Liu Fangzhou, Li Yuanbai, Li Meng, Wang Jing, Zhang Yiying, Du Yu, Yang Yang
Institute of Information on Traditional Chinese Medicine, Beijing, China.
Evid Based Complement Alternat Med. 2020 Jun 26;2020:4062813. doi: 10.1155/2020/4062813. eCollection 2020.
To investigate the pharmacological mechanism of the iridoid glycosides from in Jiangxi province by network pharmacology. To provide a valuable research strategy for the rational use and in-depth research and development of from Jiangxi.
Previous research results of our group show that the contents of iridoid glycosides in from Jiangxi province have a significant difference compared with other regions ( < 0.05). Based on our previous experimental results, this study selected six characteristic high-content bioactive iridoid glycosides components of from Jiangxi province as candidate components. TCMSP database was used to obtain the process parameters of absorption, distribution, metabolism, and excretion (ADME) of candidate components. PubChem and SWISS online database were used to predict the related targets. Cytoscape software was used to the construct compound-target-disease (C-T-D) network of the iridoid glycosides ingredients. Furthermore, the GO biological process analysis and the pathway enrichment analysis were carried out using the CTD online analysis platform; then, an illustrated network that contains the main "chemicals-targets-pathway (C-T-P)" was constructed to analyze main biological pathways for obtaining the deep mechanism of in Jiangxi.
6 iridoid glycosides, namely geniposide, gardenoside, geniposidic acid, genipin 1-gentiobioside, gardoside, and shanzhiside, from in Jiangxi province were obtained as candidate components through previous work and network pharmacology screening. 36 corresponding targets were acted, such as BCL2, MAPT, F2, BCL2L1, PRKCD, PRKCB, HIF1A, and PRKCA. These targets could joint in pathways, such as signaling by GPCR, neuroactive ligand-receptor interaction, inflammatory mediator regulation of TRP channels, and ion channel transport. Interestingly, these pathways were highly associated with liver diseases, neurological diseases, hypertension, neoplasms, hyperalgesia, and inflammation. Remarkably, we boldly speculate that the from Jiangxi province can play a pharmacological role in hepatic encephalopathy through regulating multiple signaling pathways in an integrated manner.
The method based on system pharmacology could help to find the key targets of characteristic high-content chemical constituents of herb from different producing areas, the signaling pathway and disease network of TCM, and provide useful information and data support for giving a further study on traditional Chinese medicine resources in different regions of China.
采用网络药理学方法研究江西某药材中环烯醚萜苷类成分的药理作用机制,为江西该药材的合理应用及深入研发提供有价值的研究策略。
本课题组前期研究结果表明,江西该药材中环烯醚萜苷类成分的含量与其他地区相比有显著差异(P<0.05)。基于前期实验结果,本研究选取江西该药材中6种特征性高含量生物活性环烯醚萜苷类成分作为候选成分。利用TCMSP数据库获取候选成分的吸收、分布、代谢和排泄(ADME)过程参数。使用PubChem和SWISS在线数据库预测相关靶点。运用Cytoscape软件构建江西该药材中环烯醚萜苷类成分的化合物-靶点-疾病(C-T-D)网络。此外,利用CTD在线分析平台进行GO生物学过程分析和通路富集分析;构建包含主要“化学物质-靶点-通路(C-T-P)”的可视化网络,分析主要生物学通路,以深入了解江西该药材的作用机制。
通过前期工作及网络药理学筛选,确定江西该药材中的6种环烯醚萜苷类成分,即栀子苷、京尼平苷、栀子苷酸、京尼平-1-龙胆双糖苷、栀子黄素和山栀苷甲酯为候选成分。这些成分作用于36个相应靶点,如BCL2、MAPT、F2、BCL2L1、PRKCD、PRKCB、HIF1A和PRKCA等。这些靶点参与多种信号通路,如GPCR信号通路、神经活性配体-受体相互作用、炎症介质对TRP通道的调节以及离子通道转运等。有趣的是,这些通路与肝脏疾病、神经系统疾病、高血压、肿瘤、痛觉过敏和炎症密切相关。值得注意的是,我们大胆推测江西该药材可能通过综合调节多条信号通路在肝性脑病中发挥药理作用。
基于系统药理学的方法有助于发现不同产地药材特征性高含量化学成分的关键靶点、中药的信号通路及疾病网络,为进一步研究我国不同地区的中药资源提供有用的信息和数据支持。