Network pharmacology-based study on the mechanism of Yishen-Huashi-Granules in the treatment of chronic glomerulonephritis

doi:10.3877/cma.j.issn.2095-3216.2021.04.001

Abstract

Abstract:

Objective

To explore the effective components, potential targets, pathways, and the mechanism of Yishen-Huashi-Granules in the treatment of chronic glomerulonephritis by means of network pharmacology.

Methods

Through use of the analysis platform of the Traditional Chinese Medicine Systems Pharmacology (TCMSP), a database was established for the active ingredients and targets of the Yishen-Huashi-Granules. Screening of the chronic glomerulonephritis-related genes and targets was performed with the human gene database (GeneCards), the database of Online Mendelian Inheritance in Man (OMIM), the Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB), the Therapeutic Target Database (TTD), and drug action target database (DrugBank). The protein-protein association database (STRING) was used to analyze the protein-protein interaction, and the core genes were obtained from screening of the Protein-Protein Interaction(PPI) network. By use of the Cytoscape software, a "key active ingredient-core target gene" network was constructed. Finally, the gene ontology (GO) database was applied to perform the function enrichment analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used for signal pathway analysis.

Results

The screening found out 258 target genes for active ingredients of traditional Chinese medicine, 2143 target genes for chronic glomerulonephritis, and 132 target genes for active ingredients of Yishen-Huashi-Granules in the treatment of chronic glomerulonephritis. Among these, the core target genes were the proto-oncogene FOS, mitogen-activated protein kinases (MAPK8, MAPK3, MAPK14, MAPK1), and the proto-oncogene JUN, etc. 177 active ingredients of Yishen-Huashi-Granules were related to the treatment of chronic glomerulonephritis. The GO function enrichment analysis indicated that the Yishen-Huashi-Granules were mainly involved in 11 molecular functions and 10 biological processes. The KEGG pathway enrichment analysis showed that the treatment of chronic glomerulonephritis by Yishen-Huashi-Granules mainly involved signal molecules including the advanced glycation end products (AGEs) and the receptor for AGE (RAGE), tumor necrosis factor (TNF), interleukin-17 (IL-17), hypoxia inducible factor-1 (HIF-1), and Toll-like receptors, etc.

Conclusion

Through quercetin, naringenin, kaempferol, baicalein, and other active ingredients, the Yishen-Huashi-Granules could regulate targets as proto-oncogenes, mediate the FOS, MAPK, AGE-RAGE, HIF-1, and other related pathways, and affect the body′s immune regulation, anti-inflammatory, antioxidant, and other processes, playing a role in the treatment of chronic glomerulonephritis. The Yishen-Huashi-Granules′ integral regulation of multi-ingredient, multi-target, and multi-pathway as well as the potential goals may provide a research foundation for the in-depth exploration of the mechanisms and applications in the future.

Key words: Yishen-Huashi-Granules, Chronic glomerulonephritis, Network pharmacology, Targets, Mechanism

Tianxiang Hu, Guirui Huang, Wei Mao, Chuang Li, Peng Xu, Ruimin Tian, Chen Xie. Network pharmacology-based study on the mechanism of Yishen-Huashi-Granules in the treatment of chronic glomerulonephritis[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2021, 10(04): 181-188.

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References 35

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药物	活性成分(个)	成分对应靶基因(个)
人参	22	748
黄芪	20	953
白术	7	774
茯苓	15	121
泽泻	10	165
半夏	13	1 302
羌活	15	1 243
独活	9	650
防风	18	1 931
柴胡	17	2 737
黄连	14	596
白芍	13	990
陈皮	5	479
甘草	92	2 506
生姜	5	2 225
大枣	29	1 329

药物	活性成分(个)	成分对应靶基因(个)
人参	22	748
黄芪	20	953
白术	7	774
茯苓	15	121
泽泻	10	165
半夏	13	1 302
羌活	15	1 243
独活	9	650
防风	18	1 931
柴胡	17	2 737
黄连	14	596
白芍	13	990
陈皮	5	479
甘草	92	2 506
生姜	5	2 225
大枣	29	1 329

名称	有效成分ID	药物成分(英文名称)	药物成分(中文名称)	口服利用吸收度(%)	类药性
甘草	MOL004891	shinpterocarpin		80.30	0.73
	MOL004328	naringenin	柚皮素	59.29	0.21
	MOL000098	quercetin	槲皮素	46.43	0.28
	MOL003896	7-methoxy-2-methyl isoflavone	7-甲氧基-2-甲基异黄酮	42.56	0.20
	MOL000422	kaempferol	山柰酚	41.88	0.24
	MOL000497	licochalcone-A	甘草查耳酮甲	40.79	0.29
黄芪	MOL000378	7-O-methylisomucronulatol		74.69	0.30
	MOL000098	quercetin	槲皮素	46.43	0.28
	MOL000422	kaempferol	山柰酚	41.88	0.24
柴胡	MOL000098	quercetin	槲皮素	46.43	0.28
	MOL000422	kaempferol	山柰酚	41.88	0.24
陈皮	MOL004328	naringenin	柚皮素	59.29	0.21
	MOL005828	nobiletin	川陈皮素	61.67	0.52
白芍	MOL000422	kaempferol	山柰酚	41.88	0.24
半夏	MOL002714	baicalein	黄芩素	33.52	0.21
大枣	MOL000098	quercetin	槲皮素	46.43	0.28
防风	MOL000173	wogonin	汉黄芩素	30.68	0.23
黄连	MOL000098	quercetin	槲皮素	46.43	0.28
人参	MOL000422	kaempferol	山柰酚	41.88	0.24

名称	有效成分ID	药物成分(英文名称)	药物成分(中文名称)	口服利用吸收度(%)	类药性
甘草	MOL004891	shinpterocarpin		80.30	0.73
	MOL004328	naringenin	柚皮素	59.29	0.21
	MOL000098	quercetin	槲皮素	46.43	0.28
	MOL003896	7-methoxy-2-methyl isoflavone	7-甲氧基-2-甲基异黄酮	42.56	0.20
	MOL000422	kaempferol	山柰酚	41.88	0.24
	MOL000497	licochalcone-A	甘草查耳酮甲	40.79	0.29
黄芪	MOL000378	7-O-methylisomucronulatol		74.69	0.30
	MOL000098	quercetin	槲皮素	46.43	0.28
	MOL000422	kaempferol	山柰酚	41.88	0.24
柴胡	MOL000098	quercetin	槲皮素	46.43	0.28
	MOL000422	kaempferol	山柰酚	41.88	0.24
陈皮	MOL004328	naringenin	柚皮素	59.29	0.21
	MOL005828	nobiletin	川陈皮素	61.67	0.52
白芍	MOL000422	kaempferol	山柰酚	41.88	0.24
半夏	MOL002714	baicalein	黄芩素	33.52	0.21
大枣	MOL000098	quercetin	槲皮素	46.43	0.28
防风	MOL000173	wogonin	汉黄芩素	30.68	0.23
黄连	MOL000098	quercetin	槲皮素	46.43	0.28
人参	MOL000422	kaempferol	山柰酚	41.88	0.24

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