Preclinical Safety Evaluation of Vernolac, a Commercially Available Polyherbal Nutraceutical Comprising Vernonia zeylanica, Nigella sativa, Hemidesmus indica, Smilax glabra, and Leucas zeylanica, in Wistar Rats

Abstract Vernolac is a commercially available polyherbal formulation comprising Vernonia zeylanica aerial parts, Nigella sativa s eeds, Hemidesmus indica roots, Smilax glabra rhizome, and Leucas zeylanica aerial parts. Although previous in vitro studies have demonstrated anticancer potential of Vernolac and its active ingredients, safety data are available only for some of the plant ingredients of Vernolac. In the present study, acute and 28-day repeat-dose toxicity of Vernolac were evaluated in Wistar rats following OECD guidelines 420 and 407, respectively. Acute toxic effect was investigated during 14 days after administering a single oral dose of 2000 mg/kg to 10 animals (5 males, 5 female) which was followed by repeat-dose study where a human equivalent therapeutic dose HED (165 mg/kg/day), a mid-dose (2x HED, 330mg/kg/day) and a high dose (4x HED, 660 mg/kg/day) were administered separately to a group of 10 fresh animals (5 male, 5 female) for 28 days. In both acute and repeat-dose studies, no morbidity, mortality, changes in food and water intake, relative organ weights, microscopic changes in organs, hematological changes, or clinical signs of toxicity were observed. In the acute study, significant differences appeared only in AST and ALT levels in males, indicating the liver may be a target organ of toxicity at extremely high doses. In 28-days repeated dose study, a significant reduction in ALT was observed only in females receiving high doses, with no changes in males. In summary, a dose up to four times the therapeutic daily dose is non-toxic in Wistar rats over a 28-day period.