Integrated Network and Experimental Pharmacology for Deciphering the Medicinal Substances and Multiple Mechanisms of Duhuo Jisheng Decoction in Osteoarthritis Therapy.
Integrated Network and Experimental Pharmacology for Deciphering the Medicinal Substances and Multiple Mechanisms of Duhuo Jisheng Decoction in Osteoarthritis Therapy.
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DOI：
10.1155/2020/7275057
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Shen J
中科院分区：
文献类型：
--
作者：
Xiao W;Sun W;Lian H;Shen J
骨性关节炎是目前世界范围内最常见的关节疾病。在过去的几十年里，草药疗法在治疗骨性关节炎方面取得了显著的进步。独活积生汤是由15种中草药组成的中药方剂，在中国治疗骨性关节炎中有着长期的实践经验。然而，其治疗机制尚未全面阐明。本论文从整体网络和实验药理学两个方面对丹参解毒散的治疗物质和作用机制进行了研究。在网络分析的基础上，评价了各中药对骨性关节炎治疗的贡献。此外，还丰富了一系列潜在的靶点和信号通路，可能参与DHJS的治疗作用和机制。进一步的实验结果表明，丹参解毒散可抑制肿瘤坏死因子α、IL-6、MMP1、MMP9、MMP13和ADAMTS-5的表达，抑制NF-κB和p38MAPK信号通路，激活AMPK-SIRT1信号通路，抑制软骨细胞凋亡，从而协同作用于骨关节炎的治疗。我们的工作表明，DHJS通过在多靶点和多途径上协同作用，可能在骨性关节炎治疗中非常有前景。
Osteoarthritis (OA) is currently the most common joint disorder worldwide. In last decades, herbal remedies have achieved a significant advancement in the treatment of OA. Duhuo Jisheng Decoction (DHJS), an herbal formula consisting of 15 medicinal herbs, has a long-time practice in OA therapy in China. However, its therapeutic mechanisms have not been comprehensively elucidated. In the present work, integrated network and experimental pharmacology were performed for investigating the therapeutic substances and mechanisms of DHJS. Based on network analysis, the contribution of each herb to OA therapy was evaluated. Furthermore, a series of potential targets and signaling pathways were enriched, which could be involved in the therapeutic effects and mechanisms of DHJS. Further experimental results indicated that DHJS attenuated TNFα, IL-6, MMP-1, MMP-9, MMP-13, and ADAMTs-5 expression, inhibited NF-κB and p38 MAPK signaling pathway, activated AMPK-SIRT1 signaling pathway, and suppressed chondrocyte apoptosis, which synergistically contributed to OA therapy. Our work demonstrated that DHJS could be very promising for OA therapy through synergistically acting on multitargets and multipathways.
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