Fractions of Ageratum conyzoides L. (Compositae) induce mitochondrial-mediated apoptosis in rats: Possible option in monosodium glutamate-induced hepatic and uterine pathological disorder

Abstract

Ethnopharmacological relevanceSeveral pathological disorders have been attributed to either oxidative stress or defect in apoptotic signaling pathway. Some bioactive compounds elicit their antiproliferative properties by induction of apoptosis via mitochondrial permeability transition (mPT) pore opening. Aim of studyThe present study therefore investigated the effects of various fractions of methanol extract of Ageratum conyzoides L. (MEAC) on mitochondrial-mediated apoptosis and the possible protective potential of the most potent against monosodium glutamate (MSG)-induced hepatic damage and uterine pathological disorder. The plant is folklorically used in the treatment of cancer and gynecological disorder. Materials and methodsThe MEAC was partitioned in succession and concentrated at 40 °C to obtain chloroform(CFAC), ethylacetate(EFAC) and methanol(MFAC) fractions. Mitochondria were isolated by differential centrifugation. The opening of mPT pore, mATPase activity and hepatic DNA fragmentation were assessed spectrophotometrically. Caspases 9 and 3, SOD and GSH-Px activities and MDA level were determined using ELISA technique. Histological assessment of the liver and uterine sections and GC-MS analysis of the most potent fraction were carried out. ResultsThe investigation showed that oral administration of the fractions caused induction of mPT pore opening, enhanced mATPase activity, upregulated the activities of caspases 9 and 3 and also, caused hepatic DNA fragmentation with CFAC being the most potent. The CFAC reversed severe MSG-induced hepatic damage and uterine hyperplasia. The MSG-induced oxidative stress was normalized by CFAC. The GC-MS analysis of CFAC revealed the presence of some pharmacologically relevant phytochemicals. ConclusionThese findings therefore suggest that fractions of Ageratum conyzoides induce mitochondrial-mediated apoptosis. Moreover, CFAC, which is the most potent has a promising antioxidant and antiproliferative potential against MSG-induced hepatic and uterine pathological disorder.