2. Academic Validation
  3. Oroxylin A reduces osteoclast formation and bone resorption via suppressing RANKL-induced ROS and NFATc1 activation

Oroxylin A reduces osteoclast formation and bone resorption via suppressing RANKL-induced ROS and NFATc1 activation

  • Biochem Pharmacol. 2021 Nov;193:114761. doi: 10.1016/j.bcp.2021.114761.
Yansi Xian 1,  Yuangang Su 2,  Jiamin Liang 2,  Feng Long 1,  Xiaoliang Feng 1,  Yu Xiao 3,  Haoyu Lian 2,  Jiake Xu 4,  Jinmin Zhao 5,  Qian Liu 6,  Fangming Song 7
Affiliations

Affiliations

  • 1 Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, Guangxi, China.
  • 2 Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China.
  • 3 Medical College of Guangxi University, Nanning, Guangxi, China.
  • 4 School of Biomedical Sciences, the University of Western Australia, Perth, Australia.
  • 5 Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China; Orthopaedic Department, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China.
  • 6 Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China. Electronic address: liuqian@gxmu.edu.cn.
  • 7 Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, Guangxi, China. Electronic address: songfangming@gxmu.edu.cn.
PMID: 34492273 DOI: 10.1016/j.bcp.2021.114761
Abstract

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 anti-inflammatory 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 RANKL-induced 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 osteoclast-mediated osteolytic diseases.

Keywords

NFATc1; Oroxylin A; Osteoclast; ROS.

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