A comprehensive review on Phyto-MAP: A novel approach of drug discovery against Mycobacterium avium subspecies paratuberculosis using AYUSH heritage

Ethnopharmacological relevance: Indian system of Traditional medicine, AYUSH (Ayurveda, Yoga, Unani, Siddha, and Homeopathy) has great potential with a History of Safe Use (HOSU) of thousands of medicinal plants included in pharmacopoeias. The multi-targeted approach of phytoconstituents present in different traditionally used medicinal plants makes them suitable candidates for research against various infective pathogens. MAP which is a dairy-borne pathogen is associated with the development of Johne's disease in ruminants and Crohn's disease like autoimmune disorders in human beings. There are no reliable treatment alternatives available against MAP, leaving surgical removal of intestines as the sole option. Hence, there exists an urgent need to search for leads against such infection. Aim of the study: The present review has been conducted to find out the ethnopharmacological evidence about the potential of phytoconstituents against Mycobacterium avium subspecies paratuberculosis (MAP), along with the proposal of a potential phyto-MAP mechanism for the very first time taking anti-inflammatory, immunomodulatory, and anti-microbial traditional claims into consideration. Materials and Methods: We have analyzed and reviewed different volumes of the two main traditional scriptures of India i.e. Ayurvedic Pharmacopoeia of India (API) and Unani Pharmacopoeia of India (UPI), respectively-for identification of potential anti-MAP plants based on their claims for related disorders. These plants were further investigated systematically for their scientific publications of the last 20 years (2002-2022) available through electronic databases including Google Scholar, Pubmed, and Scopus. The studies conducted in vitro, cell lines, and in vivo levels were taken into consideration along with the associated mechanisms of phytoconstituents. Results: A total of 70 potential medicinal plants have been identified. Based on the ethnopharmacology, a potential phyto-paratuberculosis (Phyto-paraTB) mechanism has been proposed and out of 70, seven potential antiMAP plants have been identified to have a great future as anti-MAP. Conclusion: A novel and scientifically viable plan has been proposed for addressing anti-MAP plants for stimulating research against MAP and related disorders using mass-trusted AYUSH medicine, which can be used as an alternative remedy in resistance cases otherwise can be advocated as an adjuvant with modern treatments for better management of the disease.