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Published on: May 26, 2023
Dan Hong Injection Protects Against Cardiomyocytes Apoptosis by Maintaining Mitochondrial Integrity Through
Ling Zhang1, Yu Wang1, Chang Li1
1College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.
Insights
Danhong injection protects heart cells from injury by preserving mitochondrial function and reducing cell death. This study reveals its mechanism involves the Keap1/Nrf2/JNK pathway, offering a new treatment for myocardial ischemia/reperfusion injury.
Area of Science:
- Cardiology
- Mitochondrial Biology
- Pharmacology
Background:
- Danhong injection (DHI) is a traditional Chinese medicine used for cardiovascular diseases.
- Its mitochondria-protective effects in myocardial ischemia/reperfusion (I/R) injury are recognized but not fully understood.
- Understanding DHI's mechanism is crucial for optimizing its therapeutic application.
Purpose of the Study:
- To investigate the effect and mechanism of DHI on mitochondrial integrity and cardiomyocyte apoptosis following I/R injury.
- To elucidate DHI's role in protecting against hypoxia-reoxygenation (H/R) induced cellular damage.
- To identify the specific molecular pathways involved in DHI's cardioprotective actions.
Main Methods:
- Established an I/R rat model to assess infarct size, apoptosis, and oxidative stress.
- Utilized H9C2 cells subjected to H/R, with and without nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown.
- Evaluated apoptosis rates, reactive oxygen species (ROS) generation, ATP levels, mitochondrial membrane potential, and oxygen consumption.
- Analyzed the involvement of the Keap1/Nrf2/JNK pathway.
Main Results:
- DHI significantly reduced infarct size, apoptosis, and oxidative stress in I/R rat hearts.
- In vitro, DHI inhibited H/R-induced apoptosis, decreased ROS generation, and preserved mitochondrial integrity.
- DHI maintained mitochondrial morphology, alleviated dysfunction, increased ATP levels, and enhanced oxygen consumption.
- The Keap1/Nrf2/JNK pathway was identified as a key mediator of DHI's protective effects.
Conclusions:
- Danhong injection demonstrates significant cardioprotective effects against I/R injury by preserving mitochondrial integrity and inhibiting apoptosis.
- DHI exerts its protective effects via the Keap1/Nrf2/JNK pathway, modulating oxidative stress and mitochondrial function.
- These findings reveal a novel mechanism for DHI and position it as a promising mitochondrial protectant for myocardial I/R injury.
Abstract:
Danhong injection (DHI) is used widely against cardiovascular disease in China. Recent studies have demonstrated its mitochondria-protection effect as being pivotal in treatment of myocardial ischemia/reperfusion (I/R) injury, but the underlying mechanism of action is incompletely understood. We aimed to identify the effect and mechanism of action of DHI on mitochondrial integrity and cardiomyocyte apoptosis after I/R. An I/R rat model was induced to detect the effect of DHI on myocardial repair by infarct size, apoptosis and oxidative stress. In vitro, H9C2 cells or H9C2 cells with nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown were injured under hypoxia-reoxygenation (H/R). The effects of DHI on apoptosis, antioxidant capacity and mitochondrial integrity were evaluated by mitochondrial morphology, apoptosis rate, reactive oxygen species (ROS) generation, ATP levels, mitochondrial membrane potential, and oxygen consumption in H9C2 cells treated with H/R. The underlying mechanism of action of DHI in maintenance of mitochondrial integrity and anti-apoptosis was detected in H9C2 cells with or without Nrf2 knockdown. DHI treatment significantly decreased the infarct size, inhibited apoptosis and suppressed oxidative stress in the hearts of I/R rats. Also, DHI promoted cell survival by: an anti-apoptosis action; inhibiting ROS generation; maintaining mitochondrial morphology with increased mitochondrial length; alleviating mitochondrial dysfunction with a decreased mitochondrial membrane potential; increasing ATP levels and the oxygen-consumption rate. Moreover, the Keap1/Nrf2/JNK pathway was found to be involved in DHI reducing oxidative stress and maintaining mitochondrial integrity. We revealed a novel mechanism by which DHI protected H9C2 cells against H/R injury via the Keap1/Nrf2/JNK pathway and provided a mitochondrial protectant for the treatment of myocardial I/R injury.
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