Targeting AGE-RAGE Signaling Pathway with Hujin Decoction Ameliorates MAFLD in HepG2 Cells.

PURPOSE

To explore the mechanism and substance basis of HJD for the treatment of MAFLD based on system pharmacology.

PATIENTS AND METHODS

The ingredients of HJD in vitro and in vivo were detected by UPLC-MS/MS, then network pharmacology and molecular docking technology were used to predict the mechanism and substance basis, then the establishment of in vitro MAFLD model was confirmed by oil red O staining and ELISA technology, and finally the mechanism was verified by PCR, WB and flow cell technology.

RESULTS

System pharmacology determined that succinic acid, Ginsenoside Rh4, Caffeic acid, 7-Methoxycoumarin, 5-Acetylsalicylic acid and other ingredients were the basis of pharmacodynamic substances, while RAGE[Advanced glycosylation end product-specific receptor (RAGE)], BCL2[Apoptosis regulator Bcl-2 (BCL2)], and CASP3[Caspase-3 (CASP3)] were predicted as the core targets, and AGE-RAGE was the key pathway. In vitro experiments confirmed that HJD can reduce hepatocyte apoptosis by downregulating the AGE-RAGE signaling pathway to alleviate MAFLD.

CONCLUSION

HJD may act on RAGE, BCL2, CASP3, and other key targets to regulate the AGE-RAGE signaling pathway through succinic acid, Ginsenoside Rh4 and Caffeic acid. This study provides a theoretical basis for the clinical application and quality control of HJD.