Related Experiment Video
Updated: Aug 28, 2025
A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
Published on: June 7, 2018
Tanshinone I inhibits doxorubicin-induced cardiotoxicity by regulating Nrf2 signaling pathway
Qianqian Jiang1, Xu Chen2, Xue Tian1
1School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.
Background:
Doxorubicin (DOX) is a powerful anti-tumor anthracycline drug. However, its clinical use is limited due to the side effect of cardiotoxicity. Tanshinone I (Tan I) is one of the major tanshinones isolated from Salvia miltiorrhiza. Studies have shown that Tan I is effective in the treatment of cardiovascular diseases. However, the potential effects of Tan I against DOX-induced cardiotoxicity (DIC) have yet to be explored.
Purpose:
This study aimed to explore whether Tan I can protect against DIC and to reveal whether Tan I can exert anti-oxidative effect by regulating nuclear erythroid factor 2-related factor 2 (Nrf2) pathway.
Methods:
DIC models were established in vivo by intravenous injection of DOX. Echocardiography was used to monitor the cardiac function of mice. Transmission electron microscopy was used to assess mitochondrial damage. Oxidative stress was measured by dihydroethidium (DHE) staining and western blotting. The accumulation and nuclear translocation of Nrf2 was detected by immunofluorescence. H9C2 cellular DIC model was established in vitro to explore the pharmacological mechanism. Nrf2 small interfering (si)-RNA was applied to H9C2 cells to explore whether Tan I exerted protective effect against DIC through Nrf2 signaling pathway. The protective effects of Tan I on mitochondrial function and mitochondrial membrane permeability were measured by MitoSOX™ Red and JC-1 staining assays, respectively.
Results:
In vivo experiments revealed that Tan I could improve cardiac function and protect against DOX-induced myocardial structural damages in mice models. The oxidative stress induced by DOX was suppressed and apoptosis was mitigated by Tan I treatment. Tan I protected against DOX-induced mitochondrial structural damage. Meanwhile, key proteins in Nrf2 pathways were upregulated by Tan I treatment. In vitro studies showed that Tan I attenuated DOX-induced generation of reactive oxygen species (ROS) in cultured H9C2 cells, reduced apoptotic rates, protected mitochondrial functions and up-regulated Nrf2 signaling pathway. Tan I promoted accumulation and nuclear translocation of Nrf2 protein. In addition, interference of Nrf2 abrogated the anti-oxidative effects of Tan I and reversed the expressions of key proteins in Nrf2 pathway. The protective effects of Tan I on mitochondrial integrity was also mitigated by Nrf2 interference.
Conclusion:
Tan I could reduce oxidative stress and protect against DIC through regulating Nrf2 signaling pathway. Nrf2 is a potential target and Tan I is a novel candidate agent for the treatment of DIC.
Insights
Tanshinone I (Tan I) protects against doxorubicin-induced cardiotoxicity by reducing oxidative stress and improving cardiac function. This protective effect is mediated through the nuclear erythroid factor 2-related factor 2 (Nrf2) signaling pathway.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Toxicology
Background:
- Doxorubicin (DOX) is a potent anti-tumor drug, but its use is limited by cardiotoxicity.
- Tanshinone I (Tan I), derived from Salvia miltiorrhiza, shows promise in treating cardiovascular diseases.
- The protective effects of Tan I against DOX-induced cardiotoxicity (DIC) remain largely unexplored.
Purpose of the Study:
- To investigate the protective potential of Tan I against DIC.
- To determine if Tan I exerts its effects by modulating the nuclear erythroid factor 2-related factor 2 (Nrf2) pathway.
- To elucidate the underlying anti-oxidative mechanisms.
Main Methods:
- Establishment of in vivo (mice) and in vitro (H9C2 cells) models of DIC.
- Assessment of cardiac function using echocardiography and mitochondrial damage via transmission electron microscopy.
- Measurement of oxidative stress (DHE staining, western blotting) and Nrf2 pathway activation (immunofluorescence, western blotting).
- Investigation of Tan I's mechanism using Nrf2 small interfering RNA (siRNA).
Main Results:
- Tan I significantly improved cardiac function and alleviated myocardial structural damage in vivo.
- Tan I suppressed DOX-induced oxidative stress, reduced apoptosis, and protected mitochondrial integrity.
- In vitro, Tan I attenuated reactive oxygen species (ROS) generation, protected mitochondrial function, and upregulated the Nrf2 pathway.
- Nrf2 interference abolished Tan I's anti-oxidative effects and protective actions on mitochondria.
Conclusions:
- Tan I demonstrates significant protective effects against DOX-induced cardiotoxicity.
- The mechanism involves the regulation of the Nrf2 signaling pathway and reduction of oxidative stress.
- Tan I represents a promising therapeutic candidate for managing DIC, with Nrf2 as a key target.
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
01:26Heart Failure Drugs: Inotropic Agents