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 A₂ (PLA₂) activity of the Naja naja venom by the ERE. ERE showed significant inhibition of PLA₂ 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 A₂ inhibition potential, which was confirmed by molecular docking studies with PLA₂. 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 PLA₂ activity among other venom-derived factors.