Anemoside B4 attenuates RANKL-induced osteoclastogenesis by upregulating Nrf2 and dampens ovariectomy-induced bone loss

Zhen Cao; Xuben Niu; Maihuan Wang; Siwang Yu; Mingkun Wang; Silong Mu; Chuan Liu; Yaxi Wang

doi:10.1016/j.biopha.2023.115454

Anemoside B4 attenuates RANKL-induced osteoclastogenesis by upregulating Nrf2 and dampens ovariectomy-induced bone loss

Biomed Pharmacother. 2023 Nov:167:115454. doi: 10.1016/j.biopha.2023.115454. Epub 2023 Sep 8.

Authors

Zhen Cao¹, Xuben Niu², Maihuan Wang³, Siwang Yu⁴, Mingkun Wang⁵, Silong Mu³, Chuan Liu⁶, Yaxi Wang⁷

Affiliations

¹ Department of General Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou 511442, China.
² Department of General Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou 511442, China.
³ Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.
⁴ Department of Molecular and Cellular Pharmacology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
⁵ Department of General Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China.
⁶ Department of Orthopedic, The Seventh Medical Centre, Chinese PLA General Hospital, Beijing 100700, China. Electronic address: liuchuan@301hospital.com.cn.
⁷ Department of Emergency, The Seventh Medical Centre, Chinese PLA General Hospital, Beijing 100700, China. Electronic address: wangyaxi@301hospital.com.cn.

PMID: 37688987
DOI: 10.1016/j.biopha.2023.115454

Abstract

Increased numbers and functional overactivity of osteoclasts are the pathological basis for bone loss diseases such as osteoporosis, which are characterized by cortical bone thinning, decreased trabecular bone quantity, and reduced bone mineral density. Effective inhibition of osteoclast formation and bone resorption are important means of treating such skeletal diseases. Anemoside B4 (AB4), the main active component of Pulsatilla chinensis, possesses a wide range of anti-inflammatory and immunoregulatory effects. However, its effect and mechanism in osteoclast differentiation remain unclear. In this study, we found through tartrate-resistant acidic phosphatase (TRAcP) staining and immunofluorescence staining that AB4 inhibited the differentiation, fusion, and bone-resorption functions of osteoclasts induced by receptor activator of nuclear factor κB ligand (RANKL) in vitro. Additionally, real time PCR (RT-qPCR) and western blot analysis showed AB4 downregulated the expression of osteoclast marker genes, including Nfatc1, Fos, and Ctsk, while upregulating Nrf2 expression. AB4 (5 mg/kg) alleviated bone loss in ovariectomized mice by inhibiting osteoclast formation. Furthermore, the knockout of Nrf2 weakened the inhibitory effects of AB4 on osteoclast formation and related gene expression. In summary, the results suggest AB4 can inhibit osteoclast differentiation and function by activating Nrf2 and indicate AB4 may be a candidate drug for osteoporosis.

Keywords: Anemoside B4; Bone resorption; Nrf2; Osteoclastogenesis; Osteoporosis.