Antimalarial properties and preventive effects on mitochondrial dysfunction by extract and fractions of Phyllanthus amarus (Schum. and Thonn) in Plasmodium berghei-infected mice

Abstract

Abstract Objectives Broad spectrum antimalarial drugs without deleterious effects on mitochondria are scarce. It is in this regard that we investigated the potency of methanol extract and solvent fractions of Phyllanthus amarus on chloroquine-susceptible and resistant strains of Plasmodium berghei, toxicity and its consequential effects on mitochondrial permeability transition (mPT) pore opening. Methods Malaria was induced in male Swiss mice with susceptible (NK 65) strain, divided into groups (n=5) and treated with 100, 200 and 400 mg/kg of methanol extract, n-hexane, dichloromethane, ethylacetate and methanol fractions daily for seven days. Percentage parasitemia and parasite clearance were determined microscopically. The two most potent fractions were tested on resistant (ANKA) strains. Heme and hemozoin contents were determined spectrophotometrically. The mPT, mitochondrial ATPase (mATPase) and lipid peroxidation (mLPO) were determined spectrophotometrically. Similar groups of animals were used for toxicity studies. Results Dichloromethane fraction (400 mg/kg) had the highest antimalarial curative effect via least parasitemia (0.49) and high clearance (96.63) compared with the negative control (10.08, 0.00, respectively), had the highest heme and least hemozoin contents (16.23; 0.03) compared with the negative control (8.2, 0.126, respectively). Malaria infection opened the mPT, caused significant increase in mLPO and enhanced mATPase; while dichloromethane fraction reversed these conditions. Serum ALT, AST, ALP, GGT, urea and creatinine of dichloromethane fraction-treated mice decreased relative to control. No significant lesion was noticed in liver and kidney tissue sections. Conclusions Dichloromethane fraction of Phyllanthus amarus had the highest antimalarial activity with the highest mito-protective effect and it was well tolerated without toxic effects.