Cai Jia-Luo, Li Xiao-Ping, Zhu Yi-Lin, Deng Gui-Ming, Yang Lei, Xia Xin-Hua, Yi Gang-Qiang, Chen Xin-Yu
the First Hospital Affiliated to Hunan University of Chinese Medicine Changsha 410000, China ZHANG Zhi-guo Inheritance Studio of the National Expert of Traditional Chinese Medicine Changsha 410000, China.
the First Hospital Affiliated to Hunan University of Chinese Medicine Changsha 410000, China.
Zhongguo Zhong Yao Za Zhi. 2022 Feb;47(4):1039-1050. doi: 10.19540/j.cnki.cjcmm.20210924.401.
This study analyzed the molecular mechanism of Huangjing Qianshi Decoction(HQD) in the treatment of prediabetes based on network pharmacology and molecular docking. The active components of HQD were identified and screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP, http://Lsp.nwu.edu.cn/tcmsp.php) and then the targets of the components and the genes related to prediabetes were retrieved, followed by identifying the common targets of the decoction and the disease. The medicinal component-target network was constructed by Cytoscape to screen key components. The protein-protein interaction(PPI) network was established by STRING and hub genes were identified by Cytoscape-CytoNCA, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) of the hub genes with R-clusterProfi-ler. Thereby, the possible signaling pathways were predicted and the molecular mechanism was deduced. A total of 79 active components of HQD and 785 diabetes-related targets of the components were screened out. The hub genes mainly involved the GO terms of tricarboxylic acid cycle, peptide binding, amide binding, hydrolase activity, and kinase activity regulation, and the KEGG pathways of AGE-RAGE signaling pathway, TNF signaling pathway, AMPK signaling pathway, IL-17 signaling pathway, and insulin signaling pathway. Western blot result showed that HQD-containing serum significantly reduced the expression of AKT1, AGE, and RAGE proteins in insulin resistance model cells. HQD's treatment of prediabetes is characterized by multiple pathways, multiple targets, and multiple levels. The main mechanism is that the components zhonghualiaoine, baicalein, kaempferol, and luteolin act on AKT1 and inhibit the AGE-RAGE axis.
本研究基于网络药理学和分子对接分析了黄精芡实汤治疗糖尿病前期的分子机制。基于中药系统药理学数据库及分析平台（TCMSP，http://Lsp.nwu.edu.cn/tcmsp.php）鉴定并筛选了黄精芡实汤的活性成分，随后检索这些成分的靶点以及与糖尿病前期相关的基因，进而确定该汤剂与疾病的共同靶点。利用Cytoscape构建药物成分-靶点网络以筛选关键成分。通过STRING建立蛋白质-蛋白质相互作用（PPI）网络，并利用Cytoscape-CytoNCA鉴定枢纽基因，随后使用R语言的clusterProfiler对枢纽基因进行基因本体（GO）术语富集分析和京都基因与基因组百科全书（KEGG）通路分析。由此预测可能的信号通路并推导分子机制。共筛选出黄精芡实汤的79种活性成分及其785个与糖尿病相关的靶点。枢纽基因主要涉及三羧酸循环、肽结合酰胺结合、水解酶活性和激酶活性调节等GO术语，以及AGE-RAGE信号通路、TNF信号通路、AMPK信号通路、IL-17信号通路和胰岛素信号通路等KEGG通路。蛋白质免疫印迹结果显示，含黄精芡实汤血清显著降低胰岛素抵抗模型细胞中AKT1、AGE和RAGE蛋白的表达。黄精芡实汤治疗糖尿病前期具有多途径、多靶点、多层次的特点。其主要机制是中华蓼碱、黄芩素、山奈酚和木犀草素等成分作用于AKT1并抑制AGE-RAGE轴。
