关键词: 大柴胡汤, 网络药理学, 高脂血症

Abstract:

To explore the potential targets and related signaling pathways of Dachaihu Decoction in treating hyperlipidemia, we obtained the active ingredients of the decoction by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) for eight Chinese herbal ingredients, namely Radix Bupleuri, Radix Scutellariae, Radix Paeoniae Alba, Rhizoma Pinelliae, Fructus Aurantii Immaturus, Ginger, Jujube, and Rhubarb. To obtain the disease target for hyperlipidemia, we searched the English keyword “hyperlipidemia” and compared and analyzed the drug target of Dachaihu Decoction with the target of hyperlipidemia disease through an online website. We then identified the intersection between the two as the target of Dachaihu Decoction for treating hyperlipidemia. We conducted a topological analysis to screen the key effective components of Dachaihu Decoction for treating hyperlipidemia based on their degree value. Then, the gene targets of Dachaihu Decoction for hyperlipidemia were imported into the String platform to identify the key interaction modules in the PPI network. We also used the cytohubba plug-in to screen the key genes of these modules. The online database platform DAVID was utilized to perform enrichment and analysis of the key module genes with the highest number of genes and scores. The study yielded 116 active ingredients and 294 targets as the drug targets of Dachaihu Decoction. Furthermore, a total of 1349 disease-related gene targets were obtained from the CTD database, OMIM database, and TCMIP platform. After comparing the drug targets of Dachaihu Decoction with the targets related to hyperlipidemia, a total of 168 targets were found to be involved in the treatment of hyperlipidemia by Dachaihu Decoction. Using the MCODE plug-in in Cytoscape software, eight key protein modules were identified in the PPI network. Further analysis of the first key module revealed the top 15 hub genes which may play important roles in the pharmacological effects of Dachaihu Decoction for treating hyperlipidemia. To further understand the underlying mechanism, GO function annotation and KEGG pathway enrichment analysis were performed for the genes included in the key modules using the DAVID database. Based on the GO function annotation, the biological process (BP) of the key module genes was mainly related to the positive regulation of transcription from the RNA polymerase II promoter, the negative regulation of apoptosis, and the response to drugs. The cellular component (CC) was mainly located in the extracellular space, extracellular area, and pits. The molecular function (MF) was mainly focused on enzyme binding, cytokine activity, and protein binding. The KEGG pathway enrichment analysis showed that the key module genes were involved in several signaling pathways, including the hepatitis B signaling pathway, TNF signaling pathway, tumor-related signaling pathway, and PI3K-AKT signaling pathway. These pathways are known to be associated with inflammation, apoptosis, and cell growth, which are all critical processes in the development of hyperlipidemia. In conclusion, it appeared that Dachaihu Decoction could potentially be effective in the treatment of hyperlipidemia by regulating the expression of key genes, such as MMP9 and MAPK2, as well as the PI3K-AKT and TNF signaling pathways.

Key words: Dachaihu Decoction, Network pharmacology, Hyperlipidemia