College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
College of Preclinical Medical, Nanjing University of Chinese Medicine, Nanjing 210046, China.
J Ethnopharmacol. 2015 Jun 20;168:1-16. doi: 10.1016/j.jep.2015.03.035. Epub 2015 Mar 28.
Modified Simiaowan (MSW) is a traditional Chinese medicine (TCM) formula and is widely used as a clinically medication formula for its efficiency in treating gouty diseases.To predict the active ingredients in MSW and uncover the rationality of herb combinations of MSW.
Three drug-target networks including the "candidate ingredient-target network" (cI-cT) that links the candidate ingredients and targets, the "core ingredient-target-pathway network" connecting core potential ingredients and targets through related pathways, and the "rationality of herb combinations of MSW network", which was derived from the cI-cT network, were developed to dissect the active ingredients in MSW and relationship between ingredients in herb combinations and their targets for gouty diseases. On the other hand, herbal ingredients comparisons were also conducted based on six physicochemical properties to investigate whether the herbs in MSW are similar in chemicals. Moreover, HUVEC viability and expression levels of ICAM-1 induced by monosodium urate (MSU) crystals were assessed to determine the activities of potential ingredients in MSW.
Predicted by the core ingredient-target-pathway network, we collected 30 core ingredients in MSW and 25 inflammatory cytokines and uric acid synthetase or transporters, which are effective for gouty treatment through some related pathways. Experimental results also confirmed that those core ingredients could significantly increase HUVEC viability and attenuate the expression of ICAM-1, which supported the effectiveness of MSW in treating gouty diseases. Moreover, heat-clearing and dampness-eliminating herbs in MSW have similar physicochemical properties, which stimulate all the inflammatory and uric acid-lowing targets respectively, while the core drug and basic prescription in MSW stimulate the major and almost all the core targets, respectively.
Our work successfully predicts the active ingredients in MSW and explains the cooperation between these ingredients and corresponding targets through related pathways for gouty diseases, and provides basis for an alternative approach to investigate the rationality of herb combinations of MSW on the network pharmacology level, which might be beneficial to drug development and applications.
改良 Simiaowan (MSW) 是一种中药配方，因其在治疗痛风疾病方面的疗效而被广泛用作临床用药配方。为了预测 MSW 中的活性成分，并揭示 MSW 中草药组合的合理性。
构建了三个药物-靶标网络，包括连接候选成分和靶标的“候选成分-靶标网络”（cI-cT）、通过相关途径连接核心潜在成分和靶标的“核心成分-靶标-途径网络”，以及源自 cI-cT 网络的“MSW 草药组合合理性网络”，以剖析 MSW 中的活性成分以及草药组合中的成分与其治疗痛风疾病靶标之间的关系。另一方面，还基于六种物理化学性质进行了草药成分比较，以研究 MSW 中的草药在化学成分上是否相似。此外，还评估了潜在成分在 MSW 中对尿酸单钠 (MSU) 晶体诱导的 HUVEC 活力和 ICAM-1 表达水平的影响，以确定 MSW 中潜在成分的活性。
通过核心成分-靶标-途径网络预测，我们收集了 MSW 中的 30 种核心成分和 25 种炎症细胞因子和尿酸合成酶或转运体，这些成分通过一些相关途径对痛风的治疗有效。实验结果也证实，这些核心成分可显著提高 HUVEC 的活力，并减弱 ICAM-1 的表达，这支持了 MSW 治疗痛风疾病的有效性。此外，MSW 中的清热利湿草药具有相似的物理化学性质，分别刺激所有炎症和降尿酸靶点，而 MSW 中的核心药物和基本处方则分别刺激主要和几乎所有核心靶点。
我们的工作成功预测了 MSW 中的活性成分，并通过相关途径解释了这些成分与相应靶标之间的协同作用，为在网络药理学水平上研究 MSW 中草药组合的合理性提供了依据，这可能有利于药物开发和应用。
