Abstract：
BACKGROUND: Knee osteoarthritis (KOA) is a common degenerative joint disease characterized by cartilage degradation, inflammation, and pain. Traditional Chinese Medicine, including JDJM (a herbal formula derived from the renowned Du Huo Ji Sheng Tang), has been used to alleviate symptoms of KOA, but its underlying mechanisms remain unclear.
OBJECTIVE: This study aims to elucidate the potential therapeutic mechanisms of JDJM in treating KOA through network pharmacology, weighted gene co-expression network analysis (WGCNA), molecular docking, and experimental validation in animal models.
METHODS: The active compounds of JDJM were identified through TCMSP database searches, and their potential targets were predicted using network pharmacology. WGCNA was employed to identify key modules and hub genes associated with KOA. Molecular docking was performed to assess the binding affinities of key compounds to critical inflammatory targets. Molecular dynamics (MD) simulations were used to evaluate the stability of the protein-ligand complexes. An experimental KOA model in rabbits was used to validate the therapeutic effects of JDJM. Histopathological examinations and inflammatory marker analyses were conducted to confirm the findings.
RESULTS: Network pharmacology and WGCNA analyses identified 21 key targets and pathways potentially involved in the therapeutic effects of JDJM. Molecular docking results showed that Glyasperin C had the highest docking scores with EGF and IL-1β, followed by Stigmasterol with IL-6, Myricanone with INS, and Sesamin with VEGFA. MD simulations confirmed the stability of these protein-ligand complexes, indicating strong and stable interactions. In the rabbit KOA model, JDJM treatment significantly improved knee joint morphology and reduced the levels of inflammatory markers, such as IL-6 and TNF-α. Histopathological analysis revealed reduced cartilage degradation and inflammation in the JDJM-treated group compared to controls.
CONCLUSIONS: JDJM exhibits promising anti-inflammatory and cartilage-protective effects, making it a potential therapeutic option for KOA patients. Further experimental and clinical studies are warranted to confirm these findings and translate them into clinical practice..
OBJECTIVE: This study aims to elucidate the potential therapeutic mechanisms of JDJM in treating KOA through network pharmacology, weighted gene co-expression network analysis (WGCNA), molecular docking, and experimental validation in animal models.
METHODS: The active compounds of JDJM were identified through TCMSP database searches, and their potential targets were predicted using network pharmacology. WGCNA was employed to identify key modules and hub genes associated with KOA. Molecular docking was performed to assess the binding affinities of key compounds to critical inflammatory targets. Molecular dynamics (MD) simulations were used to evaluate the stability of the protein-ligand complexes. An experimental KOA model in rabbits was used to validate the therapeutic effects of JDJM. Histopathological examinations and inflammatory marker analyses were conducted to confirm the findings.
RESULTS: Network pharmacology and WGCNA analyses identified 21 key targets and pathways potentially involved in the therapeutic effects of JDJM. Molecular docking results showed that Glyasperin C had the highest docking scores with EGF and IL-1β, followed by Stigmasterol with IL-6, Myricanone with INS, and Sesamin with VEGFA. MD simulations confirmed the stability of these protein-ligand complexes, indicating strong and stable interactions. In the rabbit KOA model, JDJM treatment significantly improved knee joint morphology and reduced the levels of inflammatory markers, such as IL-6 and TNF-α. Histopathological analysis revealed reduced cartilage degradation and inflammation in the JDJM-treated group compared to controls.
CONCLUSIONS: JDJM exhibits promising anti-inflammatory and cartilage-protective effects, making it a potential therapeutic option for KOA patients. Further experimental and clinical studies are warranted to confirm these findings and translate them into clinical practice..
摘要：
背景：膝骨关节炎（KOA）是一种常见的退行性关节疾病，其特征是软骨退化，炎症,和痛苦。中药,包括JDJM（源自著名的杜霍吉生堂的草药配方），已经被用来缓解KOA的症状，但其潜在机制仍不清楚。
目的：本研究旨在阐明JDJM通过网络药理学治疗KOA的潜在治疗机制，加权基因共表达网络分析(WGCNA)，分子对接,和动物模型的实验验证。
方法：通过TCMSP数据库搜索鉴定了JDJM的活性化合物，他们的潜在目标是使用网络药理学预测。WGCNA用于鉴定与KOA相关的关键模块和枢纽基因。进行分子对接以评估关键化合物与关键炎症靶标的结合亲和力。分子动力学(MD)模拟用于评估蛋白质-配体复合物的稳定性。使用兔的实验性KOA模型来验证JDJM的治疗效果。进行组织病理学检查和炎症标志物分析以确认发现。
结果：网络药理学和WGCNA分析确定了21个可能参与JDJM治疗效果的关键靶点和途径。分子对接结果显示,GlyasperinC与EGF和IL-1β的对接得分最高,其次是豆甾醇和IL-6，Myricanone和INS，和塞萨明与VEGFA。MD模拟证实了这些蛋白质-配体复合物的稳定性，表明强烈和稳定的相互作用。在兔KOA模型中,JDJM治疗显著改善膝关节形态，降低炎症标志物水平，如IL-6和TNF-α。组织病理学分析显示，与对照组相比，JDJM治疗组的软骨降解和炎症减少。
结论：JDJM具有良好的抗炎和软骨保护作用，使其成为KOA患者的潜在治疗选择。需要进一步的实验和临床研究来证实这些发现并将其转化为临床实践。。
目的：本研究旨在阐明JDJM通过网络药理学治疗KOA的潜在治疗机制，加权基因共表达网络分析(WGCNA)，分子对接,和动物模型的实验验证。
方法：通过TCMSP数据库搜索鉴定了JDJM的活性化合物，他们的潜在目标是使用网络药理学预测。WGCNA用于鉴定与KOA相关的关键模块和枢纽基因。进行分子对接以评估关键化合物与关键炎症靶标的结合亲和力。分子动力学(MD)模拟用于评估蛋白质-配体复合物的稳定性。使用兔的实验性KOA模型来验证JDJM的治疗效果。进行组织病理学检查和炎症标志物分析以确认发现。
结果：网络药理学和WGCNA分析确定了21个可能参与JDJM治疗效果的关键靶点和途径。分子对接结果显示,GlyasperinC与EGF和IL-1β的对接得分最高,其次是豆甾醇和IL-6，Myricanone和INS，和塞萨明与VEGFA。MD模拟证实了这些蛋白质-配体复合物的稳定性，表明强烈和稳定的相互作用。在兔KOA模型中,JDJM治疗显著改善膝关节形态，降低炎症标志物水平，如IL-6和TNF-α。组织病理学分析显示，与对照组相比，JDJM治疗组的软骨降解和炎症减少。
结论：JDJM具有良好的抗炎和软骨保护作用，使其成为KOA患者的潜在治疗选择。需要进一步的实验和临床研究来证实这些发现并将其转化为临床实践。。
