Icariin alleviates the apoptosis of chondrocytes in osteoarthritis through regulating SIRT‐1‐Nrf2‐HO‐1 signaling

淫羊藿苷 活力测定 细胞凋亡 化学 体内 细胞生物学 西妥因1 MTT法 药理学 信号转导 软骨 软骨细胞 分子生物学 体外 生物化学 生物 下调和上调 医学 病理 解剖 生物技术 基因 替代医学
作者
Ying‐song Liu,Haobo Zhong,Wei‐le Liu,Xin‐huan He,Xiao‐rui Zhan,Chunhan Sun
出处
期刊:Chemical Biology & Drug Design [Wiley]
卷期号:103 (4)
标识
DOI:10.1111/cbdd.14518
摘要

Abstract Icariin has shown the potential to treat osteoarthritis (OA), but the specific mechanism still needs further exploration. Therefore, this study attempted to reveal the effect and mechanism of icariin on OA based on in vitro and in vivo experiments. In vivo, a mouse model of OA was established by cutting the anterior cruciate ligament, and 10 mg/kg icariin was given to mice orally. Then, the OA injury and pathological changes of cartilage tissue in mice were identified by OA index and hematoxylin and eosin staining. In vitro, the viability of C28/I2 cells incubated with different concentrations of icariin was detected by 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐ phenytetrazoliumromide assay. Subsequently, C28/I2 cells induced by IL‐1β were used as the cell model of OA, the expression of Sirtuin (SIRT)‐1 in cells was knocked down, and icariin was added for intervention. Next, western blot was used to observe the expression level of sirtuin 1 (SIRT‐1)‐Nrf2‐heme oxygenase 1 (HO‐1) signaling pathway‐related proteins in cells of each group. Besides, cell viability and apoptosis were detected by MTT and apoptosis assay, and DNA damage was observed by comet assay. In vivo experiments, intragastric administration of icariin could effectively reduce the OA index of mice, improve the pathological changes of cartilage tissue, and obviously activated the SIRT‐1‐Nrf2‐HO‐1 signaling pathway. In vitro experiments, icariin did not exhibit toxic effect on C28/I2 cells, but could activate the SIRT‐1‐Nrf2‐HO‐1 signaling pathway, improve the viability, reduce the level of apoptosis and relieve the DNA damage in OA cells; however, these effects were inhibited by si‐ SIRT‐1. Icariin can improve the symptoms of OA by activating the SIRT‐1‐Nrf2‐HO‐1 signaling pathway.
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