Cymbopogon citratus (DC.) Stapf mitigates ER-stress induced by streptozotocin in rats via down-regulation of GRP78 and up-regulation of Nrf2 signaling

• Published in: Journal of ethnopharmacology 2020-11, Vol.262, p.113130, Article 113130
• Main Authors: Elekofehinti, Olusola Olalekan, Onunkun, Afolashade Toritseju, Olaleye, Tolulope Mary
• Format: Article
• Language: English
• Subjects: Animals; Anti-diabetic herb; Apoptosis; C. citratus methanolic Extract; Cymbopogon; Diabetes mellitus; Down-Regulation - drug effects; Down-Regulation - physiology; Endoplasmic reticulum stress; Endoplasmic Reticulum Stress - drug effects; Endoplasmic Reticulum Stress - physiology; Heat-Shock Proteins - antagonists & inhibitors; Heat-Shock Proteins - metabolism; NF-E2-Related Factor 2 - agonists; NF-E2-Related Factor 2 - metabolism; Pancreas; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Leaves; Rats; Rats, Wistar; Signal Transduction - drug effects; Signal Transduction - physiology; Streptozocin - toxicity; Up-Regulation - drug effects; Up-Regulation - physiology
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2020.113130

Endoplasmic reticulum (ER) stress plays a role in the pathogenesis of diabetes mellitus, contributing to pancreatic dysfunction and insulin resistance. Ameliorating ER stress may be a viable therapeutic approach in the proper management of diabetes mellitus. Cymbopogon citratus (C.citratus) has been used in traditional medicine in the management of diabetes mellitus. Although well known for its anti-diabetic effect, the mechanism underlying this effect remains unclear. This study was designed to investigate the effect of C. citratus methanolic leaves extract on ER stress induced by streptozotocin (STZ) in wistar rats. STZ (60 mg/kg) was used to induce ER stress in the pancreas of rats. The rats were administered C. citratus methanolic leaves extract via gastric gavage at doses 100, 200 and 400 mg/kg for two weeks while metformin (100 mg/kg) was used as positive control. Fasting blood glucose (FBG), expression of ER-stress related genes (GRP78, CHOP, ATF4, TRB3, PERK, IRE1), antioxidant (Nrf2 and AhR) and pro-inflammatory (TNF-α) genes were determined. Possible compounds responsible for this effect were also predicted through molecular docking. Induction of ER stress using STZ significantly increased FBG while administration of C. citratus methanolic extract restored it to normal control level (p