Study on mechanism of iridoid glycosides derivatives from Fructus Gardeniae in treatment of hepatic encephalopathy by network pharmacology and molecular docking technology.

BACKGROUND

This study aims to explore the mechanism of the iridoid glycosides from Fructus Gardeniae (IGFG) in treating hepatic encephalopathy (HE) by combining network pharmacology and molecular docking technology.

METHODS

Firstly, we collected the targets of IGFG and HE. The targets of IGFG were predicted through the CTD, SWISS and TCMSP database and the targets of HE were screened through the DisGeNET database. Then the targets of IGFG and HE were mapped to attain the common target of IGFG in treating HE. Then, chemicals-target-disease network was constructed. Secondly, we constructed protein-protein interactions (PPI) network using STRING database and Cytoscape software. Moreover, we screened the core targets according to the degree value. Thirdly, the mechanism of IGFG in treating HE was revealed by Gene ontology and KEGG enrichment analysis. Meanwhile, chemicals-target-pathway network was constructed. Finally, to further verify the analysis results, molecular docking study was conducted.

RESULTS

Network pharmacology indicates that there are 12 common targets between IGFG and HE. Eleven core targets were identified by the construction of PPI network. Association for core targets, and related pathways was analyzed, implying that core targets related to these pathways are AKT1, tumor necrosis factor, MTOR, CHUK, PPP2CA, IKBKB, AKT2, IKBKG, IL1B, NFKBIA, and CASP8. The main mechanism of IGFG in treating HE is closely related to inhibit inflammatory reaction, regulate immunity, promote hepatocyte regeneration, reduce hepatocyte apoptosis, maintain liver function homeostasis and antiviral function. Finally, the results of molecular docking showed that the binding free energy of geniposide with the core target was less than -5 kJ/mol, which indicated that geniposide could spontaneously bind to the receptor protein and had strong binding force.

CONCLUSION

IGFG can achieve simultaneous intervention of HE by inhibit inflammatory reaction, regulate immunity, promote hepatocyte regeneration, reduce hepatocyte apoptosis, maintain liver function homeostasis and antiviral function. It presents the network regulation mechanism of mutual influence and complex correlation. This study provides a scientific basis for IGFG in the treatment of patients with HE.