Wei Shizhang, Niu Ming, Wang Jian, Wang Jiabo, Su Haibin, Luo Shengqiang, Zhang Xiaomei, Guo Yanlei, Liu Liping, Liu Fengqun, Zhao Qingguo, Chen Hongge, Xiao Xiaohe, Zhao Pan, Zhao Yanling
Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China; Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.
China Military Institute of Chinese Medicine, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China.
Drug Des Devel Ther. 2016 Feb 19;10:733-43. doi: 10.2147/DDDT.S96964. eCollection 2016.
San-Cao Granule (SCG) has been used in patients with liver fibrosis for many years and has shown good effect. However, its mechanism of therapeutic action is not clear because of its complex chemical system. The purpose of our study is to establish a comprehensive and systemic method that can predict the mechanism of action of SCG in antihepatic fibrosis.
In this study, a "compound-target-disease" network was constructed by combining the SCG-specific and liver fibrosis-specific target proteins with protein-protein interactions, and network pharmacology was used to screen out the underlying targets and mechanisms of SCG for treatment of liver fibrosis. Then, some key molecules of the enriched pathway were chosen to verify the effects of SCG on liver fibrosis induced by thioacetamide (TAA).
This systematic approach had successfully revealed that 16 targets related to 11 SCG compounds were closely associated with liver fibrosis therapy. The pathway-enrichment analysis of them showed that the TGF-β1/Smad signaling pathway is relatively important. Animal experiments also proved that SCG could significantly ameliorate liver fibrosis by inhibiting the TGF-β1/Smad pathway.
SCG could alleviate liver fibrosis through the molecular mechanisms predicted by network pharmacology. Furthermore, network pharmacology could provide deep insight into the pharmacological mechanisms of Chinese herbal formulas.
三草颗粒(SCG)已用于肝纤维化患者多年,且显示出良好疗效。然而,由于其化学体系复杂,其治疗作用机制尚不清楚。我们研究的目的是建立一种全面且系统的方法,以预测SCG抗肝纤维化的作用机制。
在本研究中,通过将SCG特异性和肝纤维化特异性靶蛋白与蛋白质-蛋白质相互作用相结合构建了一个“化合物-靶标-疾病”网络,并利用网络药理学筛选出SCG治疗肝纤维化的潜在靶标和机制。然后,选择富集通路中的一些关键分子来验证SCG对硫代乙酰胺(TAA)诱导的肝纤维化的影响。
这种系统方法成功揭示了与11种SCG化合物相关的16个靶标与肝纤维化治疗密切相关。对它们的通路富集分析表明,TGF-β1/Smad信号通路相对重要。动物实验也证明,SCG可通过抑制TGF-β1/Smad通路显著改善肝纤维化。
SCG可通过网络药理学预测的分子机制减轻肝纤维化。此外,网络药理学可为深入了解中药方剂的药理机制提供帮助。