An Integrative Pharmacology Model for Decoding the Underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid Arthritis.
An Integrative Pharmacology Model for Decoding the Underlying Therapeutic Mechanisms of Ermiao Powder for Rheumatoid Arthritis.
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DOI：
10.3389/fphar.2022.801350
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发表时间：
2022
影响因子：
5.6
通讯作者：
Guan D
中科院分区：
文献类型：
--
作者：
Wu J;Wang K;Liu Q;Li Y;Huang Y;Liu Y;Cai J;Yin C;Li X;Yu H;Meng W;Wang H;Lu A;Li Y;Guan D
类风湿性关节炎（RA）作为一种全身性炎症性关节炎疾病，具有复杂性和遗传性。中医药在治疗复杂性疾病方面具有明显优势，目前已有多种中药方剂对类风湿性关节炎有较好的治疗效果。临床和药理研究表明，以黄柏为主要成分的二妙散具有清热解毒、活血化瘀的作用。(PAR)和兰（Lancea（Thunb.）DC. (ALD)可用于治疗类风湿关节炎。目前，对PAR和ALD的抗炎作用机制研究较多，对其协同作用的分子机制研究较少。本研究采用整体药理学策略，探讨二妙散治疗类风湿关节炎的协同分子机制。为了探索PAR和ALD的潜在协同作用机制，我们首先建立了一个新的数学模型，计算了126个活性组分和85个活性组分的贡献分数，这些活性组分贡献了总贡献分数的90%，并保留来构建协同功能空间。然后，应用背包算法从85个活动组件中识别出核心协调功能组件。最后得到了汉黄芩素、丹皮酚、咖啡酸乙酯、木兰花碱等37个潜在配位功能组分群。同时，对CFCG的靶点进行功能富集分析，以探讨PAR和ALD的潜在协同分子机制。结果表明，CFCG通过协同靶向作用于免疫和炎症相关信号通路的基因，如磷脂酰肌醇3-激酶/蛋白激酶B信号通路、丝裂原活化蛋白激酶信号通路、肿瘤坏死因子信号通路和核因子-κ B信号通路，从而达到治疗RA的目的。通过对接实验和体外实验对CFCG的亲和力进行了预测和验证，进一步证实了该方法的可靠性。本研究的整体药理学策略，包括CFCG的鉴定和验证，可为探讨中医药治疗复杂疾病的协同作用机制提供方法学参考，有助于提高我们对协同作用机制的认识。
As a systemic inflammatory arthritis disease, rheumatoid arthritis (RA) is complex and hereditary. Traditional Chinese medicine (TCM) has evident advantages in treating complex diseases, and a variety of TCM formulas have been reported that have effective treatment on RA. Clinical and pharmacological studies showed that Ermiao Powder, which consists of Phellodendron amurense Rupr. (PAR) and Atractylodes lancea (Thunb.) DC. (ALD), can be used in the treatment of RA. Currently, most studies focus on the anti-inflammatory mechanism of PAR and ALD and are less focused on their coordinated molecular mechanism. In this research, we established an integrative pharmacological strategy to explore the coordinated molecular mechanism of the two herbs of Ermiao Powder in treating RA. To explore the potential coordinated mechanism of PAR and ALD, we firstly developed a novel mathematical model to calculate the contribution score of 126 active components and 85 active components, which contributed 90% of the total contribution scores that were retained to construct the coordinated functional space. Then, the knapsack algorithm was applied to identify the core coordinated functional components from the 85 active components. Finally, we obtained the potential coordinated functional components group (CFCG) with 37 components, including wogonin, paeonol, ethyl caffeate, and magnoflorine. Also, functional enrichment analysis was performed on the targets of CFCG to explore the potential coordinated molecular mechanisms of PAR and ALD. The results indicated that the CFCG could treat RA by coordinated targeting to the genes involved in immunity and inflammation-related signal pathways, such as phosphatidylinositol 3‑kinase/protein kinase B signaling pathway, mitogen-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, and nuclear factor-kappa B signaling pathway. The docking and in vitro experiments were used to predict the affinity and validate the effect of CFCG and further confirm the reliability of our method. Our integrative pharmacological strategy, including CFCG identification and verification, can provide the methodological references for exploring the coordinated mechanism of TCM in treating complex diseases and contribute to improving our understanding of the coordinated mechanism.
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影响因子：
3.1
作者：
Cao, Yun-Xiang;Huang, Dan;Wang, Yuan
通讯作者：
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影响因子：
14.9
作者：
wwPDB consortium
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wwPDB consortium
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