Abstract:

In the present study, we aimed to study the action mechanism of Mongolian medicine Herba Lomatognii on acute liver injury (ALI) using network pharmacology and bioinformatics methods to provide a reference for further study of Herba Lomatognii on metabolic diseases. Herba Lomatognii showed protective effects on D-GlaN-induced ALI model rats, which were used to analyze serum transaminase and enzyme-linked immunosorbent assay changes. The chemical constituents of Herba Lomatognii and their corresponding targets were collected by TCMSP database and literature search. ALI targets were compiled by GenCards and DisGeNet disease databases, and the targets of active constituents of Herba Lomatognii were interesting ALI targets. The obtained targets were targets of Herba Lomatognii against ALI. The Metascape database was used to do a Go function and KEGG pathway enrichment analysis of consensus targets, and Cytoscape software was used to create a correlation network diagram. Validation of molecular docking was carried out by analyzing important core components and significant targets. In addition, Western blotting analysis was utilized to detect transcription activator 3 (STAT3), AKT1, and CASP3 expressions in the rat liver. Serum transaminases and enzyme-linked immunostaining assay demonstrated that Herba Lomatognii had preventive and anti-inflammatory effects on D-GlaN-induced ALI in rats. From network pharmacology screening, a total of 10 active ingredients of Herba Lomatognii and 289 corresponding targets were identified, 843 targets of ALI and 89 targets of both, and GO enrichment and KEGG pathway analysis revealed that the common targets were mostly related to cancer, PI3K-Akt signaling pathway, Ras signaling pathway, HIF-1 signaling pathway, TNF-α signaling pathway, toll-like receptor signaling pathway, MAPK signaling pathway, VEGF signaling pathway, p53 signaling pathway, and NF-κB signaling pathway. Molecular docking results showed that the core components, such as swetiamain, luteolin, and kaempferol, could dock well with the targets of EGFR, SRC, AKT1, STAT3, and CASP3. The expressions of AKT1, STAT3, and CASP3 proteins in the liver tissues of model rats were considerably higher compared with the normal control rats based on Western blotting data (P < 0.05). In contrast to the model group, the AKT1 and STAT3 protein expressions in the liver tissues of the positive group and the Herba Lomatognii low-, medium-, and high-dose groups were significantly decreased (P < 0.05). Compared with the model group, the CASP3 protein expression in the liver tissue of the middle- and high-dosage groups of Herba Lomatognii was significantly lower, and no significant difference was observed in the liver tissue of the low-dosage group of Herba Lomatognii (P > 0.05). Herba Lomatognii contained potential therapeutic agents for ALI and could interfere with the development of ALI through multi-target and multi-pathway approaches.

Key words: Herb Lomatognii, Acute liver injury, Network pharmacology, Molecular docking, Western blotting