A bioinformatics investigation into molecular mechanism of Yinzhihuang granules for treating hepatitis B by network pharmacology and molecular docking verification

Abstract

Yinzhihuang granules (YZHG) is a patented Chinese medicine for the treatment of hepatitis B. This study aimed to investigate the intrinsic mechanisms of YZHG in the treatment of hepatitis B and to provide new evidence and insights for its clinical application. The chemical compounds of YZHG were searched in the CNKI and PUBMED databases, and their putative targets were then predicted through a search of the SuperPred and Swiss Target Prediction databases. In addition, the targets of hepatitis B were obtained from TTD, PharmGKB and DisGeNET. The abovementioned data were visualized using Cytoscape 3.7.1, and network construction identified a total of 13 potential targets of YZHG in the treatment of hepatitis B. Molecular docking verification showed that CDK6, CDK2, TP53 and BRCA1 might be strongly correlated with hepatitis B treatment. Furthermore, GO and KEGG analyses indicated that the treatment of hepatitis B by YZHG might be related to positive regulation of transcription, positive regulation of gene expression, the hepatitis B pathway and the viral carcinogenesis pathway. Network pharmacology intuitively shows the multicomponent, multitarget and multichannel pharmacological effects of YZHG in the treatment of hepatitis B and provides a scientific basis for its mechanism of action.

Figure 1

Workflow diagram of the network pharmacology-based analysis of YZHG in the treatment of hepatitis B.

Figure 2

(a) Principal component analysis of chemical compounds of YZHG. (b) Compound-putative target network of YZHG. The light blue color indicates the chemical composition; the red color indicates the composition derived from Huangqin; the purple color indicates the composition derived from Zhizi; the dark blue color indicates the composition derived from Yinchen; the green indicates the composition derived from Jinyinhua; and the blue-green gradient indicates the compounds derived from Yinchen and Jinyinhua [drawn by Cytoscape 3.7.1 (https://www.cytoscape.org/)].

Figure 3

PPI network related to hepatitis B. The orange color indicates primary proteins, and the green color indicates secondary proteins [drawn by Cytoscape 3.7.1 (https://www.cytoscape.org/)].

Figure 4

(a) PPI network related to potential targets. The yellow color indicates primary proteins, and the red color indicates secondary proteins [drawn by Cytoscape 3.7.1 (https://www.cytoscape.org/)]. (b) Venn diagram of protein interactions. (c) Module analysis of the network for the identification of potential targets [drawn by Cytoscape 3.7.1 (https://www.cytoscape.org/)]. (d) The GO and KEGG diagram of module 1 [drawn by R 3.6.3 (https://cran.r-project.org/doc/FAQ/R-FAQ.html#Citing-R)].

Figure 5

KEGG analysis pathway map of potential targets.

Figure 6

Detailed target-compound interactions with the three highest molecular docking affinities.

Figure 7

(a) Herb-compound-target-pathway network. The red squares represent the YZHG; the orange triangles represent the four drugs in the YZHG; the yellow circles represent the ingredients in each drug; the green circles represent the targets corresponding to the ingredients; and the purple hexagons represent the pathways enriched with the targets. (b) Illustration of the crucial biological processes involving putative targets and known therapeutic targets of YZHG: signal transducer and activator of transcription 3, cyclin-dependent kinase 2, transcription factor AP1, cAMP-response element-binding protein, signal transducer and activator of transcription 5, and cellular tumor antigen p53.