Mechanism of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata in Treatment of Acute-on-chronic Liver Failure Based on Bioinformation Analysis and Experimental Validation
10.13422/j.cnki.syfjx.20241615
- VernacularTitle:基于生物信息分析及实验验证探讨赤芍-附子治疗慢加急性肝衰竭的作用机制
- Author:
Xiaoling TIAN
1
;
Yu ZHANG
1
;
Shan DU
1
;
Mengsi WU
1
;
Nianhua TAN
1
;
Bin CHEN
1
Author Information
1. The First Affiliated Hospital of Hunan University of Chinese Medicine， Changsha 410007， China
- Publication Type:Journal Article
- Keywords:
acute-on-chronic liver failure;
Paeoniae Radix Rubra;
Aconiti Lateralis Radix Praeparata;
phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）;
network pharmacology
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(1):156-165
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of action of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata （CSFZ） in the treatment of acute-on-chronic liver failure （ACLF） through network pharmacology， molecular docking， and animal experiments. MethodsNetwork pharmacology was used to identify potential targets and related signaling pathways for the treatment of ACLF with CSFZ. Molecular docking was used to examine the binding activity of the core components with corresponding key targets. An ACLF rat model was established by subcutaneous and tail vein injections of bovine serum albumin combined with lipopolysaccharide （LPS） + D-galactosamine （D-GalN） intraperitoneal injection. A normal control group （NC）， a model group， a CSFZ group （CSFZ， 5.85 g·kg-1）， and a hepatocyte growth-promoting granule group （HGFG， 4.05 g·kg-1） were set up in this study. Pathological changes in rat liver tissue were observed using hematoxylin and eosin （HE） and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interleukin-6 （IL-6）， B-cell lymphoma-2 （Bcl-2）， Caspase-3， and albumin （ALB）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to measure the mRNA and protein expression levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， phosphorylated PI3K （p-PI3K）， and phosphorylated Akt （p-Akt）. ResultsNetwork pharmacology screening identified 49 active ingredients of CSFZ， 103 action targets， and 3 317 targets related to ACLF. Among these， 74 targets overlapped with CSFZ drug targets. Key nodes in the protein-protein interaction （PPI） network included Akt1， tumor necrosis factor （TNF）， IL-6， Bcl-2， and Caspase-3. Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis identified multiple signaling pathways， with the PI3K/Akt signaling pathway being the most frequent. Molecular docking showed that the core components of the drug exhibited good binding activity with the corresponding key targets. Animal experiments confirmed that CSFZ significantly improved liver tissue pathological damage in ACLF rats， reduced the release of inflammatory factors and liver cell apoptosis， and upregulated the expression levels of the PI3K/Akt signaling pathway. ConclusionThrough network pharmacology， molecular docking， and in vivo experiments， this study confirms the effect of CSFZ in reducing liver cell inflammatory damage and inhibiting liver cell apoptosis. The specific mechanism may be related to its involvement in regulating the PI3K/Akt signaling pathway.
