State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China; Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology, Macao 999078, China; Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China.
Pharmacol Res. 2022 Jan;175:106000. doi: 10.1016/j.phrs.2021.106000. Epub 2021 Nov 24.
Traditional Chinese medicine (TCM) has been long time used in China and gains ever-increasing worldwide acceptance. Er Miao San (EMS), a TCM formula, has been extensively used to treat inflammatory diseases, while its bioactive components and therapeutic mechanisms remain unclear. In this study, we conducted an integrative approach of network pharmacology and experimental study to elucidate the underlying mechanisms of EMS in treating human rheumatoid arthritis (RA) and other inflammatory conditions. Quercetin, wogonin and rutaecarpine were probably the main active compounds of EMS in RA treatment as they affected the most RA-related targets, and TNF-α, IL-6 and IL-1β were considered to be the core target proteins. The main compounds in EMS bound to these core proteins, which was further confirmed by molecular docking and bio-layer interferometry (BLI) analysis. Moreover, the potential molecular mechanisms of EMS predicted from network pharmacology analysis, were validated in vivo and in vitro experiments. EMS was found to inhibit the production of NO, TNF-α and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells; reduce xylene-induced mouse ear edema; and decrease the incidence of carrageenan-induced rat paw edema. The carrageenan-induced up-regulation of TNF-α, IL-6 and IL-1β mRNA expression in rat paws was down-regulated by EMS, consistent with the network pharmacology results. This study provides evidence that EMS plays a critical role in anti-inflammation via suppressing inflammatory cytokines, indicating that EMS is a candidate herbal drug for further investigation in treating inflammatory and arthritic conditions.
中药（TCM）在中国已有很长时间的应用历史，并在全球范围内得到越来越多的认可。二妙散（EMS）是一种中药方剂，已广泛用于治疗炎症性疾病，但它的生物活性成分和治疗机制仍不清楚。在这项研究中，我们采用网络药理学和实验研究相结合的方法，阐明了 EMS 治疗人类类风湿关节炎（RA）和其他炎症性疾病的潜在机制。槲皮素、黄芩素和吴茱萸碱可能是 EMS 治疗 RA 的主要活性化合物，因为它们影响了最多的 RA 相关靶点，而 TNF-α、IL-6 和 IL-1β被认为是核心靶蛋白。EMS 中的主要化合物与这些核心蛋白结合，这进一步通过分子对接和生物层干涉（BLI）分析得到了证实。此外，从网络药理学分析预测的 EMS 的潜在分子机制，在体内和体外实验中得到了验证。研究发现，EMS 抑制了脂多糖（LPS）刺激的 RAW264.7 细胞中 NO、TNF-α和 IL-6 的产生；减少二甲苯诱导的小鼠耳肿胀；降低角叉菜胶诱导的大鼠足肿胀。EMS 还下调了角叉菜胶诱导的大鼠足 TNF-α、IL-6 和 IL-1β mRNA 表达的上调，与网络药理学结果一致。这项研究提供了证据，表明 EMS 通过抑制炎症细胞因子在抗炎中发挥关键作用，表明 EMS 是一种候选草药药物，可进一步研究用于治疗炎症和关节炎疾病。
