Gliclazide and Crassocephalum rubens leaf extract inhibit glucose-induced mitochondrial permeability transition pore (MPTP) opening in isolated pancreas mitochondria of Wistar rats

Abstract

Introduction: Mitochondrial permeability transition pore (MPTP) has been implicated in a wide variety of diseases such as cancer, neurodegenerative diseases, and diabetes. Crassocephalum rubens is a leafy vegetable consumed in different parts of Africa for the management of symptoms of diabetes mellitus, inflammation, malaria, and blood pressure. The present study evaluated the modulatory effects of aqueous leaf extract of C. rubens (ACR) and gliclazide on MPTP in the pancreas of Wistar albino rats in vitro. Methods: Pancreatic mitochondria were isolated from experimental animals using standard protocols. Furthermore, MPTP was induced using various concentrations (15, 22.5, 30, and 37.5 mmol/L) of glucose and CaCl2 (3 µM). Alterations in MPTP and ameliorative potential of different concentrations of ACR (8, 24, 40, 56 μg/mL) and gliclazide (0.054 mg/mL) were monitored spectrophotometrically via changes in absorbance at 540 nm for 12 minutes, under sodium succinate energized condition. Results: It was observed that 30 mmol/L, 37.5 mmol/L D-glucose, and Ca2+ significantly induced MPTP opening by 0.635, 5.10, and 9.95 folds, respectively, an effect that was reversed by gliclazide and ACR, in a none-dose dependent manner. In addition, ACR at 56 μg/mL in conjunction with Ca2+ opened the MPTP. Conclusion: Data from this study suggest that gliclazide and ACR, especially at the lower concentrations, possess significant inhibitory effects against MPTP opening in the pancreas of male Wistar albino rats and, therefore, could be useful in protecting beta-cell death usually associated with diabetes mellitus, as well as other conditions in which MPTP opening is implicated.

Keywords

• diabetes
• inflammation
• herbal medicine
• beta-cell
• apoptosis