ABSTRACT
Osteoporosis is the result of osteoclast formation exceeding osteoblast production, and current osteoporosis treatments targeting excessive osteoclast bone resorption have serious adverse effects. There is a need to fully understand the mechanisms of osteoclast-mediated bone resorption, identify new drug targets, and find better drugs to treat osteoporosis. Gar C (Gar C) is a major naturally occurring phytochemical isolated from mangosteen, and is a derivative of the naturally occurring phenolic antioxidant lutein. We used an OP mouse model established by ovariectomy (OVX). We found that treatment with Gar C significantly increased bone mineral density and significantly decreased the expression of TRAP, NFATC1 and CTSK relative to untreated OP mice. We found that Garcinone C could disrupt osteoclast activation and resorption functions by inhibiting RANKL-induced osteoclast differentiation as well as inhibiting the formation of multinucleated osteoclasts. Immunoblotting showed that Gar C downregulated the expression of osteoclast-related proteins. In addition, Gar C significantly inhibited RANKL-induced ROS production and affected NF-κB activity by inhibiting phosphorylation Formylation of P65 and phosphorylation and degradation of ikba. These data suggest that Gar C significantly reduced OVX-induced osteoporosis by inhibiting osteoclastogenesis and oxidative stress in bone tissue. Mechanistically, this effect was associated with inhibition of the ROS-mediated NF-κB pathway.
ABSTRACT
CONTEXT: With the development of society, the number of patients with osteoporosis is increasing. The prevention and control of osteoporosis has become a serious and urgent issue. With the continuous progress of biomedical research, ferroptosis has attracted increased attention. However, the pathophysiology and mechanisms of ferroptosis and osteoporosis still need further study. Natural products are widely used in East Asian countries for osteoporosis prevention and treatment. OBJECTIVE: In this paper, we will discuss the basic mechanisms of ferroptosis, the relationship between ferroptosis and osteoclasts and osteoblasts, and in vitro and in vivo studies of natural products to prevent osteoporosis by interfering with ferroptosis. METHODS: This article takes ferroptosis, natural products, osteoporosis, osteoblasts and osteoclast as key words. Retrieve literature from 2012 to 2023 indexed in databases such as PubMed Central, PubMed, Web of Science, Scopus and ISI. RESULTS: Ferroptosis has many regulatory mechanisms, including the system XC -/GSH/GPX4, p62/Keap1/Nrf2, FSP1/NAD (P) H/CoQ10, P53/SAT1/ALOX15 axes etc. Interestingly, we found that natural products, such as Artemisinin, Biochanin A and Quercetin, can play a role in treating osteoporosis by promoting ferroptosis of osteoclast and inhibiting ferroptosis of osteoblasts. CONCLUSIONS: Natural products have great potential to regulate OBs and OCs by mediating ferroptosis to prevent and treat osteoporosis, and it is worthwhile to explore and discover more natural products that can prevent and treat osteoporosis.