Some Solvent Fractions of the Fruits of Xylopia aethiopica Enhance Mitochondrial-Mediated Apoptosis in Rat Liver

Abstract

The mitochondrial membrane Permeability Transition (mPT) pore has emerged as a promising target for drug development in diseases where there is dysregulation of apoptosis. In this study, the effects of various fractions of the methanol extract of Xylopia aethiopica (XA), a potent medicinal plant, were investigated on mitochondrial-mediated apoptosis. The methanol extract was partitioned in succession between dichloromethane, ethylacetate and methanol to obtain Dichloromethane (DFXA), Ethylacetate (EFXA) and Methanol (MFXA) fractions of the fruits. The effects of DFXA, the most potent fraction, on mPT pore, mitochondrial ATPase (mATPase), lipid peroxidation, DNA fragmentation, cytochrome c release and caspases 9 and 3 activities were estimated. Varying concentrations of DFXA (20, 60, 100, 140 and 180 μg/ml) significantly induced pore opening in the absence of calcium by 9.92, 12.36, 13.75, 14.92 and 15.47 folds, respectively. Similarly, Ca 2+-induced mPT pore opening was further enhanced by 8.3, 9.14, 10.5, 18.53 and 20.5 folds and mATPase activity was significantly elevated by these concentrations of DFXA. In contract, EFXA and MFXA did not have any significant effect at lower concentrations but induced pore opening at 180μg/ml by 1.69 and 6.4 folds, respectively. In vivo, DFXA caused the induction of mPT pore in the absence of calcium, activation of the activities of caspases 9 and 3, significant DNA fragmentation in a dose-dependent manner and also ameliorated ferrous-induced mitochondrial membrane lipid peroxidation. These findings reveal that the dichloromethane fraction of Xylopia aethjopica contains a bioactive agent capable of inducing mitochondrial-mediated apoptosis and may be useful for drug development in diseases where apoptosis is compromised.