1.Role of Ferroptosis in Osteoarthritis and Traditional Chinese Medicine Intervention: A Review
Xiaojing GUO ; Huan QIN ; Dongliang XIANG ; Yan WANG ; Li ZHANG ; Bo ZHANG ; Shujin WANG ; Xiaotong LI ; Mingyue ZHAO ; Shanhong WU ; Fei PEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):263-272
Osteoarthritis (OA) is characterized by articular cartilage degeneration, synovial hyperplasia, hyperosteogeny, and narrowing of joint space, which can be caused by trauma, inflammation, and other factors. With the increasing global population aging, the incidence of OA is rising year by year, making it a major public health problem that urgently needs to be addressed. Exploring effective treatment schemes is particularly important. The pathogenesis of OA is complex, including oxidative stress, autophagy, and apoptosis. Recent studies have found that ferroptosis, a new type of cell death, is also an important pathogenic factor in OA, characterized by a series of complex changes such as iron ion accumulation, glutathione (GSH) depletion, and mitochondrial dysfunction. Research shows that inhibiting ferroptosis in chondrocytes can promote chondrocyte proliferation, delay extracellular matrix (ECM) degradation, and reduce synovial hyperplasia and inflammation. Targeting ferroptosis is a new direction in the treatment of OA. OA treatment includes intra-articular injections of steroids or hyaluronic acid and artificial joint replacement, but there are limitations. Traditional Chinese medicine (TCM) has been widely used in the treatment of various diseases because of its low cost, low drug resistance, and few side effects. Cell and animal experiments have further confirmed that TCM can intervene in the treatment of OA with ferroptosis from multiple targets, multiple levels, and aspects, but the mechanism of its treatment of OA based on ferroptosis has not been clarified. This paper discussed iron metabolism, lipid peroxidation, cysteine/glutamate transporter system Xc- (system Xc-)/GSH/glutathione peroxidase 4 (GPX4) pathway, nicotinamide adenine dinucleotide phosphate(NADPH)/ferroptosis suppressor protein 1 (FSP1)/coenzyme Q10 (CoQ10) pathway, tumor protein p53 in OA, and related molecular targets of Chinese medicine monomers and compounds on ferroptosis inhibition. Their potential therapeutic mechanisms were further analyzed to provide theoretical guidance for the treatment of OA by TCM and useful reference for the research and development of related drugs.