Research progress on the mechanism of natural products based on mitochondrial endoplasmic reticulum homeostasis in the intervention of knee osteoarthritis
Key Words
knee osteoarthritis;natural products;inflammation;oxidative stress;mitochondria;endoplasmic reticulum
Author Name
Affiliation
JIN Tong
Hubei University of Chinese Medicine, Wuhan 430065, China
Abstract
Knee osteoarthritis（KOA） is one of the most prevalent degenerative joint disorders among the elderly. Its pathological progression is characterized by articular cartilage destruction，synovial inflammation，subchondral bone remodeling，and disruption of the intra-articular microenvironment. Emerging evidence has highlighted the central roles of inflammatory responses，oxidative stress，mitochondrial dysfunction，and dysregulation of mitochondria-associated endoplasmic reticulum membranes（MAMs） in KOA development. Crosstalk among these mechanisms forms a vicious cycle of “inflammation-oxidative stress-energy metabolism imbalance”，accelerating chondrocyte senescence and apoptosis. Natural products-particularly flavonoids，polyphenols，terpenoids，and alkaloids-exert multi-target actions and exhibit strong anti-inflammatory，antioxidant，and mitochondrial-protective effects. Increasing studies show that natural products can modulate NF-κB/MAPK signaling，activate the Nrf2/ARE pathway，restore mitochondrial function，promote mitophagy，and potentially regulate MAMs homeostasis to alleviate KOA. This review provides a systematic summary of the core pathological mechanisms of KOA and elaborates on the molecular mechanisms by which natural products modulate inflammation，oxidative stress，mitochondrial homeostasis，and MAMs function. Future research directions are proposed to support the development of new natural-product-based therapeutics for KOA.
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