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Updated: Nov 10, 2025
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Cryptotanshinone Ameliorates Doxorubicin-Induced Cardiotoxicity by Targeting Akt-GSK-3β-mPTP Pathway In Vitro
Xiaoping Wang1,2,3, Qianbin Sun2,3,4, Qianqian Jiang2,3
1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
Abstract:
Cardiotoxicity is one of the main side effects of doxorubicin (Dox) treatment. Dox could induce oxidative stress, leading to an opening of the mitochondrial permeability transition pore (mPTP) and apoptosis in cardiomyocytes. Previous studies have shown that Cryptotanshinone (Cts) has potential cardioprotective effects, but its role in Dox-induced cardiotoxicity (DIC) remains unknown. A Dox-stimulated H9C2 cell model was established. The effects of Cts on cell viability, reactive oxygen species (ROS), superoxide ion accumulation, apoptosis and mitochondrial membrane potential (MMP) were evaluated. Expressions of proteins in Akt-GSK-3β pathway were detected by Western blot. An Akt inhibitor was applied to investigate the effects of Cts on the Akt-GSK-3β pathway. The effects of Cts on the binding of p-GSK-3β to ANT and the formation of the ANT-CypD complex were explored by immunoprecipitation assay. The results showed that Cts could increase cell viability, reduce ROS levels, inhibit apoptosis and protect mitochondrial membrane integrity. Cts increased phosphorylated levels of Akt and GSK-3β. After cells were co-treated with an Akt inhibitor, the effects of Cts were abolished. An immunoprecipitation assay showed that Cts significantly increased GSK-3β-ANT interaction and attenuated Dox-induced formation of the ANT-CypD complex, thereby inhibiting opening of the mPTP. In conclusion, Cts could ameliorate oxidative stress and apoptosis via the Akt-GSK-3β-mPTP pathway.
Insights
Cryptotanshinone (Cts) protects heart cells from doxorubicin (Dox) damage by reducing oxidative stress and apoptosis. It works by activating the Akt-GSK-3β pathway, which prevents mitochondrial dysfunction and cell death.
Area of Science:
- Biochemistry
- Cardiology
- Pharmacology
Background:
- Doxorubicin (Dox) treatment can cause cardiotoxicity, a major side effect.
- Dox-induced cardiotoxicity involves oxidative stress, mitochondrial permeability transition pore (mPTP) opening, and apoptosis in cardiomyocytes.
- The cardioprotective potential of Cryptotanshinone (Cts) against Dox-induced cardiotoxicity (DIC) is not well understood.
Purpose of the Study:
- To investigate the protective effects of Cts against Dox-induced cardiotoxicity in a cellular model.
- To elucidate the underlying molecular mechanisms, focusing on the Akt-GSK-3β pathway and mPTP regulation.
Main Methods:
- Established a Dox-stimulated H9C2 cell model to evaluate Cts effects.
- Assessed cell viability, reactive oxygen species (ROS), apoptosis, and mitochondrial membrane potential (MMP).
- Utilized Western blot to analyze Akt-GSK-3β pathway protein expression and immunoprecipitation assays to study protein interactions.
Main Results:
- Cts significantly improved cell viability, reduced ROS levels, inhibited apoptosis, and preserved MMP.
- Cts treatment increased phosphorylated levels of Akt and GSK-3β.
- Cts enhanced GSK-3β-ANT interaction and reduced ANT-CypD complex formation, thereby inhibiting mPTP opening.
Conclusions:
- Cts demonstrates significant cardioprotective effects against Dox-induced cardiotoxicity.
- These protective effects are mediated through the Akt-GSK-3β pathway, which regulates mPTP opening and subsequent apoptosis.
- Cts ameliorates oxidative stress and apoptosis by modulating the Akt-GSK-3β-mPTP signaling axis.
