# Multi-Omics Reveals Active Components and Mechanisms of Heat-Processed Gypenosides Hepatoprotective Against APAP Injury

## TL;DR

This study identifies the active components and mechanisms of heat-processed Gypenosides in protecting the liver from APAP-induced injury using multi-omics approaches.

## Contribution

The study reveals key bioactive compounds and molecular pathways involved in the hepatoprotective effects of heat-processed Gypenosides.

## Key findings

- HGyp significantly reduced liver damage in mice as shown by biochemical and histopathological analyses.
- 38 bioactive compounds were identified, including 16 saponins and 11 metabolites.
- HGyp targets multiple pathways, including PPAR, ferroptosis, and inflammatory mediator regulation of TRP channels.

## Abstract

This study elucidates the hepatoprotective mechanisms of heat-processed Gynostemma pentaphyllum (Thunb.) Makino saponins (HGyp) against APAP-induced liver injury using serum pharmacochemistry, metabolomics, and network pharmacology. HGyp significantly mitigated liver damage in mice, as confirmed by biochemical and histopathological analyses. UPLC-MS identified 38 bioactive compounds, including 16 prototype saponins and 11 metabolites. Network pharmacology and molecular docking revealed damulin A/B, gypenosides (L/LI/LVI/XLVI), and ginsenosides (Rg3/Rd) as key components targeting GRB2, FGF2, MMP2, STAT3, CASP3, and HSP90A. Western blotting confirmed the HGyp-mediated downregulation of hepatic HSP90A and STAT3. Metabolomics identified four critical pathways, PPAR, ferroptosis, and the inflammatory mediator regulation of TRP channels involved in hepatoprotection. HGyp exerts multi-target effects via anti-inflammatory activity, apoptosis, and metabolism, providing a framework for Chinese medicine and ethnomedicine research.