Therapeutic Adjuvant Potential and Herb-Drug Interaction of Withania somnifera (L.) Dunal (Ashwagandha) co-administered with First-Line Anti-Tubercular Drugs – an In silico Exploration

Abstract Tuberculosis (TB) remains a major global health burden despite the availability of effective drugs and policy interventions. Prolonged treatment duration, the emergence of drug resistance, and adverse effects of anti-tubercular drugs (ATDs) highlight the need for supportive adjuvants. Objective: We performed an in-silico investigation of Withania somnifera (Ashwagandha), a popular rejuvenator herb ( Rasayana ) in Ayurveda with established antioxidant, anti-inflammatory, and immunomodulatory properties for its potential role in TB management. Molecular docking was performed to evaluate interactions of key Ashwagandha phytoconstituents with human drug-metabolizing enzymes and transporters influencing the pharmacokinetics of first-line TB drugs (isoniazid, rifampicin, pyrazinamide, ethambutol), as well as with Mycobacterium tuberculosis proteins essential for bacterial survival and virulence. Several compounds, including 12-Deoxy Withastramonolide, Withanoside IV, Withanolide A, and Withaferin A, exhibited favorable binding to both sets of targets, suggesting possible antimycobacterial activity and beneficial herb–drug interactions. These findings indicate that Ashwagandha may provide dual benefits direct inhibition of the pathogen and enhanced ATD availability supporting its potential as an adjuvant in TB therapy warranting clinical evaluation.