Phytochemical Interventions from <i>Withania somnifera</i>: An Approach to Inhibit mPGES-1 and Proteins Involved in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is aninflammatory disorder, with treatments, particularly cyclooxygenase (COX) inhibitors linked to cardiovascular complications. This study explores Withania somnifera (WS) as potential alternative by targeting microsomal prostaglandin E synthase-1 (mPGES-1). In silico analysis revealed binding affinity of WS phytochemical Withanolide D (−9.8 kcal mol−1) with mPGES-1, and has drug-like properties. Five key targets (STAT1, MIF, MMP12, PAD4, and CDK6) were identified, with strong binding to STAT1 (−10.2 kcal mol−1). In vitro validation using WS roots extract in SW982 cells revealed targeting of NFκB pathway, mPGES-1 and the five genes. Results suggest WS and Withanolide D as alternatives to COX inhibitors.