阔叶十大功劳抗炎作用机制的实验研究及网络药理学分析

doi:10.3976/j.issn.1002-4026.20230043

Abstract

Abstract:

The aim of this study was to investigate the active ingredients and mechanism of action of the anti-inflammatory effect of Mahonia bealei (Fort.) Carr. in Hmong medicine based on network pharmacology and animal experiments. Inflammation models of mice and rats were generated using xylene and carrageenan gum, respectively, and Mahonia bealei (Fort.) Carr. was gavaged (dose of 1.950 mg/kg for mice; 1.350 mg/kg for rats). The active ingredients and their corresponding targets of Mahonia bealei (Fort.) Carr. were obtained using TCMSP, SymMap, SwisstargetPrediction, SEA, and STICH, among other databases, with oral bioavailability ≥30% and drug-likeness ≥0.18. Inflammationrelated targets were obtained through GeneCards, DisGeNET, TTD, DrugBank, OMIM and other databases. The intersection targets of diseases and drugs were determined using Venny 2.1.0, and 10 hub gene were obtained through Cytoscape's MCODE, CytoHubba plug-in and constructed drug-component-target network diagram; Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) enrichment analysis and molecular docking were performed for the 10 Hub gene. The results of animal experiments showed that Mahonia bealei (Fort.) Carr. could be used to reduce the inflammatory symptoms in mice and rats. The network pharmacological analysis revealed 28 Mahonia bealei (Fort.) Carr. active ingredients, 753 drug action targets, 1 025 inflammatory targets, 225 Mahonia bealei (Fort.) Carr. inflammatory crossover targets and 10 hub genes. The results of GO and KEGG enrichment analysis showed that Mahonia bealei (Fort.) Carr. top ten utilities were predominantly involved in the JAK-STAT signaling pathway, Th17 cell differentiation and some cancer pathways. The molecular docking results demonstrated that 11 active ingredients, including berberine and isoboridine, were successfully docked with 8 targets, including JUN and JAK3. The results of animal experiments showed that Mahonia bealei (Fort.) Carr. has anti-inflammatory effects, and the main ingredients of anti-inflammation include quercetin and berberine, among other compounds, and the mechanism of anti-inflammation may be through the action onIL-2, JAK1 and other targets, involved in JAK-STAT signaling pathway, Th17 cell differentiation, and other pathways of anti-inflammation. The present study initially revealed the material basis and mechanism of action of the anti-inflammatory effect of Mahonia bealei (Fort.) Carr.

Key words: Mahonia bealei (Fort.) Carr., network pharmacology, inflammation, molecular mechanism, active ingredient

CLC Number:

R285

FU Zhaoju, CHENG Guo, LIN Dengmei, LI Jun, ZHANG Nannan. Experimental study and network pharmacological analysis of the anti-inflammatory action mechanism of Mahonia bealei (Fort.) Carr.[J].Shandong Science, 2024, 37(1): 24-31.

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References 25

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Tukey的多重比较试验	平均差异	95.00% CI of diff	Summary	P值
空白组vs.阳性组	0.416 5	0.143 4~0.689 5	**	0.003 4
空白组vs.实验组	0.418 8	0.145 8~0.691 9	**	0.003 2
阳性组vs.实验组	0.002 338	-0.270 7~0.275 4	ns	0.999 7

Tukey的多重比较试验	平均差异	95.00% CI of diff	Summary	P值
空白组vs.阳性组	0.336 9	0.131 5~0.542 2	**	0.001 9
空白组vs.实验组	0.230 1	0.024 81~0.435 5	*	0.027 3
阳性组vs.实验组	-0.106 7	-0.312 0~0.098 61	ns	0.390 8

药物ID	成分名称	OB值/%	DL值
MOL005107	乙氧基白屈菜红素(Ethoxychelerythrine)	62.21	0.88
MOL001458	黄连碱(Coptisine)	30.67	0.86
MOL001454	小檗碱(Berberine)	36.86	0.78
MOL001987	β-谷甾醇(β-Sitosterol)	33.94	0.70
MOL000785	黄藤素(Palmatine)	64.60	0.65
MOL004763	异博尔定(Isoboldine)	39.53	0.37
MOL004093	硫唑胺(Azaleatin)	54.28	0.30
MOL000098	槲皮素(Quercetin)	46.43	0.28
MOL008099	鸦胆子苷M(Yadanzioside M)	45.04	0.23
MOL001495	亚麻酸乙酯(Ethyl linolenate)	46.10	0.20

蛋白名称	成分名称	LibDock得分
SRC	小檗碱(Berberine)	105.047
MAPK1	不列颠宁(Britanin)	105.331
MAPK14	不列颠宁(Britanin)	112.545
MAPK14	小檗碱(Berberine)	107.844
JAK1	不列颠宁(Britanin)	101.951
EGFR	弗拉辛(Flazin)	111.153
JAK3	异博尔定(Isoboldine)	133.000
IL2	硫唑胺(Azaleatin)	120.744
IL2	异鼠李素(Isorhamnetin)	119.912
JUN	鸦胆子苷H(Yadanzioside H)	138.656
JUN	鸦胆子苷J(Yadanzioside J)	116.164

Experimental study and network pharmacological analysis of the anti-inflammatory action mechanism of Mahonia bealei (Fort.) Carr.

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