Investigating the Modulatory Effect of Methanol Extract of Daniellia oliveri (ROLFE) Leaves on Mitochondrial Membrane Permeability Transition (MPT) Pore

Abstract

Background: Mitochondrial-mediated cell death begins with opening of mitochondrial membrane permeability transition (mPT) pore and medicinal plants contain phytochemicals that modulate the mPT pore.
 Hypothesis and Purpose: We investigated the modulatory effects of crude methanol extract of Daniellia oliveri leaves (CMDO) on mPT pore in vitro.
 Study Design and Methods: Phytochemical screening and antioxidant activities of crude methanol extract of Daniellia oliveri leaves (CMDO) were evaluated according to standard procedures. CMDO was partitioned into chloroform fraction (CFDO), ethyl acetate fraction (EFDO) and methanol fraction (MFDO) by Vacuum liquid chromatography (VLC). Effects of CMDO, CFDO, EFDO and MFDO on mPT pore were assessed by spectrophotometry. Effects of the most potent fraction on mitochondrial ATPase, Fe-induced lipid peroxidation and cytochrome c release were assessed by spectrophotometry. CMDO was subjected to GC-MS analysis to identify the bioactive compounds present.
 Results: CMDO contains phytochemicals and showed appreciable total flavonoid content (0.483±0.02 QE mg/100g), total phenolic content (0.886±0.12 GAE mg/100g), total antioxidant capacity (0.039±0.001 AE mg/100 g), ferric antioxidant reducing power (IC50=350 µg/ml) and 2, 2-diphenyl-1 picrylhydrazyl (DPPH) radical scavenging activity (IC50=166 µg/ml). The maximum induction of mPT pore opening in the absence and presence of calcium, respectively, were as follows: CMDO (10.11 folds, 5.18 folds), CFDO (19.9 folds, 16.3 folds), EFDO (7.5 folds, 23.2 folds), MFDO (22.2 folds, 31.3 folds). The most potent mPT pore-opening fraction (MFDO) enhanced mitochondrial ATPase activity, inhibited Fe-induced lipid peroxidation and caused cytochrome c release. GC-MS analysis of CMDO revealed the presence of bioactive compounds including methyl propanamide, Dibutyl phthalate, saturated and unsaturated fatty acids.
 Conclusion: Methanol fraction (MFDO) of CMDO most potently induced mPT pore opening via enhancement of mitochondrial ATPase activity, which was substantiated by the release of cytochrome c (in vitro). This includes MFDO as a candidate pharmacologic remedy for diseases associated with insufficient apoptosis.

Methanol Fraction of Daniellia oliveri (ROLFE) Leaves Induces Mitochondrial-mediated Apoptosis in Rats via Alteration of Liver Mitochondrial Viability

“…Studies have attributed the antioxidative potential of medicinal plants to the presence of antioxidative phytochemicals such as flavonoids and phenols [32,33]. Since MFDO induced mitochondrial mPT pore opening, enhanced mitochondrial F 1 F 0 ATPase and inhibited mitochondrial lipid peroxidation in vitro [16], the influence of MFDO on antioxidant enzymes and apoptotic biomarkers were investigated.…”

“…Our previous study on the crude methanol extract of the plant revealed the presence of several phytochemicals and also that MFDO leaves is the most potent of all solvent fractions in the induction of mitochondrial permeability transition pore (mPT), enhancement of mitochondrial F 1 F 0 ATPase activity and inhibition of mitochondrial lipid peroxidation in rat liver in vitro [16]. It is in view of this preliminary study that further investigation on the influence of MFDO on antioxidant enzymes and apoptotic biomarkers were carried out on rat liver.…”

Gliclazide and Crassocephalum rubens leaf extract inhibit glucose-induced mitochondrial permeability transition pore (MPTP) opening in isolated pancreas mitochondria of Wistar rats

“…The use of plants as medicine has been well documented over the years, and with availability of modern equipment and means of analyses, the active principles of these plants have been isolated, and their therapeutic potential described, leading to the development of drugs (14). Earlier studies have reported the modulatory effect of plants on MPTP opening, usually triggered by Ca 2+ (15)(16)(17). This modulatory effect is usually ascribed to the presence of health promoting bioactive compounds in the plants.…”