Effect of Different Solvent Fractions of Sarcocephalus latifolius (Smith) Bruce on Rat Liver Mitochondrial Membrane Permeability Transition (mPT) Pore
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Abstract
Mitochondria are an essential pharmacological target for the development of cytotoxic drugs. Many bioactive agents of plant origin have been found to induce mitochondrial-mediated apoptosis via membrane permeability transition (mPT) pore, osmotic swelling and ultimately the release of cytochrome C. Sarcocephalus latifolius (SL) is used in folkloric medicine for the treatment of breast cancer, but there are no scientific data to support this claim. The study therefore evaluated the in vitro effects of Sarcocephalus latifolius (SL) fruits chloroform (CFSL), ethyl acetate (EFSL), and methanol (MFSL) fractions on rat liver mitochondria. Male Wistar rats with average weight of 90 ± 10 g were used for this study. Rat liver mitochondria were isolated by differential centrifugation. mPT pore opening, mitochondria ATPase activity, Fe2+-induced lipid peroxidation, and cytochrome C release were assayed spectrophotometrically at 540 nm, 660 nm, 532 nm, and 414 nm, respectively. In the absence of Ca2+, CFSL, EFSL, and MFSL induced mPT pore opening in a concentration-dependent manner, with CFSL exhibiting the highest activity. Interestingly, CFSL and EFSL inhibited lipid peroxidation, while MFSL induced lipid peroxidation in a concentration-dependent manner with CFSL showing the highest percentage inhibition of 90%. Mitochondrial ATPase activity and cytochrome C release were significantly enhanced by CFSL. These findings suggest that CFSL and EFSL contain certain bioactive agents that can induce mPT pore opening and subsequently result in mitochondrial-mediated apoptosis. This preliminary finding will serve as a template for drug development for ailments that require the up˗regulation of apoptosis.
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