Withanolides as Prospective Drug Candidates: Production and Therapeutic Applications-A Review

Withanolides are a group of steroidal lactones predominantly present in the genus 'Withania'. These compounds exhibit cytotoxic, neurological, immunomodulatory, and anti-inflammatory activities. Structural diversity leads to various kinds of withanolides with different biological functionality. There is an increasing market demand for withanolides as they exhibit great therapeutic potential and can be explored for developing novel drug entities. Withanolides are primarily produced from plants that are more prone to diseases and are on the verge of endangerment. From the plant sources, the yield of withanolides is meagre (0.5 - 2%), which cannot meet the market demand, and the production cost is very high. This leads to the exploration of an alternative sustainable source for withanolide production. Endophytic fungi can produce host plant metabolites and can be investigated as an alternative source for withanolides production. Endophytic fungi can be isolated from the host plant species producing withanolides and cultured further for production. Studying the genes of the withanolides' biosynthetic pathway (their upregulation or downregulation), media optimisation, co-culture, and various elicitors may enhance withanolides production. In silico approaches like molecular docking and quantitative structure-activity relationship studies may also aid in understanding the mechanism of action of withanolides on a specific target to cure a disease. Nanotechnology techniques help in designing the formulation of withanolides so that they can cross the blood-brain barrier and improve therapeutic effectiveness. This article highlights the biochemistry, biosynthetic pathway, mode of action, therapeutic potential of withanolides, and exploration of endophytic fungi as an alternative source to produce withanolides cost-effectively.