Neutralization of Naja naja venom induced lethality, edema and myonecrosis by ethanolic root extract of Coix lacryma-jobi

Coix lacryma-jobi, commonly known as job’s tear, is a tall grain-bearing tropical plant of the family Poaceae. The ethanolic root extract (ERE) of the plant was investigated for the first time for anti-venom activity against Indian cobra Naja naja venom. In-vitro studies were conducted to determine neutralization of phospholipase A(2) (PLA(2)) activity of the Naja naja venom by the ERE. ERE showed significant inhibition of PLA(2) activity, which was further confirmed from effective neutralization of human red blood cells (HRBC) lysis induced by the venom. In addition, venom-induced proteolysis, fibrinogenolysis, DNase activity were also neutralized by the ERE, which contained carbohydrates, glycolides, resins and tannins. Oral administration of ERE at doses levels 100, 200 and 400 mg/kg effectively inhibited Naja naja venom-induced lethality in mice. Myotoxicity induced by Naja naja venom, measured by creatine kinase activity in rats was significantly neutralized by the ERE at a dose of 200 mg/kg. Stigmasterol, as one of the component isolated from the ERE, was found to have venom phospholipase A(2) inhibition potential, which was confirmed by molecular docking studies with PLA(2). In summary, these studies indicate the ability of ERE of Coix lacryma-jobi to effectively neutralize the toxic effects of the venom is, in part, contributed by the inhibition of PLA(2) activity among other venom-derived factors.