Wang Yi-Fei, Chang Yue-Yue, Zhang Xue-Meng, Gao Meng-Ting, Zhang Qiu-Lan, Li Xin, Zhang Li, Yao Wei-Feng
School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu 210023, China.
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.
Phytomedicine. 2022 May;99:154020. doi: 10.1016/j.phymed.2022.154020. Epub 2022 Feb 27.
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.
This study aimed to investigate the pharmacological effect and molecular mechanisms of SAL on OP.
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.
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.
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.
骨质疏松症（OP）的特征为骨量低、骨微结构破坏和骨脆性增加。氧化应激增加会导致骨形成与骨吸收平衡失调，进而引发OP。核因子E2相关因子2（Nrf2）是一种参与氧化应激的转录因子，最近有报道称其可调节OP的发生。红景天苷（SAL）具有抗氧化、抗衰老和保护骨骼的功效，是传统中药女贞子的活性成分之一。然而，很少有研究从氧化应激干预的角度探讨SAL预防OP发生发展的潜在机制。
本研究旨在探讨SAL对OP的药理作用及分子机制。
应用叔丁基过氧化氢（t-BHP）诱导的氧化应激模型在体外研究SAL的作用，采用去卵巢（OVX）模型在体内研究SAL对OP的作用。在大鼠成骨细胞（ROBs）和OVX大鼠中探索SAL相关的药效学作用和分子机制。进行网络生物学和细胞代谢组学研究以进一步探究潜在生物标志物、靶点和通路之间的相关性和关联性。
SAL降低了活性氧（ROS）水平和脂质过氧化（LPO）水平，提高了谷胱甘肽过氧化物酶（GPx）和超氧化物歧化酶（SOD）等抗氧化酶的活性，并增强了t-BHP诱导的ROBs和OVX大鼠的成骨分化。机制研究表明，SAL通过上调Nrf2表达并促进其核转位，预防ROBs和OVX大鼠的OP发生发展并减少氧化损伤。网络生物学和细胞代谢组学的联合分析表明，半乳糖代谢和脂肪酸代谢可能是SAL处理后主要受影响的通路。
SAL可通过抑制氧化应激、上调Nrf2促进成骨以及干预半乳糖代谢和脂肪酸代谢来预防OP。我们的研究表明，SAL可能是一种治疗OP的潜在药物。
