Related Experiment Video
Updated: Aug 14, 2025
Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
Published on: January 10, 2025
Ginsenoside F1 attenuates pirarubicin-induced cardiotoxicity by modulating Nrf2 and AKT/Bcl-2 signaling pathways
Yang Zhang1,2, Jiulong Ma1, Shan Liu1
1Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Jilin, China.
Background:
Pirarubicin (THP) is an anthracycline antibiotic used to treat various malignancies in humans. The clinical usefulness of THP is unfortunately limited by its dose-related cardiotoxicity. Ginsenoside F1 (GF1) is a metabolite formed when the ginsenosides Re and Rg1 are hydrolyzed. However, the protective effects and underlying mechanisms of GF1 on THP-induced cardiotoxicity remain unclear.
Methods:
We investigated the anti-apoptotic and anti-oxidative stress effects of GF1 on an in vitro model, using H9c2 cells stimulated by THP, plus trigonelline or AKT inhibitor imidazoquinoxaline (IMQ), as well as an in vivo model using THP-induced cardiotoxicity in rats. Using an enzyme-linked immunosorbent test, the levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (c-TnT), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione (GSH) were determined. Nuclear factor (erythroid-derived2)-like 2 (Nrf2) and the expression of Nrf2 target genes, including heme oxygenase-1 (HO-1), glutathione-S-transferase (Gst), glutamate-cysteine ligase modifier subunit (GCLM), and expression levels of AKT/Bcl-2 signaling pathway proteins were detected using Western blot analysis.
Results:
THP-induced myocardial histopathological damage, electrocardiogram (ECG) abnormalities, and cardiac dysfunction were reduced in vivo by GF1. GF1 also decreased MDA, BNP, CK-MB, c-TnT, and LDH levels in the serum, while raising SOD and GSH levels. GF1 boosted Nrf2 nuclear translocation and Nrf2 target gene expression, including HO-1, Gst, and GCLM. Furthermore, GF1 regulated apoptosis by activating AKT/Bcl-2 signaling pathways. Employing Nrf2 inhibitor trigonelline and AKT inhibitor IMQ revealed that GF1 lacked antioxidant and anti-apoptotic effects.
Conclusion:
In conclusion, GF1 was found to alleviate THP-induced cardiotoxicity via modulating Nrf2 and AKT/Bcl-2 signaling pathways, ultimately alleviating myocardial oxidative stress and apoptosis.
Insights
Ginsenoside F1 (GF1) protects against pirarubicin (THP)-induced cardiotoxicity by reducing oxidative stress and apoptosis. GF1 modulates Nrf2 and AKT/Bcl-2 signaling pathways, offering a potential therapeutic strategy against chemotherapy-induced heart damage.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Pirarubicin (THP) is an anthracycline antibiotic used in cancer treatment.
- THP's clinical utility is limited by dose-dependent cardiotoxicity.
- Ginsenoside F1 (GF1), a ginsenoside metabolite, has potential protective effects against THP-induced cardiotoxicity, but its mechanisms are unclear.
Purpose of the Study:
- To investigate the protective effects of GF1 against THP-induced cardiotoxicity.
- To elucidate the underlying mechanisms of GF1's cardioprotective action, focusing on oxidative stress and apoptosis.
- To evaluate GF1's efficacy in both in vitro and in vivo models.
Main Methods:
- In vitro studies used H9c2 cells exposed to THP, with or without GF1, trigonelline, or AKT inhibitor IMQ.
- In vivo studies utilized a rat model of THP-induced cardiotoxicity.
- Biochemical markers (MDA, BNP, CK-MB, c-TnT, LDH, SOD, GSH) and protein expression (Nrf2, HO-1, Gst, GCLM, AKT, Bcl-2) were analyzed.
Main Results:
- GF1 treatment attenuated THP-induced myocardial histopathological damage, ECG abnormalities, and cardiac dysfunction in vivo.
- GF1 reduced serum levels of MDA, BNP, CK-MB, c-TnT, and LDH, while increasing SOD and GSH.
- GF1 promoted Nrf2 nuclear translocation and target gene expression, activated AKT/Bcl-2 signaling, and inhibited apoptosis. Nrf2 and AKT inhibition abolished GF1's effects.
Conclusions:
- GF1 alleviates THP-induced cardiotoxicity by mitigating myocardial oxidative stress and apoptosis.
- The protective mechanisms involve the modulation of Nrf2 and AKT/Bcl-2 signaling pathways.
- GF1 demonstrates potential as a therapeutic agent to prevent or treat chemotherapy-induced cardiotoxicity.
More Related Videos
08:03Hybrid Cell Analysis System to Assess Structural and Contractile Changes of Human iPSC-Derived Cardiomyocytes for Preclinical Cardiac Risk Evaluation
Published on: October 20, 2022
07:15Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:26Heart Failure Drugs: Inotropic Agents
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...