Luteolin in osteoarticular diseases: a review of preclinical studies and translational perspectives.

Osteoarticular diseases, including degenerative, inflammatory, genetic, and metabolic subtypes, cause severe physical impairment, psychological distress, and substantial economic burden globally. Current therapies often fail to halt progression or carry significant side effects, highlighting the need for novel interventions. Luteolin, a natural flavonoid with a C6-C3-C6 skeleton and characteristic hydroxyl substitutions, exhibits diverse pharmacological activities, including antioxidant, anti-inflammatory, and anti-apoptotic effects. It modulates key signaling pathways (e.g., NF-κB, MAPK, Nrf2/ARE, PI3K/Akt) to suppress synovial inflammation, inhibit matrix metalloproteinase-driven cartilage degradation, protect chondrocytes from oxidative stress-induced apoptosis, and regulate immune-metabolic dysfunctions. Preclinical studies demonstrate its potential efficacy in major osteoarticular diseases such as osteoarthritis, rheumatoid arthritis, reheumatic arthritis, gouty arthritis, and traumatic arthritis, with therapeutic effects observed in cell and animal models but not yet validated in human subjects. However, translational challenges persist, including low oral bioavailability, poor aqueous solubility, and a severe lack of large-scale, well-designed clinical validation. Future research should focus on advanced delivery systems, rigorous clinical trials, and exploring understudied mechanisms to facilitate its clinical translation. This review summarizes luteolin's therapeutic potential and mechanisms in osteoarticular diseases, providing critical insights for developing natural therapeutics.