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

Background: Alteration of mitochondrial viability by induction of mitochondrial permeability transition (mPT) brings about mitochondrial-mediated apoptosis. D. oliveri is a medicinal plant traditionally used for the management of certain ailments including tumours. Purpose: Investigating effects of Methanol Fraction of D. oliveri Leaves (MFDO) on mitochondrial-mediated apoptosis. Methods: Twenty-four male rats (70-90 g) were grouped into 4 according to intraperitoneal treatments (14 days): control (distilled water), 50, 100 and 200 mg/kg MFDO. The mitochondrial ATPase and DNA fragmentation were assayed by spectrophotometry. Apoptotic biomarkers were assayed by immunohistochemistry. Caspases-3 and -9 were assessed using ELISA. GC-MS was employed to identify compounds in MFDO. Results : MFDO exhibited in vitro antioxidant properties through inhibition of DPPH and ferric radicals. There was induction of mPT by 50, 100 and 200 mg/kg MFDO relative to control. Furthermore, MFDO inhibited mLPO and enhanced mATPase relative to control. Expression of Bax, p53 and cytochrome c proteins were up-regulated, while Bcl-2 protein expression was down-regulated. Caspase-3 and -9 activities were enhanced, and DNA fragmentation was induced. GC-MS of MFDO revealed the presence of apoptosis-inducing compounds. Conclusion : MFDO induces mitochondrial-mediated apoptosis via alteration of rats liver mitochondrial viability. MFDO is therefore relevant for drug development against diseases.