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甜菊糖苷通过靶向NF-κB和MAPK信号通路抑制软骨细胞炎症和凋亡,从而在体内改善骨关节炎。

Stevioside targets the NF-κB and MAPK pathways for inhibiting inflammation and apoptosis of chondrocytes and ameliorates osteoarthritis in vivo.

作者信息

Cai Tingwen, Ye Hantao, Jiang Hongyi, Lin Chihao, Lou Chao, Wang Weidan, Yan Zijian, Xue Xinghe, Pan Xiaoyun, Lin Jian

机构信息

Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

出版信息

Int Immunopharmacol. 2023 Feb;115:109683. doi: 10.1016/j.intimp.2023.109683. Epub 2023 Jan 9.

DOI:10.1016/j.intimp.2023.109683
PMID:36630751
Abstract

Osteoarthritis (OA) is a joint disease that is characterized by articular cartilage degeneration and destruction. Stevioside (SVS) is a diterpenoid glycoside extracted from Stevia rebaudiana Bertoni with some specific effects against inflammatory and apoptotic, whereas it is still unclear what function SVS has in osteoarthritis. This study focuses on the anti-inflammatory and anti-apoptosis functions of SVS on chondrocytes induced by interleukin (IL)-1beta, and the role of SVS in an osteoarthritis model for mice. We can detect the production of inflammatory factors such as nitric oxide (NO) and prostaglandin E2 (PGE2) using real-time quantitative polymerase chain reaction (RT-qPCR), the Griess reaction, and enzyme linked immunosorbent assay (ELISA). On the basis of Western blot, we have observed the protein expressions of cartilage matrix metabolism, inflammatory factors, and apoptosis of chondrocytes. Simultaneously, the pharmacological effects of SVS in mice were evaluated by hematoxylin and eosin (HE), toluidine blue, Safranin O, and immunohistochemical staining. The results show that SVS slows extracellular matrix degradation and chondrocyte apoptosis. In addition, SVS mediates its cellular effect by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. Meanwhile, molecular docking studies revealed that SVS has excellent binding capabilities to p65, extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). The study suggests that SVS can be developed as a potential osteoarthritis treatment.

摘要

骨关节炎(OA)是一种以关节软骨退变和破坏为特征的关节疾病。甜菊糖苷(SVS)是从甜叶菊中提取的一种二萜糖苷,具有一定的抗炎和抗凋亡作用,但其在骨关节炎中的作用尚不清楚。本研究聚焦于SVS对白细胞介素(IL)-1β诱导的软骨细胞的抗炎和抗凋亡功能,以及SVS在小鼠骨关节炎模型中的作用。我们可以使用实时定量聚合酶链反应(RT-qPCR)、格里斯反应和酶联免疫吸附测定(ELISA)来检测一氧化氮(NO)和前列腺素E2(PGE2)等炎症因子的产生。基于蛋白质印迹法,我们观察了软骨细胞的软骨基质代谢、炎症因子和凋亡相关蛋白的表达。同时,通过苏木精和伊红(HE)染色、甲苯胺蓝染色、番红O染色和免疫组织化学染色评估SVS在小鼠体内的药理作用。结果表明,SVS减缓了细胞外基质降解和软骨细胞凋亡。此外,SVS通过抑制丝裂原活化蛋白激酶(MAPK)和核因子κB(NF-κB)信号通路的激活来介导其细胞效应。同时,分子对接研究表明,SVS对p65、细胞外信号调节激酶(ERK)、p38和c-Jun氨基末端激酶(JNK)具有良好的结合能力。该研究表明,SVS有望开发成为一种治疗骨关节炎的药物。

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