Tetrahydroberberine Prevents Ovariectomy-Induced Bone Loss by Inhibiting RANKL-Induced Osteoclastogenesis and Promoting Osteoclast Apoptosis

Postmenopausal osteoporosis (PMOP) arises from the disruption in bone remodeling caused by estrogen deficiency, leading to a heightened susceptibility to osteoporotic fractures in aging women. Tetrahydroberberine (THB) is a chemical compound extracted from <i>Corydalis yanhusuo</i>, a member of the traditional Chinese medicine series "Zhejiang eight taste", possessing a variety of pharmacological functions such as lowering lipids and preventing muscle atrophy. However, the impact of THB on PMOP has not been systematically explored. In vitro experiments supported that THB suppresses osteoclast formation and resorption of bone concentration-dependently. Further experiments confirmed that these inhibitory effects of THB were related to inhibition on expressions of osteoclast-specific genes, the mitogen-activated protein kinase (MAPK) pathway, and the nuclear factor kappa-B (NF-κB) pathway and an increased apoptosis level in mature osteoclasts. Additionally, THB treatment mitigated the ovariectomy-induced bone loss and improved the skeletal microarchitecture in vivo. In conclusion, THB has such potential to improve the PMOP status.