Coumarins in musculoskeletal health: a systematic review

Musculoskeletal diseases encompass a spectrum of pathologies such as osteoporosis, rheumatoid arthritis, osteoarthritis, and osteosarcoma, characterized by degenerative alterations and aberrant hyperplasia in bone mass, synovial tissue, and cartilage. Recently, botanical compounds have demonstrated promising potential in ameliorating skeletal and muscular aging. Coumarins, as naturally occurring phytochemicals, exhibit diverse pharmacological properties including anti-inflammatory, antiviral, antioxidant, antitumor, and immunomodulatory activities. This comprehensive review systematically elucidates how coumarins and their derivatives confer protection against Musculoskeletal Diseases primarily through modulation of inflammatory and oxidative mediators. These compounds target pivotal signaling pathways, such as NF-κB, MAPKs, Wnt/β-catenin, Sirt1, and PI3K/AKT, to enhance bone mineral density, mitigate cartilage degradation, suppress synovial pannus formation, and impede sarcoma cell migration. Despite their therapeutic promise, clinical translation of coumarins requires further investigation. Their dual capabilities in regulating bone metabolic homeostasis and immune responses, coupled with epigenetic interactions in musculoskeletal pathophysiology, provide valuable perspectives for retarding disease progression and advancing novel therapeutic interventions.