Dual actions of gallic acid and andrographolide trigger AdipoR1 to stimulate insulin secretion in a streptozotocin-induced diabetes rat model

Tet Soon Wong; Fatahiya Mohamed Tap; Zanariah Hashim; Fadzilah Adibah Abdul Majid; Nor Hafizah Zakaria; Parsaoran Siahaan; Abeer Mogadem

doi:10.1016/j.jtcme.2022.09.002

Dual actions of gallic acid and andrographolide trigger AdipoR1 to stimulate insulin secretion in a streptozotocin-induced diabetes rat model

J Tradit Complement Med. 2022 Sep 28;13(1):11-19. doi: 10.1016/j.jtcme.2022.09.002. eCollection 2023 Jan.

Authors

Tet Soon Wong¹, Fatahiya Mohamed Tap², Zanariah Hashim¹, Fadzilah Adibah Abdul Majid^{3

4}, Nor Hafizah Zakaria³, Parsaoran Siahaan⁴, Abeer Mogadem⁵

Affiliations

¹ School of Chemical and Energy Engineering, Universiti Teknologi Malaysia, 81310, Johor, Malaysia.
² School of Chemical Engineering, College of Engineering, Universiti Teknologi MARA Bukit Besi, 23200, Dungun, Terengganu, Malaysia.
³ Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030, Kuala Nerus, Terengganu, Malaysia.
⁴ Department of Chemistry, Diponegoro University, Semarang, Indonesia.
⁵ Chemistry Department, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia.

Abstract

Common treatments for the management of diabetes have limitations due to side effects, hence the need for continuous research to discover new remedies with better therapeutic efficacy. Previously, we have reported that the combination treatment of gallic acid (20 mg/kg) and andrographolide (10 mg/kg) for 15 days demonstrated synergistic hypoglycemic activity in the streptozotocin (STZ)-induced insulin-deficient diabetes rat model. Here, we attempt to further elucidate the effect of this combination therapy at the biochemical, histological and molecular levels. Our biochemical analyses showed that the combination treatment significantly increased the serum insulin level and decreased the total cholesterol and triglyceride level of the diabetic animals. Histological examinations of H&E stained pancreas, liver, kidney and adipose tissues of combination-treated diabetic animals showed restoration to the normalcy of the tissues. Besides, the combination treatment significantly enhanced the level of glucose transporter-4 (GLUT4) protein expression in the skeletal muscle of treated diabetic animals compared to single compound treated and untreated diabetic animals. The molecular docking analysis on the interaction of gallic acid and/or andrographolide with the adiponectin receptor 1 (AdipoR1), a key component in the regulation of pancreatic insulin secretion, revealed a greater binding affinity of AdipoR1 to both compounds compared to individual compounds. Taken together, these findings suggest the combination of gallic acid and andrographolide as a potent therapy for the management of diabetes mellitus.

Keywords: AGP, Andrographolide; AdipoR1, Adiponectin receptor 1; Andrographolide; Diabetes mellitus; ELISA, Enzyme-linked immunosorbent assay; GA, Gallic acid; GLUT4, Glucose transporter-4; Gallic acid; H&E, Hematoxylin-eosin; Insulin; PBS, Phosphate buffer saline; STZ, Streptozotocin; TBST, Tris-buffered saline with 0.1% (v/v) Tween-20; adipoR1.