Mechanism of Zexie Decoction against liver injury in rats with hyperlipidemic acute pancreatitis based on network pharmacology.
10.19540/j.cnki.cjcmm.20250409.301
- Author:
Tian-Tian TANG
1
;
Rong-Zhan ZHANG
1
;
Fang HUANG
1
;
Lu-Zhou XU
2
;
Jia ZHOU
1
Author Information
1. School of Traditional Chinese Pharmacy, China Pharmaceutical University Nanjing 211198, China.
2. Gastroenterology Department, Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing 210004, China.
- Publication Type:Journal Article
- Keywords:
PI3K/AKT signaling pathway;
Zexie Decoction;
autophagy;
endoplasmic reticulum stress;
hyperlipidemic acute pancreatitis;
liver injury;
network pharmacology;
oxidative stress
- MeSH:
Animals;
Rats, Sprague-Dawley;
Drugs, Chinese Herbal/administration & dosage*;
Network Pharmacology;
Rats;
Pancreatitis/genetics*;
Hyperlipidemias/genetics*;
Male;
Liver/injuries*;
Protein Interaction Maps/drug effects*;
Signal Transduction/drug effects*;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*;
Interleukin-1beta/genetics*;
Humans
- From:
China Journal of Chinese Materia Medica
2025;50(15):4352-4362
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to investigate the effect and underlying mechanisms of Zexie Decoction against liver injury in rats with hyperlipidemic acute pancreatitis(HLAP). The network pharmacology-related databases were used to screen the active components and potential targets of Zexie Decoction, as well as the disease targets of HLAP. A protein-protein interaction(PPI) network of the overlapping targets was constructed. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis and Gene Ontology(GO) functional enrichment analysis were performed on the overlapping targets. Sprague-Dawley(SD) rats were randomly divided into sham group, model group, low-dose Zexie Decoction group, and high-dose Zexie Decoction group. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect serum biochemical indicators. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of the pancreas and liver tissues, while oil red O staining was employed to assess hepatic steatosis. Immunofluorescence staining was used to detect the expression of IL-1β and NLRP3 in pancreatic tissues. Western blot analysis was conducted to evaluate the expression levels of proteins related to oxidative stress, endoplasmic reticulum stress, the PI3K/AKT signaling pathway, and autophagy. Network pharmacology predictions identified 721 targets of Zexie Decoction and 2 486 targets associated with HLAP, with 279 overlapping targets. GO enrichment analysis yielded 1 112 entries, and KEGG enrichment analysis identified 179 signaling pathways. Experimental results showed that Zexie Decoction could reduce the levels of lipid metabolites, serum enzymes, and inflammatory cytokines in HLAP rats, alleviate pathological damage to the pancreas and liver, decrease hepatic lipid accumulation, and decrease the expression of IL-1β and NLRP3 in pancreatic tissues. In addition, Zexie Decoction significantly upregulated the expression of antioxidant stress-related proteins NRF2 and HO-1, downregulated the expression of endoplasmic reticulum stress-related proteins BiP, xBP1s, p-eIF2α, eIF2α, and ATF4, inhibited the expression of PI3K and phosphorylation of AKT, increased the expression of autophagy-related proteins Beclin1, ATG3, ATG5, and ATG12, and reduced the expression of p62. In conclusion, Zexie Decoction can improve HLAP, and its mechanism may be associated with alleviating oxidative stress and endoplasmic reticulum stress, inhibiting the PI3K/AKT pathway, and inducing autophagy in hepatocytes.
