Toxicity evaluation of a novel anticancer formulation of withania somnifera (L.) Dunal

Abstract

In the present investigation, toxicity profile of a novel bio active formulation from Withania somnifera (WS) has been carried out. WS, a reputed Indian medicinal herb and popularly known as Ashwagandha, is widely acclaimed to possess significant pharmacological activities. Extensive investigations for its bio activities were carried out and reported to validate the acclaimed medicinal uses of this herb in traditional healing systems such as Ayurveda and also in several other folklore traditions in diverse geographical areas. Presently, different parts of WS like roots and leaves in various forms are being used in polyherbal preparations that are available in India and other South East Asian countries. In spite of its abundant use the chemical characterization with respect to its medicinal uses has not been described in such herbal preparations. In recent times considerable efforts have been done in Indian Institute of Integrative Medicine, Jammu to identify a chemically standardized fraction for a defined bio activity. In view of a significant immunomodulatory and anticancer profile of this herb a novel formulation which comprised of chemically identifiable constituents in a blend of roots and leaves of this plant has been identified. This has been designated as WSF which was standardized on the basis of 11 marker withanolides. This WSF was found to possess a significant immunomodulatory and anticancer activity in several pre clinical studies. These studies have suggested a potential use of this formulation for a therapeutic use. Keeping the therapeutic potential of the formulation into consideration, a for the detailed toxicity evaluation has been undertaken in the present investigation. In order to achieve the objective WSF was evaluated for 1) acute toxicity profile and 2) chronic toxicity profile as per OECD guidelines, 3) genotoxicity potential by applying battery of test (chromosome aberration assay, micronucleus assay, DNA damage evaluation by COMET assay, sperm abnormality assay and micronucleus assay