Herbal Compound Improves Heart Health by Boosting Mitochondrial Stress Response

Jenn Hoskins
18th August, 2024

Herbal Compound Improves Heart Health by Boosting Mitochondrial Stress Response

Image Source: Natural Science News, 2024

Key Findings

  • Researchers at Guangzhou Hospital found that Salvianolic acid B (Sal B) protects the heart from septic injury
  • Sal B improved heart function, reduced inflammation, and lessened heart damage in mice with septic heart injury
  • Sal B activated a protective cellular mechanism called UPRmt, which helps repair and maintain mitochondrial function
Septic cardiomyopathy, a condition characterized by impaired heart function and mitochondrial activity dysregulation, poses significant challenges in emergency and critical care. Recent research from the Guangzhou Hospital of Integrated Traditional and Western Medicine has explored the protective effects of Salvianolic acid B (Sal B), a compound derived from the traditional Chinese medicine Salvia miltiorrhiza, on septic heart injury, with a particular focus on the mitochondrial unfolded protein response (UPRmt)[1]. Mitochondria are essential organelles responsible for energy production and regulation of cell death. However, they are susceptible to damage from reactive oxygen species and DNA mutations, which can disrupt protein folding and impair function. To counteract these stresses, cells have developed protective mechanisms, including the UPRmt, which promotes mitochondrial repair and aids in cell survival during stress[2]. This study aimed to investigate how Sal B influences UPRmt and its potential therapeutic effects on septic cardiomyopathy. In this study, researchers used an in vivo mouse model of lipopolysaccharide (LPS)-induced heart injury to evaluate Sal B's protective role. Additionally, cell models stimulated by LPS were developed to understand the mechanisms of Sal B on UPRmt. Techniques such as quantitative polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence were employed for molecular analysis. The results demonstrated that Sal B, administered at doses of 10, 30, and 60 mg/kg, significantly improved cardiac contractile function, reduced heart inflammation, and mitigated cardiac injury in LPS-exposed mice. In cardiomyocytes, LPS induced apoptosis (programmed cell death), increased mitochondrial reactive oxygen species (ROS) levels, promoted mitochondrial fission (division), and decreased mitochondrial membrane potential. Sal B alleviated all these detrimental effects. Mechanistically, Sal B was found to induce UPRmt both in vivo and in vitro. ATF5, a known UPRmt activator, was modulated by LPS and Sal B, resulting in increased ATF5 expression and its translocation from the cytosol to the nucleus. When ATF5-siRNA was used to inhibit ATF5 expression, it reversed the UPRmt upregulation, exacerbated mitochondrial dysfunction in LPS-stimulated cardiomyocytes, and counteracted the mitochondrial function enhancement seen in Sal B-treated cardiomyocytes. These findings align with earlier studies that have highlighted the importance of UPRmt in maintaining mitochondrial function under stress conditions. For example, research using the model organism Caenorhabditis elegans has shown that perturbation of the protein-folding environment in the mitochondrial matrix selectively upregulates the expression of nuclear genes encoding mitochondrial chaperones, which are crucial for coping with mitochondrial stress[3]. This underscores the role of UPRmt in promoting mitochondrial repair and cell survival, a mechanism that Sal B appears to enhance in the context of septic cardiomyopathy. In conclusion, this study provides compelling evidence that Sal B confers cardiac protection by enhancing UPRmt, highlighting its potential as a therapeutic approach for mitigating mitochondrial dysfunction in septic cardiomyopathy. These findings pave the way for further research into the clinical applications of Sal B and the development of targeted therapies to improve outcomes in patients suffering from septic cardiomyopathy.

MedicineHealthBiochem

References

Main Study

1) Salvianolic acid B improves mitochondrial dysfunction of septic cardiomyopathy via enhancing ATF5-mediated mitochondrial unfolded protein response.

Published 15th August, 2024

https://doi.org/10.1016/j.taap.2024.117072

Related Studies

2) Mitochondrial recovery by the UPRmt: Insights from C. elegans.

https://doi.org/10.1016/j.semcdb.2023.02.002

3) Ubiquitin-like protein 5 positively regulates chaperone gene expression in the mitochondrial unfolded protein response.

Journal: Genetics, Issue: Vol 174, Issue 1, Sep 2006


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