Exploring Mechanism of Pomegranate Peel on Non-alcoholic Steatohepatitis Based on Network Pharmacology and Experimental Verification
10.13748/j.cnki.issn1007-7693.20223506
- VernacularTitle:基于网络药理学和实验验证探讨石榴皮对非酒精性脂肪性肝炎的作用机制
- Author:
SUN Yi
1
;
HUANG Xinyu
1
;
QU Yaqin
1
;
ZHENG Guohua
1
,
2
;
TIAN Xianxiang
1
;
QIU Zhenpeng
1
Author Information
1. School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China
2. Key Laboratory of Chinese Medicine Resource and Compound Prescription, Hubei University of Chinese Medicine, Wuhan 430065, China
- Publication Type:Journal Article
- Keywords:
pomegranate peel;
network pharmacology;
non-alcoholic steatohepatitis;
cell experiments;
molecular mechanism
- From:
Chinese Journal of Modern Applied Pharmacy
2023;40(17):2384-2392
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the mechanism of pomegranate peel in improving non-alcoholic steatohepatitis (NASH) based on network pharmacology and cell experiments verification. METHODS Using the Traditional Chinese Medicine System Pharmacology Database(TCMSP) to obtain the active components of pomegranate peel and their corresponding targets. NASH-related disease targets were obtained from five disease databases, including the Human Gene Database(GeneCards), etc. To screen the targets of pomegranate peel and NASH and obtain the common targets through Venn diagrams. The protein-protein interaction network of pomegranate peel-NASH was constructed using the protein interaction database(STRING), and the “pomegranate peel-component-target-NASH” network was established with Cytoscape 3.7.1. Gene ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed using Metascape software. Finally, the effect of the main active components in pomegranate peel on NASH was observed with human hepatoma cells(HepG2). RESULTS There were 7 active ingredients in pomegranate peel, 191 target genes, 1 818 NASH targets, and 98 intersection targets. Topological analysis showed that the core components of pomegranate peel in the treatment of NASH were quercetin, kaempferol, and luteolin, and the core targets were protein kinase B(Akt1), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor(TNF). KEGG pathway analysis predicted that pomegranate peel treatment of NASH mainly involved phosphatidylinositol-3-kinase(PI3K)/Akt, nuclear factor kappa B(NF-κB), and other signaling pathways. The results of in vitro cell experiments showed that the expression levels of phosphorylated protein kinase B(p-Akt), IL-6 and other proteins were elevated in the model group compared with the control group(P<0.05). Compared with the model group, the active ingredients of pomegranate peel could significantly reduce the expression level of p-Akt and IL-6(P<0.05), as well as the mRNA expression level of IL-6 and TNF-α(P<0.05). CONCLUSION Pomegranate peel can exert anti-NASH effects through multiple components, multiple targets, and multiple pathways. The mechanism may be related to the active components quercetin, kaempferol, and luteolin in pomegranate peel affecting core targets such as Akt1 and regulating PI3K/Akt, NF-κB, and other signaling pathways, thereby inhibiting the expression of related inflammatory factors.
