Systems pharmacology-based study of Tanreqing injection in airway mucus hypersecretion
Systems pharmacology-based study of Tanreqing injection in airway mucus hypersecretion
复制标题
痰热清注射液治疗气道粘液分泌过多的系统药理学研究
DOI：
10.1016/j.jep.2019.112425
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发表时间：
2020-03-01
影响因子：
5.4
通讯作者：
Jiang, Hongli
中科院分区：
文献类型：
--
作者：
Liu, Wei;Zhang, Xiawei;Jiang, Hongli
民族药理学相关性：粘液高分泌（MH）被认为是许多气道炎症性疾病的重要病理生理和临床特征。MUC 5AC是气道粘液的主要成分。痰热清注射液是一种临床应用广泛的治疗呼吸道炎症的中药制剂。然而，目前还没有一个完整的网络药理学方法来理解TRQ对MH的治疗机制。研究目的：本研究旨在探索TRQ治疗MH的系统水平潜在活性化合物和治疗机制。材料和方法：我们建立了基于药理学的系统策略，包括化合物筛选，靶点预测，并对TRQ的作用途径进行了鉴定，以推测其潜在的活性成分和治疗靶点。我们还应用化合物-靶点和靶点-疾病网络分析来评估TRQ的可能作用机制。然后，脂多糖（LPS）诱导的SD大鼠模型，以评估TRQ在治疗MH的效果，并验证可能的分子机制，预测在系统药理学approach.Results的全面化合物收集成功地产生55个化合物的候选人从TRQ。其中，11种与潜在靶点相关性高的化合物被确定为TRQ公式中的代表性和潜在活性成分。靶点鉴定揭示了172个潜在靶点，包括促炎细胞因子肿瘤坏死因子α（TNF-α）、白细胞介素IL-6和IL-8。通路分析揭示了TRQ在调节IL-17信号通路及其下游蛋白MUC 5AC中的可能作用。体内实验表明，TRQ能显著抑制LPS刺激的MUC 5AC的过度表达，并能在蛋白和mRNA水平上抑制TNF-α、IL-6、IL-8和IL-17A.Conclusions：基于系统药理学方法和体内实验，我们的工作为TRQ抗MH过程中潜在的活性成分和可能的治疗靶点提供了一般知识。这项工作可能会建议方向，进一步研究TRQ和提供更多的洞察力，更好地了解复杂的草药处方的化学和药理机制，在网络的角度来看。
Ethnopharmacological relevance: Mucus hypersecretion (MH) is recognized as a key pathophysiological and clinical feature of many airway inflammatory diseases. MUC5AC is a major component of airway mucus. Tanreqing injection (TRQ) is a widely used herbal formula for the treatment of respiratory inflammations for years in China. However, a holistic network pharmacology approach to understanding its therapeutic mechanisms against MH has not been pursued.Aim of the study: This study aimed to explore the systems-level potential active compounds and therapeutic mechanisms of TRQ in the treatment of MH.Materials and methods: We established systems pharmacology-based strategies comprising compound screenings, target predictions, and pathway identifications to speculate the potential active compounds and therapeutic targets of TRQ. We also applied compound-target and target-disease network analyses to evaluate the possible action mechanisms of TRQ. Then, lipopolysaccharide (LPS)-induced Sprague-Dawley (SD) rat model was constructed to assess the effect of TRQ in the treatment of MH and to validate the possible molecular mechanisms as predicted in systems pharmacology approach.Results: The comprehensive compound collection successfully generated 55 compound candidates from TRQ. Among them, 11 compounds with high relevance to the potential targets were defined as representative and potential active ingredients in TRQ formula. Target identification revealed 172 potential targets, including proinflammatory cytokines of tumor necrosis factor alpha(TNF-alpha), interleukin IL-6, and IL-8. Pathway analyses uncovered the possible action of TRQ in the regulation of IL-17 signaling pathway and its downstream protein MUC5AC. Then in vivo experiment indicated that TRQ could significantly inhibit LPS stimulated MUC5AC overproduction as well as the expression of TNF-alpha, IL-6, IL-8, and IL-17A, in both protein and mRNA levels.Conclusions: Based on the systems pharmacology method and in vivo experiment, our work provided a general knowledge on the potential active compounds and possible therapeutic targets of TRQ formula in its anti-MH process. This work might suggest directions for further research on TRQ and provide more insight into better understanding the chemical and pharmacological mechanisms of complex herbal prescriptions in a network perspective.