Modulatory effect of methanol extract of Annona muricata stem bark on mitochondrial membrane permeability transition pore in normal rat liver and monosodium glutamate-induced uterine hyperplasia

Abstract

Uterine fibroids are benign tumors that develop in many women of reproductive age. Surgery is the main approach to treatment while other options are also associated with adverse effects. Studies have shown that certain bioactive agents present in medicinal plants elicit their anti-tumor activity by induction of mitochondrial permeability transition (mPT) opening. This research therefore aimed at investigating the effect of methanol extract of Annona muricata (MEAM) on mPT pore opening in normal and monosodium glutamate-induced uterine hyperplasia using female Wistar rats. Mitochondria, isolated from rat liver were exposed to different concentrations (20, 60, 100, 140 and 180μg/mL) of MEAM. The mPT pore opening, cytochrome c release, mitochondrial ATPase (mATPase) activity and the percentage lipid peroxidation were assessed spectrophotometrically. Histological effects of MEAM on the liver, brain and uterus of normal and MSG-treated rats were investigated. The in vitro results showed a significant induction of mPT pore opening by 2.4, 4.2 and 6.4 folds, release of cytochrome c and enhancement of mATPase activity at 100,140 and 180μg/mL, respectively. However, oral administration of MEAM did not induce mPT pore opening, neither any significant release of cytochrome c nor enhancement of mATPase activity at all the dosages used. However, histological assay revealed the presence of MSG-induced cellular damage and uterine hyperplasia which was ameliorated by MEAM co-administration. These findings suggest that MEAM contains phytochemicals that can ameliorate MSG-induced damage and uterine hyperplasia in rats; however, the mechanism might not be via upregulation of mitochondrial-mediated apoptosis.