The NLRP3 inflammasome in osteoarthritis: a systematic review of traditional, complementary, and integrative medicine efficacy and underlying mechanisms.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint condition mostly affecting the knees characterized by cartilage degradation, synovial inflammation, and chronic pain, with limited effective treatments with minimal side effects. Traditional, complementary, and integrative medicine (TCIM), such as numerous medicinal plants, acupuncture, and folk herbalism, among others, have been historically used to treat symptoms associated with OA, which include joint pain, stiffness, and inflammation. Several herbs and their bioactive constituents have shown potential to modulate key inflammatory pathways like the NLRP3 inflammasome, which is an important regulator of innate immune responses in OA pathophysiology. OBJECTIVE: This review aims to investigate the underlying mechanisms and potential of TCIM to alleviate OA-related pain by modulating the NLRP3 inflammasome. METHODS: A comprehensive literature search across multiple databases, including PubMed, Cochrane Library, Embase, Google Scholar, Scopus, and Web of Science by using a set of MESH and relevant keywords like "NLRP3", "TCIM", "OA", and "Animal" for articles published from January 2000 to August 2024. RESULTS: Twenty-two in vivo studies met the inclusion criteria for the systematic review, and 21 studies for the meta-analysis. Across these studies, TCIM interventions consistently reduced NLRP3, IL-1β, IL-18, and Caspase-1 expression compared with OA controls. Pooled effects were consistently moderate-to-large across all molecular, with low between-study heterogeneity (I² ≈ 0%). Subgroup analyses by OA model, intervention type, and species indicated broadly similar directions of effect. CONCLUSION: TCIM shows potential therapeutic approaches for managing OA-related pain by targeting the NLRP3 inflammasome in preclinical OA models. Further research should investigate the clinical translation of these findings to address the unmet need for effective analgesics in OA.