Induction of Mitochondrial Membrane Permeability Transition Pore Opening and DNA fragmentation by Solvent Fractions of Mangifera indica

Abstract

The opening of mitochondrial permeability transition (mPT) pore is a crucial step for apoptotic cell death. Certain bioactive agents in medicinal plants elicit their chemo-protective effect against tumor via the induction of the mPT pore opening. This study therefore investigated the effects of different solvent fractions of Mangifera indica on mitochondrial-mediated apoptosis via mPT pore opening to ascertain the most potent fraction. Methanol extract of Mangifera indica was partitioned successively to obtain n-hexane (NFMI), dichloromethane (DFMI), ethylacetate (EFMI) and methanol (MFMI) fractions. Rat liver and uterine mitochondria were isolated by differential centrifugation. The effects of DFMI, EFMI and MFMI on mPT pore, cytochrome c release, mitochondrial ATPase activity, lipid peroxidation and hepatic and uterine DNA fragmentation were assessed spectrophotometrically while caspases 9 and 3 activities were determined using ELISA technique. The in vitro results showed that there was a concentration-dependent induction of mPT pore opening by MFMI and EFMI. However, MFMI was more potent than EFMI while DFMI did not have any effect. Similar pattern of results were recorded on cytochrome c release and mitochondrial ATPase activity. The in vivo results on mPT pore also showed MFMI to be the most potent, followed by EFMI while DFMI had no effect. The results on DNA fragmentation and caspases also showed MFMI to be the most potent of the three solvent fractions. The results of this study suggest that MFMI is the most potent containing the bioactive agents that may induce mitochondrial-mediated apoptosis.