He Shuaibing, Chen Hantao, Yi Yanfeng, Hou Diandong, Fu Xuyan, Xie Jinlu, Zhang Juan, Liu Chongbin, Ru Xiaochen, Wang Juan
Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, School of Medicine, Huzhou Central Hospital, Huzhou University, Huzhou, China.
Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, China.
Front Pharmacol. 2024 Jun 28;15:1406188. doi: 10.3389/fphar.2024.1406188. eCollection 2024.
As a new discipline, network pharmacology has been widely used to disclose the material basis and mechanism of Traditional Chinese Medicine in recent years. However, numerous researches indicated that the material basis of TCMs identified based on network pharmacology was the mixtures of beneficial and harmful substances rather than the real material basis. In this work, taking the anti-NAFLD (non-alcoholic fatty liver disease) effect of Bai Shao (BS) as a case, we attempted to propose a novel bioinformatics strategy to uncover the material basis and mechanism of TCMs in a precise manner. In our previous studies, we have done a lot work to explore TCM-induced hepatoprotection. Here, by integrating our previous studies, we developed a novel computational pharmacology method to identify hepatoprotective ingredients from TCMs. Then the developed method was used to discover the material basis and mechanism of Bai Shao against Non-alcoholic fatty liver disease by combining with the techniques of molecular network, microarray data analysis, molecular docking, and molecular dynamics simulation. Finally, literature verification method was utilized to validate the findings. A total of 12 ingredients were found to be associated with the anti-NAFLD effect of BS, including monoterpene glucosides, flavonoids, triterpenes, and phenolic acids. Further analysis found that IL1-β, IL6, and JUN would be the key targets. Interestingly, molecular docking and molecular dynamics simulation analysis showed that there indeed existed strong and stable binding affinity between the active ingredients and the key targets. In addition, a total of 23 NAFLD-related KEGG pathways were enriched. The major biological processes involved by these pathways including inflammation, apoptosis, lipid metabolism, and glucose metabolism. Of note, there was a great deal of evidence available in the literature to support the findings mentioned above, indicating that our method was reliable. In summary, the contributions of this work can be summarized as two aspects as follows. Firstly, we systematically elucidated the material basis and mechanism of BS against NAFLD from multiple perspectives. These findings further enhanced the theoretical foundation of BS on NAFLD. Secondly, a novel computational pharmacology research strategy was proposed, which would assist network pharmacology to uncover the scientific connotation TCMs in a more precise manner.
作为一门新兴学科，网络药理学近年来已被广泛用于揭示中药的物质基础和作用机制。然而，大量研究表明，基于网络药理学确定的中药物质基础是有益和有害物质的混合物，而非真正的物质基础。在本研究中，以白芍（BS）的抗非酒精性脂肪性肝病（NAFLD）作用为例，我们尝试提出一种新的生物信息学策略，以精确揭示中药的物质基础和作用机制。在我们之前的研究中，我们做了大量工作来探索中药诱导的肝脏保护作用。在此，通过整合我们之前的研究，我们开发了一种新的计算药理学方法来从中药中鉴定肝脏保护成分。然后，将所开发的方法与分子网络、微阵列数据分析、分子对接和分子动力学模拟技术相结合，用于发现白芍抗非酒精性脂肪性肝病的物质基础和作用机制。最后，利用文献验证方法对研究结果进行验证。共发现12种成分与白芍的抗非酒精性脂肪性肝病作用相关，包括单萜糖苷、黄酮类、三萜类和酚酸类。进一步分析发现，IL1-β、IL6和JUN将是关键靶点。有趣的是，分子对接和分子动力学模拟分析表明，活性成分与关键靶点之间确实存在强而稳定的结合亲和力。此外，共富集了23条与非酒精性脂肪性肝病相关的KEGG通路。这些通路涉及的主要生物学过程包括炎症、凋亡、脂质代谢和葡萄糖代谢。值得注意的是，文献中有大量证据支持上述发现，表明我们的方法是可靠的。总之，本研究的贡献可概括为以下两个方面。首先，我们从多个角度系统阐明了白芍抗非酒精性脂肪性肝病的物质基础和作用机制。这些发现进一步加强了白芍治疗非酒精性脂肪性肝病的理论基础。其次，提出了一种新的计算药理学研究策略，这将有助于网络药理学更精确地揭示中药的科学内涵。
