期刊
BIOCHEMICAL PHARMACOLOGY
卷 193, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2021.114761
关键词
Oroxylin A; Osteoclast; ROS; NFATc1
资金
- National Natural Science Foundation of China [82060760, 81960405]
- Natural Science Foundation of Guangxi Province [2017GXNSFBA198061, 2018GXNSFAA050092]
- National Science Foundation for Post-doctoral Scientists of China [2018M633618XB]
- Nanning Qingxiu District Science and Technology Bureau key research and development projects [2020028]
- Guangxi Scholarship Fund of Guangxi Education Department (GED)
- Guangxi Institute of Chinese Medicine
Oroxylin A (OA), a natural flavonoid extracted from the root of Scutellaria baicalensis Georgi, demonstrates inhibitory effects on osteoclast formation and function induced by RANKL through regulating ROS and NFATc1. It exhibits protective effects against bone loss in animal models and in vitro experiments.
Excessive bone erosion by osteoclasts is associated with osteoporosis, rheumatoid arthritis, and periprosthetic osteolysis. Targeting osteoclasts may serve as an effective treatment for osteolytic diseases. Although drugs are currently available for the treatment of these diseases, exploring potential anti-osteoclast natural compounds with safe and effective treatment remains needed. Oroxylin A (OA), a natural flavonoid isolated from the root of Scutellaria baicalensis Georgi, has numerous beneficial pharmacological characteristics, including antiinflammatory and antioxidant activity. However, its effects and mechanisms on osteoclast formation and bone resorption have not yet been clarified. Our research showed that OA attenuated the formation and function of osteoclast induced by RANKL in a time-and concentration-dependent manner without any cytotoxicity. Mechanistically, OA suppressed intracellular reactive oxygen species (ROS) levels through the Nrf2-mediated antioxidant response. Moreover, OA inhibited the activity of NFATc1, the master transcriptional regulator of RANKLinduced osteoclastogenesis. OA exhibited protective effects in mouse models of post-ovariectomy (OVX)-and lipopolysaccharide (LPS)-induced bone loss, in accordance with its in vitro anti-osteoclastogenic effect. Collectively, our findings highlight the potential of OA as a pharmacological agent for the prevention of osteoclastmediated osteolytic diseases.
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