Polydatin in rheumatological diseases: Multitarget mechanisms and therapeutic potential

Rheumatological diseases encompass a wide range of conditions primarily affecting the musculoskeletal system. They represent a significant burden on modern society, affecting millions of people worldwide. These chronic and debilitating conditions require long-term management and a multidisciplinary approach that combines pharmacological interventions with lifestyle modifications for optimal patient outcomes. In this context, diet is emerging as a crucial support in managing rheumatological diseases. Certain dietary patterns and specific nutrients can play a significant role in reducing inflammation, alleviating symptoms, and potentially slowing disease progression. Bioactive compounds, which are found in many plant-based foods and are abundant in the Mediterranean diet, are increasingly being recognized as valuable supports to traditional treatments in arthritis. Among them, polydatin has shown potent antioxidant and anti-inflammatory properties. This review aims to comprehensively examine the therapeutic potential of polydatin in various rheumatological diseases, including rheumatoid arthritis, osteoarthritis, crystal-induced arthritis, spondyloarthritis, and systemic lupus erythematosus. Articles included have been identified using keyword-based searches in multiple scientific databases, including PubMed and Scopus. The review highlights polydatin's multi-targeted mechanisms, including antioxidant activity, modulation of inflammatory pathways, regulation of apoptosis and autophagy, and direct interactions with molecular targets like sirtuin 1 and chemokine receptor type 1. Although clinical studies specifically investigating polydatin in rheumatological conditions are scarce, the translational potential of this compound is supported by randomized controlled trials involving other human inflammatory and pain-related disorders. Polydatin's favorable pharmacokinetic profile, enhanced bioavailability, and diverse biological actions position it as a promising natural compound for managing rheumatological diseases. • Polydatin shows anti-inflammatory and antioxidant effects in arthritis models. • Polydatin modulates multiple pathways: NF-κB, SIRT1, oxidative stress, and NETosis. • Polydatin demonstrates chondroprotective and cartilage-preserving activity. • Polydatin reduces crystal-induced inflammation and leukocyte infiltration. • Polydatin shows potential as a natural adjuvant therapy in rheumatic diseases.