Feng Yanling, Tang Xulei
Department of Endocrinology and Metabolism, The Second Hospital of Lanzhou University, Lanzhou 730030, China.
Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou 730000, China.
J Pharm Pharmacol. 2024 Jul 5;76(7):813-823. doi: 10.1093/jpp/rgae033.
Elevated reactive oxygen species levels promote excessive osteoclastogenesis and bone resorption. Puerarin, a natural antioxidant, can prevent bone loss through its antioxidant effects; however, the underlying molecular mechanism remains unclear. This study aimed to explore the effects of puerarin on osteoclast differentiation and bone resorption by regulating the PI3K/AKT/FoxO1 signaling pathway.
An ovariectomized (OVX) rat model of osteoporosis and H2O2-induced oxidative cell model of RAW 264.7 cells were established. The following indices were measured including bone μ-CT scanning and the protein expression levels of FoxO1, p-FoxO1, and catalase were detected using western blotting.
Puerarin strongly alleviated oxidative stress-induced bone loss in OVX rats in vivo owing to its antioxidant effects. Puerarin improved the oxidative stress status of cells and inhibited osteoclast formation in vitro. Moreover, the protein expression of FoxO1 and its downstream target, catalase, was upregulated by puerarin.
Puerarin improved the OPG/RANKL ratio, upregulated the protein expression and transcriptional activity of FoxO1, and suppressed the differentiation of RAW264.7 cells into osteoclasts. FoxO1 is a pivotal target of puerarin to confer anti-osteoporosis effects.
活性氧水平升高会促进破骨细胞过度生成和骨吸收。葛根素是一种天然抗氧化剂，可通过其抗氧化作用预防骨质流失；然而，其潜在的分子机制仍不清楚。本研究旨在通过调节PI3K/AKT/FoxO1信号通路来探讨葛根素对破骨细胞分化和骨吸收的影响。
建立去卵巢（OVX）大鼠骨质疏松模型和H2O2诱导的RAW 264.7细胞氧化应激细胞模型。测量以下指标，包括骨μ-CT扫描，并使用蛋白质印迹法检测FoxO1、p-FoxO1和过氧化氢酶的蛋白表达水平。
葛根素因其抗氧化作用在体内显著减轻了氧化应激诱导的OVX大鼠骨质流失。葛根素改善了细胞的氧化应激状态，并在体外抑制了破骨细胞的形成。此外，葛根素上调了FoxO1及其下游靶点过氧化氢酶的蛋白表达。
葛根素提高了OPG/RANKL比值，上调了FoxO1的蛋白表达和转录活性，并抑制了RAW264.7细胞向破骨细胞的分化。FoxO1是葛根素发挥抗骨质疏松作用的关键靶点。
