Evaluation of the Effects of Fractions of Jatropha curcas (Linn) Leaves on Mitochondrial Permeability Transition in Rat Liver
Olubukola T. Oyebode, Wuraola R. Owaboye, Opeyemi F. Akinbisoye, Olufunso O. Olorunsogo
Annual Research & Review in Biology · pp. 1–15 · Published 29 Aug 2017
10.9734/ARRB/2017/35882Abstract
Aim: Modulation of the opening of mitochondrial Permeability Transition (mPT) pore is an important pharmacological target in drug design because the release of cytochrome C upon the opening of the pore is sine qua non for mitochondrial-mediated apoptosis to take place. Jatropha curcas has been shown to inhibit the growth of tumorigenic cells in different cancer cells. It is not known whether the intrinsic pathway of apoptosis is implicated in the mechanism of action of J. curcas as an anti-tumour agent. This study evaluated the effects of varying concentrations of the methanol extract of Jatropha curcas and its fractions on mPT pore and cytochrome C release. Methodology: Mitochondrial permeability transition, mitochondrial lipid peroxidation, mitochondrial lipid peroxidation, cytochrome C release were evaluated spectrophotometrically. Results: Chloroform fraction of J. curcas (CFJC) significantly induced pore opening at 10, 30, 50, 70 and 90 µg/mL by 2.2, 3.5, 8.5, 11.0 and 11.7 folds, respectively in the absence of calcium when compared with other fractions. In contrast calcium -induced pore opening was inhibited by all the fractions. Interestingly, all the fractions also inhibited Fe2+-induced lipid peroxidation in a concentration-dependent manner. Mitochondrial ATPase activity was enhanced to varying extents by these fractions with CFJC having the highest stimulatory effects. The concentration of cytochrome C released from mitochondria exposed to CFJC at 10, 30, 50, 70 and 90µg/mL were significantly (p < 0.05) elevated by 5, 10, 12.5, 14.2 and 17 folds, respectively when compared with control. Conclusion: These findings suggest that CFJC, the most potent fraction may contain certain bioactive agent(s) that modulates mPT pore opening and possibly induces mitochondrial-mediated apoptosis via release of cytochrome C and reduction of intracellular ATP levels. Jatropha curcas may therefore prove useful in drug development in diseases characterized by insufficient apoptosis.
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