Salidroside protects against osteoporosis in ovariectomized rats by inhibiting oxidative stress and promoting osteogenesis via Nrf2 activation

Yi-Fei Wang; Yue-Yue Chang; Xue-Meng Zhang; Meng-Ting Gao; Qiu-Lan Zhang; Xin Li; Li Zhang; Wei-Feng Yao

doi:10.1016/j.phymed.2022.154020

Salidroside protects against osteoporosis in ovariectomized rats by inhibiting oxidative stress and promoting osteogenesis via Nrf2 activation

Phytomedicine. 2022 May:99:154020. doi: 10.1016/j.phymed.2022.154020. Epub 2022 Feb 27.

Authors

Yi-Fei Wang¹, Yue-Yue Chang¹, Xue-Meng Zhang¹, Meng-Ting Gao¹, Qiu-Lan Zhang¹, Xin Li¹, Li Zhang², Wei-Feng Yao³

Affiliations

¹ School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu 210023, China.
² School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
³ School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: yaowf@njucm.edu.cn.

PMID: 35278902
DOI: 10.1016/j.phymed.2022.154020

Abstract

Background: Osteoporosis (OP) is characterized as low bone mass, bone microarchitecture breakdown and bone fragility. The increase of oxidative stress could lead to breakdown in the balance of bone formation and resorption which gives rise to OP. Nrf2 is a transcription factor which takes part in oxidative stress and recently was reported that it can regulate the occurrence of OP. Salidroside (SAL) with the efficacies of anti-oxidation, anti-aging and bone-protection is one of the active ingredients in Ligustri Lucidi Fructus, a traditional Chinese medicinal herb. Nevertheless, few studies have explored the potential mechanism of SAL preventing OP development from the perspective of oxidative stress intervention.

Purpose: This study aimed to investigate the pharmacological effect and molecular mechanisms of SAL on OP.

Study designs and methods: A tert-butyl hydroperoxide (t-BHP)-induced oxidative stress model was applied for investigating the effects of SAL in vitro, and an ovariectomized (OVX) model was used for in vivo study on the effect of SAL for OP. Related pharmacodynamic actions and molecular mechanisms of SAL were explored in both rat osteoblasts (ROBs) and OVX rats. Network biology and cell metabolomics were performed for further investigating the correlation and association among potential biomarkers, targets and pathways.

Results: SAL reduced levels of ROS and lipid peroxidation (LPO), increased activities of antioxidant enzymes like GPx and SOD, and enhanced osteogenic differentiation in t-BHP-induced ROBs and OVX rats. Mechanistic studies showed SAL prevented OP development and reduced oxidative damage in ROBs and OVX rats through up-regulating Nrf2 expression and facilitating its nuclear translocation. The joint analysis of network biology and cell metabolomics revealed that galactose metabolism and fatty acid metabolism could be the major influenced pathways following treatment with SAL.

Conclusion: SAL could protect against OP by inhibiting oxidative stress, promoting osteogenesis through the up-regulation of Nrf2 and intervening galactose metabolism and fatty acid metabolism. Our study implied that SAL may be a potential drug to treat OP.

Keywords: Nrf2; Osteoblast; Osteoporosis; Ovariectomized rats; Oxidative stress; Salidroside.