Acute oral toxicity studies of methanolic extract and chloroform fraction of methanolic extract of seeds of Annona muricata

Background: Natural products are considered to be safe and efficacious. Adequate proof of the safety of these herbal drugs is lacking. Objectives: The present study was undertaken to evaluate the acute oral toxicity of methanolic extract of seeds of Annona muricata (MAM) and chloroform fraction of MAM and to derive the lethal dose 50 (LD50) of chloroform fraction of methanol extract of seeds of A. muricata (CMAM). Materials and Methods: Acute toxicity studies of MAM and CMAM were conducted as per the Organisation for Economic Co-operation and Development (OECD) guidelines 420. LD50 of CMAM in rats and mice was estimated as per OECD guidelines 425. The toxic response was evaluated in vitro using hemolytic assay in rat and human erythrocytes. Results: The acute toxicity study done using OECD 420 guideline revealed that MAM and CMAM were safe at 300 mg/kg and produced mortality at 2000 and 5000 mg/kg. On gross examination, congestion of cranial, mesenteric, and uterine blood vessels was observed. As per OECD guidelines 425, CMAM was safe up to 980 mg/kg in rats and up to 175 mg/kg in mice and LD50 value was estimated to be 1310 mg/kg in rats and 310 mg/kg in mice. In vitro hemolytic assay showed that the plant fraction produced hemolysis. Conclusion: The present study concluded the toxicity produced by A. muricata seeds in the vascular system might be due to oxidative injury caused by the phytochemical constituents and it is essential to derive the safe pharmacological dose whenever the plant material is tested for efficacy studies.