Analysis of core functional components in Yinchenhao Decoction and their pathways for treating liver fibrosis

doi:10.12122/j.issn.1673-4254.2024.08.09

Abstract

Abstract:

Objective To analyze the core functional component groups (CFCG) in Yinchenhao Decoction (YCHD) and their possible pathways for treating hepatic fibrosis based on network pharmacology. Methods PPI data were extracted from DisGeNET, Genecards, CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1. The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction. A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets. In cultured human hepatic stellate cells (LX-2 cells), the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay; the effects of these compounds on collagen α1 (Col1a1) mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting. Results A total of 1005 pathogenic genes, 226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained. Benzyl acetate, vanillic acid, clorius, polydatin, lauric acid and ferulic acid were selected for CCK-8 verification, and they all showed minimal cytotoxicity below the concentration of 200 μmol/L. Clorius, polydatin, lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation. At the concentration of 200 μmol/L, all these 4 components inhibited PI3K, p-PI3K, AKT, p-AKT, ERK, p-ERK, P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells. Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate, vanillic acid, clorius, polydatin, lauric acid and ferulic acid, which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

Key words: Yinchenhao Decoction, core functional component groups, network pharmacology, CDR, hepatic fibrosis, LX-2 cells

Xingmei CHEN, Qinwen LIU, Yi LI, Xiaoyu ZHONG, Qiling FAN, Ke MA, Liuting LUO, Daogang GUAN, Zhibo ZHU. Analysis of core functional components in Yinchenhao Decoction and their pathways for treating liver fibrosis[J]. Journal of Southern Medical University, 2024, 44(8): 1508-1517.

Figures/Tables 9

References 30

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Formula/Herbs	Component	Content (mg/g)
Rheum palmatumL.	Catechin	0.015-11.66
	Chrysophanol	0.17-4.36
	(-)-epicatechin	0.98-6.33
	Gallic acid	0.041-4.21
	Isolindleyin	0.056-4.37
	Lindleyin	0.40-4.02
	Phenylbutanone-glucoside	0.36
	Physcion	0.09-0.15
	4,3,5'-trihydroxystilbene-4-(6"-galloyl-glucoside)	0.14-0.20
	Emodin	0.058-4.15
	Rhein	0.08-4.97
	Physcione	0.056-1.66
	Sennoside B	0.47-1.59
	3,4,3',5'-tetrahydroxystilbene-3-glucoside	0.05
	(-)-Epicatechin gallate	0.37-0.045
	(+)-catechin	0.07-0.79
	1,6-digalloyl-2-cinnamoyi-glucose	0.07-0.30
	1-galloyl-2-cinnamoyl-glucose	0.63-1.48
	2-cinnamoyl-glucose	0.13-0.42
	4-4-HydroxyphenylButan-2-One	0.48
	Aloe-emodin-8-glucoside	0.31-0.46
	Chrysophanol-8-glucoside	0.52-1.08
	Emodin-8-glucoside	0.10-1.16
	Epicatechin	0.28-0.70
	Musizin-glucoside	0.06-0.82
	Physcion-8-glucoside	0.20-0.78
	Sennosides	0.40-2.20
	Torachrysone-8-glucoside	0.12-0.25
	Trans-cinnamic acid	1.05
Artemisia capillaris Thunb.	Caffeic acid	0.31
	Chlorogenic acid	0.49-25.09
	P-hydroxyacetophenone	0.03
	Oleanolic acid	4.03
	Rutin	0.045
	Isoquercitrin	0.0094
	4,5-Dicaffeoylquinic acid	0.92
	Hyperin	0.0129
	Isorhamnetin-3-o-glucoside	0.0039
	3, 5-Dicaffeoylquinic acid	4.21
	4,5-O-dicaffeoyl quinic acid	4.55
	Hyperoside	0.52-7.81
Yinchenhao Decoction	Catechin	0.09-1.29
	Chlorogenic acid	0.43-18.12
	Gallic acid	0.58
	Genipin	0.0053
	Geniposide	0.033-23.07
	p-Hydroxyacetophenone	0.69
	Physcion	0.004-1.20
	Quercetin	0.041
	Scoparone	0.15
	Scopoletin	0.0087
	Emodin	0.0083-1.39
	Crocin I	1.38
	Crocin II	0.15
	Rhein	0.15-13.04
	Esculetin	0.024
	Aloe-emodin	0.041-6.26
	Aloe-emodin-8-O-β-D-glucoside	0.20
	Chrysophanol-1-O-β-D-glucoside	0.17
	deacetyl asperulosidic acid methylester	0.67
	Hyperoside	0.065
Gardenia jasminoides Ellis	Chlorogenic acid	0.12-0.27
	Geniposide	2.13-74.65
	Geniposidic acid	1.04-1.99
	Neochlorogenic acid	0.43
	Picrocrocin	1.30
	Crocin I	1.27-19.16
	Crocin II	0.96-1.18
	4-Dicaffeoylquinic Acid	2.14
	Crocin III	0.44
	Deacetyl asperulosidic acid methylester	0.44-3.36
	Genipin 1-gentiobioside	0.56-17.94
	Rutinum	1.03

Formula/Herbs	Component	Content (mg/g)
Rheum palmatumL.	Catechin	0.015-11.66
	Chrysophanol	0.17-4.36
	(-)-epicatechin	0.98-6.33
	Gallic acid	0.041-4.21
	Isolindleyin	0.056-4.37
	Lindleyin	0.40-4.02
	Phenylbutanone-glucoside	0.36
	Physcion	0.09-0.15
	4,3,5'-trihydroxystilbene-4-(6"-galloyl-glucoside)	0.14-0.20
	Emodin	0.058-4.15
	Rhein	0.08-4.97
	Physcione	0.056-1.66
	Sennoside B	0.47-1.59
	3,4,3',5'-tetrahydroxystilbene-3-glucoside	0.05
	(-)-Epicatechin gallate	0.37-0.045
	(+)-catechin	0.07-0.79
	1,6-digalloyl-2-cinnamoyi-glucose	0.07-0.30
	1-galloyl-2-cinnamoyl-glucose	0.63-1.48
	2-cinnamoyl-glucose	0.13-0.42
	4-4-HydroxyphenylButan-2-One	0.48
	Aloe-emodin-8-glucoside	0.31-0.46
	Chrysophanol-8-glucoside	0.52-1.08
	Emodin-8-glucoside	0.10-1.16
	Epicatechin	0.28-0.70
	Musizin-glucoside	0.06-0.82
	Physcion-8-glucoside	0.20-0.78
	Sennosides	0.40-2.20
	Torachrysone-8-glucoside	0.12-0.25
	Trans-cinnamic acid	1.05
Artemisia capillaris Thunb.	Caffeic acid	0.31
	Chlorogenic acid	0.49-25.09
	P-hydroxyacetophenone	0.03
	Oleanolic acid	4.03
	Rutin	0.045
	Isoquercitrin	0.0094
	4,5-Dicaffeoylquinic acid	0.92
	Hyperin	0.0129
	Isorhamnetin-3-o-glucoside	0.0039
	3, 5-Dicaffeoylquinic acid	4.21
	4,5-O-dicaffeoyl quinic acid	4.55
	Hyperoside	0.52-7.81
Yinchenhao Decoction	Catechin	0.09-1.29
	Chlorogenic acid	0.43-18.12
	Gallic acid	0.58
	Genipin	0.0053
	Geniposide	0.033-23.07
	p-Hydroxyacetophenone	0.69
	Physcion	0.004-1.20
	Quercetin	0.041
	Scoparone	0.15
	Scopoletin	0.0087
	Emodin	0.0083-1.39
	Crocin I	1.38
	Crocin II	0.15
	Rhein	0.15-13.04
	Esculetin	0.024
	Aloe-emodin	0.041-6.26
	Aloe-emodin-8-O-β-D-glucoside	0.20
	Chrysophanol-1-O-β-D-glucoside	0.17
	deacetyl asperulosidic acid methylester	0.67
	Hyperoside	0.065
Gardenia jasminoides Ellis	Chlorogenic acid	0.12-0.27
	Geniposide	2.13-74.65
	Geniposidic acid	1.04-1.99
	Neochlorogenic acid	0.43
	Picrocrocin	1.30
	Crocin I	1.27-19.16
	Crocin II	0.96-1.18
	4-Dicaffeoylquinic Acid	2.14
	Crocin III	0.44
	Deacetyl asperulosidic acid methylester	0.44-3.36
	Genipin 1-gentiobioside	0.56-17.94
	Rutinum	1.03

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