Modulation of opening of rat Liver mitochondrial membrane permeability transition pore by different fractions of the leaves of Cnestis ferruginea. D.C.

Abstract

Background: Increased attention is now directed towards the search for novel naturally occurring anticancer agents that can induce mitochondrial membrane permeability transition (MMPT) pore opening and cell death as a chemotherapeutic mechanism to combat cancer incidence. Aim: The inductive effects of partially purifiedfractions of leaves of Cnestis ferruginea- on rat liver MMPT pore opening was investigated. Method: De-fatted methanol extract of leaves of Cnestisferruginea was partitioned between water, chloroform, ethylacetate, or butanol separately in succession. The extract solutions were concentrated at 40°C to obtain water (WF), chloroform (CF), ethylacetate (EF) and butanol (BF) fractions. The effects ofthese fractions(0.2 - 1.4 mg/ml) on MMPT pore opening or mitochondrial swelling in the presence and absence of calcium were evaluated The effects of these fractions on the rat liver mitochondrial F0F,-ATPase activity were also assessed. Results: Ca2+-induced MMPT pore opening was inhibited by 1 mg/ml each of MECF, CF, BF, W F and EF by 75.0%, 83.0%, 88.0%, 68.0%, and 71.0%, respectively and compared with the effect of spermine, a standard inhibitor. However, in the absence of C a 2 \ the fractions significantly induced MMP T pore opening in intact mitochondria by 7.0, 5.7, 0.7, 4.8,10.9 folds, respectively. In normal rat liver mitochondria, F,F0-ATPase activity was stimulated maximally by MECF, CF, EF, BF and WF by 4.7, 12.7. 1.6. 3.6 and 1.5 folds, respectively, thus indicating that the chloroform fraction is the most potent and therefore contains the active principle in the plant. Conclusion: The present study revealed that the leaves of Cnestisferruginea contain bioactive substances that induced mitochondrial membrane permeability transition and activated the specific activity of F0F, ATPase. Thus, suggesting strongly that these bioactive agents may serve as a useful chemotherapeutic strategy in cancer therapy.