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Multi-Omics Reveals Active Components and Mechanisms of Heat-Processed Gypenosides Hepatoprotective Against APAP
Peng Xie1, Qiuru Li1, Shu Jiang1
1Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Changzhi 046000, Shanxi, China.
Biomolecules
|November 27, 2025
Summary
Heat-processed Gynostemma pentaphyllum saponins (HGyp) protect the liver from acetaminophen-induced injury. HGyp reduces liver damage by targeting multiple pathways, including inflammation and apoptosis.
Area of Science:
- Pharmacology
- Hepatology
- Traditional Chinese Medicine
Background:
- Acetaminophen (APAP) overdose is a leading cause of acute liver injury.
- Gynostemma pentaphyllum (HP) saponins are known for their potential therapeutic benefits.
- Understanding the precise mechanisms of HP saponins in liver protection is crucial.
Purpose of the Study:
- To elucidate the hepatoprotective mechanisms of heat-processed Gynostemma pentaphyllum saponins (HGyp) against APAP-induced liver injury.
- To identify key bioactive compounds and molecular targets of HGyp.
- To explore the metabolic pathways involved in HGyp's therapeutic effects.
Main Methods:
- Serum pharmacochemistry and UPLC-MS for compound identification.
- Network pharmacology and molecular docking for target prediction.
- Metabolomics to analyze pathway alterations.
- Biochemical assays and histopathology for liver damage assessment.
- Western blotting to validate protein expression changes.
Main Results:
- HGyp significantly mitigated APAP-induced liver damage in mice.
- 38 bioactive compounds were identified, including prototype saponins and metabolites.
- Key compounds like damulin A/B and gypenosides targeted proteins such as GRB2, STAT3, and HSP90A.
- Metabolomics revealed HGyp's role in PPAR, ferroptosis, and TRP channel regulation.
- HGyp downregulated hepatic HSP90A and STAT3 expression.
Conclusions:
- HGyp exerts multi-target hepatoprotective effects against APAP-induced liver injury.
- Mechanisms involve anti-inflammatory activity, apoptosis regulation, and metabolic pathway modulation.
- This study provides a scientific basis for the use of Gynostemma pentaphyllum in traditional and ethnomedicine for liver protection.
