Li Na, Zhang Xin-Zhuang, Wang Yan-Ru, Cao Liang, Ding Gang, Wang Zhen-Zhong, Xiao Wei, Xu Xiao-Jie
State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process and Jiangsu Kanion Parmaceutical Co., Ltd., Lianyungang 222002, China.
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Zhongguo Zhong Yao Za Zhi. 2016 May;41(9):1706-1712. doi: 10.4268/cjcmm20160922.
Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Tongsaimai tablets for atherosclerosis. In molecular docking and molecular-target protein network analysis, 97 molecules in Tongsaimai tablets showed good interaction with the atherosclerosis-related target protein (docking score ≥ 7), and 37 molecules of them could act on more than 2 targets (≥ 2) with higher betweenness, suggesting that these 37 molecules might be the main active compounds group in Tongsaimai tablets for atherosclerosis treatment. Furthermore, the predicted active compounds contained more flavonoids and saponins, reminding more attention should be paid on flavonoids and saponins in study of effective compounds and quality standards of Tongsaimai tablets. Targets network analysis showed that, the active compounds of Tongsaimai tablets could regulate inflammation, stabilize plaque, protect vascular endothelial cell, regulate blood lipid and inhibit blood coagulation through acting on the main 22 target proteins, such as Toll-like receptors (TLR1, TLR2), matrix metalloproteinase (MMP1, MMP2, MMP3, MMP9), angiotensin converting enzyme (ACE), leukotriene A4 hydrolase (LTA4-H), 5-lipoxidase (5-LOX), peroxisome proliferators-activated receptors (PPARα, PPARγ). These active compounds can participate in regulating different pathologic stages of atherosclerosis and thus treat atherosclerosis finally. This study revealed the main active compounds and possible mechanism of Tongsaimai tablets for treatment of atherosclerosis and meanwhile, verified the characteristics of multi-components, multi-targets and integral regulation for Tongsaimai tablets, providing theoretical references for the following systematic laboratory experiments on effective compounds and action mechanism of Tongsaimai Tablet.
本研究采用网络药理学方法探讨通塞脉片治疗动脉粥样硬化的活性成分及作用机制。在分子对接和分子靶点蛋白网络分析中，通塞脉片中97个分子与动脉粥样硬化相关靶点蛋白表现出良好的相互作用（对接分数≥7），其中37个分子可作用于2个以上靶点（≥2）且具有较高的介数，表明这37个分子可能是通塞脉片治疗动脉粥样硬化的主要活性成分组。此外，预测的活性成分中黄酮类和皂苷类较多，提示在通塞脉片有效成分及质量标准研究中应更多关注黄酮类和皂苷类。靶点网络分析表明，通塞脉片的活性成分可通过作用于22种主要靶点蛋白，如Toll样受体（TLR1、TLR2）、基质金属蛋白酶（MMP1、MMP2、MMP3、MMP9）、血管紧张素转换酶（ACE）、白三烯A4水解酶（LTA4-H）、5-脂氧合酶（5-LOX）、过氧化物酶体增殖物激活受体（PPARα、PPARγ）等来调节炎症、稳定斑块、保护血管内皮细胞、调节血脂和抑制凝血。这些活性成分可参与调节动脉粥样硬化的不同病理阶段，最终治疗动脉粥样硬化。本研究揭示了通塞脉片治疗动脉粥样硬化的主要活性成分及可能机制，同时验证了通塞脉片多成分、多靶点、整体调节的特点，为后续通塞脉片有效成分及作用机制的系统实验研究提供了理论参考。
