 211015, India.
³ Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, 247667, India.
⁴ Department of Biochemistry, University of Allahabad, Prayagraj, 211002, India. Electronic address: akapndey23@rediffmail.com.

PMID: 34148008
DOI: 10.1016/j.compbiomed.2021.104462

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Result: 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.

Conclusion: 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.

Keywords: ADMET; Chlorogenic acid; Diabetes; Streptozotocin; α-amylase; α-glucosidase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chlorogenic Acid / pharmacology
Diabetes Mellitus, Experimental* / drug therapy
Glycoside Hydrolase Inhibitors
Hypoglycemic Agents* / pharmacology
Molecular Docking Simulation
Molecular Dynamics Simulation
Plant Extracts
Rats
Rats, Wistar
Streptozocin / toxicity

Substances

Glycoside Hydrolase Inhibitors
Hypoglycemic Agents
Plant Extracts
Chlorogenic Acid
Streptozocin