Verification of pain-related neuromodulation mechanisms of icariin in knee osteoarthritis
Verification of pain-related neuromodulation mechanisms of icariin in knee osteoarthritis
复制标题
淫羊藿苷对膝骨关节炎疼痛相关神经调节机制的验证
DOI：
10.1016/j.biopha.2021.112259
复制
发表时间：
2021-10-01
影响因子：
7.5
通讯作者：
Asakawa, Tetsuya
中科院分区：
文献类型：
--
作者：
Li, Xihai;Xu, Yunteng;Asakawa, Tetsuya
膝关节骨关节炎（KOA）是一种常见病，无特效治疗。淫羊藿苷（伊卡）被认为是KOA的代理人。本研究旨在探讨伊卡对KOA疼痛的神经调节机制。设计了三个实验：（1）在体内外验证伊卡的治疗效果;（2）通过功能磁共振成像（fMRI）和病毒逆行追踪（VRT）探索伊卡治疗中潜在的疼痛相关神经调节通路;（3）通过基于串联质量标签（TMT）的定量蛋白质组学和生物信息学分析确定疼痛相关靶点。实验1验证了伊卡在OA动物和细胞模型中的功效。实验2发现一系列与KOA相关的脑区被伊卡治疗逆转，表明疼痛相关的下丘脑介导的神经调节通路和内源性大麻素（EC）相关通路有助于伊卡机制。实验3探索并证实了四个疼痛相关基因参与KOA和伊卡治疗。我们证实了疼痛相关的神经调节机制在伊卡治疗中的关键作用与其镇痛作用相关。我们的研究结果有助于考虑伊卡作为一种新的治疗KOA。
Knee osteoarthritis (KOA) is a common disease with no specific treatment. Icariin (ICA) is considered an agent for KOA. This study aimed to confirm the pain-related neuromodulation mechanisms of ICA on KOA. Three experiments were designed: (1) verifying the therapeutic effects of ICA in vivo and in vitro, (2) exploring the potential pain-related neuromodulation pathways involved in ICA treatment by functional magnetic resonance imaging (fMRI) and virus retrograde tracing (VRT) and (3) confirming the pain-related targets by tandem mass tag (TMT)-based quantitative proteomics and bioinformatic analyses. Experiment 1 verified the efficacy of ICA in OA animal and cell models. Experiment 2 found a series of brain regions associated with KOA reversed by ICA treatment, indicating that a pain-related hypothalamic-mediated neuromodulation pathway and an endocannabinoid (EC)-related pathway contribute to ICA mechanisms. Experiment 3 explored and confirmed four pain-related genes involved in KOA and ICA treatment. We confirmed the key role of pain-related neuromodulation mechanisms in ICA treatment associated with its analgesic effect. Our findings contribute to considering ICA as a novel therapy for KOA.