Network pharmacology and experimental validation of effects of total saponins extracted from Abrus cantoniensis Hance on acetaminophen-induced liver injury

J Ethnopharmacol. 2024 Apr 24:324:117740. doi: 10.1016/j.jep.2024.117740. Epub 2024 Jan 12.

Abstract

Ethnopharmacological relevance: Abrus cantoniensis Hance (AC), an abrus cantoniensis herb, is a Chinese medicinal herb used for the treatment of hepatitis. Total saponins extracted from AC (ACS) are a compound of triterpenoid saponins, which have protective properties against both chemical and immunological liver injuries. Nevertheless, ACS has not been proven to have an influence on drug-induced liver injury (DILI).

Aim of the study: This study used network pharmacology and experiments to investigate the effects of ACS on acetaminophen (APAP)-induced liver injury.

Materials and methods: The targets associated with ACS and DILI were obtained from online databases. Cytoscape software was utilized to construct a "compound-target" network. In addition, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to analyze the related signaling pathways impacted by ACS. AutoDock Vina was utilized to evaluate the binding affinity between bioactive compounds and the key targets. To validate the findings of network pharmacology, in vitro and in vivo experiments were conducted. Cell viability assay, transaminase activity detection, immunofluorescence assay, immunohistochemistry staining, RT-qPCR, and western blotting were utilized to explore the effects of ACS.

Results: 25 active compounds and 217 targets of ACS were screened, of which 94 common targets were considered as potential targets for ACS treating APAP-induced liver injury. GO and KEGG analyses showed that the effects of ACS exert their effects on liver injury through suppressing inflammatory response, oxidative stress, and apoptosis. Molecular docking results demonstrated that core active compounds of ACS were successfully docked to core targets such as CASP3, BCL2L1, MAPK8, MAPK14, PTGS2, and NOS2. In vitro experiments showed that ACS effectively attenuated APAP-induced damage through suppressing transaminase activity and attenuating apoptosis. Furthermore, in vivo studies demonstrated that ACS alleviated pathological changes in APAP-treated mice and attenuated inflammatory response. Additionally, ACS downregulated the expression of iNOS, COX2, and Caspase-3, and upregulated the expression of Bcl-2. ACS also suppressed the MAPK signaling pathway.

Conclusions: This study demonstrated that ACS is a hepatoprotective drug through the combination of network pharmacology and in vitro and in vivo experiments. The findings reveal that ACS effectively attenuate APAP-induced oxidative stress, apoptosis, and inflammation through inhibiting the MAPK signaling pathway. Consequently, this research offers novel evidence supporting the potential preventive efficacy of ACS.

Keywords: Abrus cantoniensis; Acetaminophen-induced liver injury; Experimental validation; Network pharmacology; Total saponins.

MeSH terms

  • Abrus*
  • Acetaminophen / toxicity
  • Animals
  • Chemical and Drug Induced Liver Injury* / drug therapy
  • Chemical and Drug Induced Liver Injury* / prevention & control
  • Chemical and Drug Induced Liver Injury, Chronic*
  • Drugs, Chinese Herbal*
  • Mice
  • Molecular Docking Simulation
  • Network Pharmacology
  • Transaminases

Substances

  • Acetaminophen
  • Transaminases
  • Drugs, Chinese Herbal