Han Seong Jae, Jun Jimoon, Eyun Seong-Il, Lee Choong-Gu, Jeon Jimin, Pan Cheol-Ho
Department of Biomedical Sciences, Graduate School of Medicine, Ajou University, Suwon 16499, Korea.
Department of Pharmacology, School of Medicine, Ajou University, Suwon 16499, Korea.
Pharmaceuticals (Basel). 2021 Mar 8;14(3):241. doi: 10.3390/ph14030241.
Schisandrol A possesses pharmacological properties and is used to treat various diseases; however, its effects on osteoarthritis (OA) progression remain unclear. Here, we investigated Schisandrol A as a potential therapeutic agent for OA. In vitro, Schisandrol A effects were confirmed based on the levels of expression of catabolic factors (MMPs, ADAMTS5, and Cox2) induced by IL-1β or Schisandrol A treatment in chondrocytes. In vivo, experimental OA in mice was induced using a destabilized medial meniscus (DMM) surgical model or oral gavage of Schisandrol A in a dose-dependent manner, and demonstrated using histological analysis. In vitro and in vivo analyses demonstrated that Schisandrol A inhibition attenuated osteoarthritic cartilage destruction via the regulation of Mmp3, Mmp13, Adamts5, and Cox2 expression. In the NF-κB signaling pathway, Schisandrol A suppressed the degradation of IκB and the phosphorylation of p65 induced by IL-1β. Overall, and Schisandrol A reduced the expression of catabolic factors by blocking NF-κB signaling and prevented cartilage destruction. Therefore, Schisandrol A attenuated OA progression, and can be used to develop novel OA drug therapies.
五味子醇甲具有药理特性,可用于治疗多种疾病;然而,其对骨关节炎(OA)进展的影响仍不清楚。在此,我们研究了五味子醇甲作为OA的一种潜在治疗药物。在体外,基于白细胞介素-1β(IL-1β)或五味子醇甲处理软骨细胞诱导的分解代谢因子(基质金属蛋白酶(MMPs)、含血小板反应蛋白基序的解聚蛋白样金属蛋白酶5(ADAMTS5)和环氧化酶2(Cox2))的表达水平,证实了五味子醇甲的作用。在体内,使用不稳定内侧半月板(DMM)手术模型或按剂量依赖性方式对小鼠口服灌胃五味子醇甲诱导实验性OA,并通过组织学分析进行证实。体外和体内分析表明,五味子醇甲的抑制作用通过调节Mmp3、Mmp13、Adamts5和Cox2的表达减轻了骨关节炎软骨破坏。在核因子κB(NF-κB)信号通路中,五味子醇甲抑制了IL-1β诱导的IκB降解和p65磷酸化。总体而言,五味子醇甲通过阻断NF-κB信号通路降低了分解代谢因子的表达并防止了软骨破坏。因此,五味子醇甲减轻了OA进展,可用于开发新型OA药物疗法。