Fractions of Adenopus breviflorus Extract Modulate Calcium-induced Mitochondrial Permeability Transition Pore Opening in Rat Liver

Abstract

Abstract Mitochondrial dysfunction (MD) and impaired apoptotic pathways cause irreversible opening of the Mitochondrial Permeability Transition (MPT) pore, resulting in several pathological conditions e.g. cancer, ageing and neurodegenerative diseases. Many bioactive compounds from plants have been identified as modulators of the MPT pore which makes them possible drugs for the management of MD associated diseases. Adenopus breviflorus (A.breviflorus) is a tropical medicinal plant used in folkore medicine as an abortifacient and in treating gonorrhoea. In this study, the effects of ethylacetate and methanol fractions of A.breviflorus were assessed on rat liver MPT pore and Mitochondrial ATPase (mATPase). The fruit of A.breviflorus was extracted with water to obtain the aqueous Extract (AEAB), which was fractionated using vacuum liquid chromatography (VLC) to obtain ethylacetate and methanol fractions of A.breviflorus (EFAB, and MFAB). The extent of MPT pore opening and mATPase by EFAB and MFAB were assayed spectrophotometrically. The results obtained showed that EFAB and MFAB have no significant inductive effect on the MPT pore in the absence of Ca2+. However, in the presence of Ca2+, EFAB inhibited calcium-induced MPT pore opening in a non-concentration dependent manner. Maximum inhibition of MPT pore opening was 57.1% at 50 μg/ml. Interestingly, MFAB potentiated calcium ion effect by opening the pore further. Specifically, MFAB opened the MPT pore by 11, 10, 17 and 9% at 50, 150, 250 and 350 μg/ml, respectively. Furthermore, EFAB and MFAB inhibited mATPase activity in rat liver mitochondria at 62.5, 187.5, 312.5 and 437.5 μg/ml by 2.6, 18.8, 37.3, 52.6% and 41.8, 6.8, 24.3, 8.4%, respectively. The ethylacetate and methanol fractions of Adenopus breviflorus possess potential phytochemicals that can modulate opening of the mitochondrial permeability transition pore and inhibit mitochondrial ATPase activity in rat liver. These fractions may find use in drug development against diseases where excessive apoptosis takes place.