Investigation on the mechanism of YQHX against cerebral ischemic injury based on network pharmacology and molecular docking

doi:10.5246/jcps.2022.02.010

Abstract

Abstract:

Cerebral ischemia (CI) is the world’s second-largest lethal disease, with a high recurrence and teratogenic rate. Traditional Chinese medicine (TCM) YQHX (a pharmaceutical preparation from herbs) has a certain effect in the clinical treatment of CI, while its underlying mechanism remains largely undetermined. To explore the potential mechanism, we used network pharmacology and molecular docking in the present study. TCMSP and CNKI databases were used to explore the active ingredients of YQHX; the Pharmmapper database was used to get the ingredient targets; the OMIM, GeneCards, and DisGeNET databases were used to obtain the disease targets; the Venn diagram was used to obtain the intersection targets, the Cytoscape was used to visualize results and plug-in MCODE to obtain core targets; the Metascape database was used to perform GO and KEGG pathway enrichment analyses on core targets. The top 20 KEGG pathway enrichment pathways were used to construct the "ingredient-target-pathway" network by Cytoscape; the top 10 ingredients and the top five protein targets were used for molecular docking with AutoDock Vina software, and PyMoL and Ligplus software were used to visualize the results. A total of 83 active ingredients were screened from YQHX. Moreover, 432 corresponding targets, 2005 disease-related targets, and 140 drug-disease intersection targets were obtained. GO biological function and KEGG pathway enrichment analyses yielded 507 biological function entries and 141 signaling pathways. KEGG pathway enrichment was mainly involved in cell proliferation, adhesion, migration, and other processes. Molecular docking results showed that the key ingredients and core targets screened had a strong binding activity, including EGFR, MAP2K1, and KDR. The combination of miltionone I and miltiodiol was relatively stable. The main biological mechanism of YQHX in the treatment of CI might play a role through the signaling pathway related to the tyrosine kinase receptor, which was also the improvement of the theory of "benefiting qi and activating blood circulation for promoting the production of blood and blood vessels".

Key words: Network pharmacology, Molecular docking, YQHX, Cerebral ischemia, Mechanism

Supporting:

Yan Shang, Xiaoyuan Lin, Tiantian Zhang, Lihua Xie, Guoheng Hu. Investigation on the mechanism of YQHX against cerebral ischemic injury based on network pharmacology and molecular docking[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(2): 117-133.

Figures/Tables 14

Table 1. Information of 83 active ingredients in YQHX.

Table 2. Top 10 active ingredients and targets of YQHX.

Table 3. The core target of YQHX cluster 1.

Table 4. Top 20 pathways based on KEGG pathway enrichment analysis.

Table 5. Docking results of YQHX main ingredients with the key target.

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