Oroxin B Attenuates Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Formation and Activity

• Published in: Drug design, development and therapy development and therapy, 2021-01, Vol.15, p.4811-4825
• Main Authors: Huang, Jun-Ming, Wang, Chen-Zhong, Lu, Shun-Yi, Wang, Zhe, Yan, Zuo-Qin
• Format: Article
• Language: English
• Subjects: Animals; Anticancer properties; Antitumor activity; Attenuation; Biomedical materials; Bone growth; Bone loss; Bone marrow; Bone resorption; Bone Resorption - drug therapy; c-Fos protein; Cancer; Cathepsin K; Cathepsins; Cells, Cultured; Cytokines; Disaccharides - pharmacology; Estrogens; Flavones - pharmacology; Flavonoids; Fractures; Gelatinase B; Herbal medicine; Hormone replacement therapy; Kinases; Macrophages; Male; MAP kinase; mapk; Medicine, Botanic; Medicine, Chinese; Medicine, Herbal; Mice; Mice, Inbred C57BL; nf-κb; NF-κB protein; Original Research; oroxin b; osteoclast; Osteoclastogenesis; Osteoclasts; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteogenesis - drug effects; Osteoporosis; Ovariectomy; Phosphatase; Phosphorylation; rankl; TRANCE protein; Transcription factors
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S328238

Osteoclasts are the major players in bone resorption and have always been studied in the prevention and treatment of osteoporosis. Previous studies have confirmed that a variety of flavonoids inhibit osteoporosis and improve bone health mainly through inhibiting osteoclastogenesis. Oroxin B (OB) is a flavonoid compound extracted from traditional Chinese herbal medicine (L.) Vent, exerts potent antitumor and anti-inflammation effect, but its effect on osteoclastogensis remains unknown. We comprehensively evaluated the effect of OB on the formation and function of osteoclasts and the underling mechanism by bone marrow-derived macrophage in vitro. In vivo, we used mice ovariectomized model to verify the protective effect of OB. OB was found to inhibit osteoclast formation and bone resorption function in vitro, in a dose-dependent manner and the increased osteoclastic-related genes induced by RANKL (NFATc1, c-fos, cathepsin K, RANK, MMP9 and TRAP) were also attenuated following OB treatment. Mechanistical investigation showed OB abrogated the increased phosphorylation level of MAPK and NF-κB pathway, and diminished the expression of the vital transcription factors for osteoclastogenesis. OB also prevented ovariectomy (OVX)-induced bone loss by inhibiting osteoclast formation and activity in mice. Our study demonstrated that OB may act as an anti-osteoporosis agent by inhibiting osteoclast maturation and attenuating bone resorption.