2. Academic Validation
  3. Dihydrocapsaicin attenuates oxidative stress and apoptosis in acute myocardial infarction via promoting Raf-1/ASK1 complex formation

Dihydrocapsaicin attenuates oxidative stress and apoptosis in acute myocardial infarction via promoting Raf-1/ASK1 complex formation

  • Phytomedicine. 2025 Oct:146:157126. doi: 10.1016/j.phymed.2025.157126.
Yanmin Chen 1,  Jiaying Yu 2,  Hualing He 1,  Wencai Xu 1,  Binghua Yi 1,  Xingyu Lin 1,  Qiulu Yu 1,  Zhonghao Lin 1,  Jiafeng Lin 1,  Cong Lin 3,  Chenchen Cai 4,  Kaiyu Huang 5
Affiliations

Affiliations

  • 1 Department of Cardiology, Key Laboratory of Panvascular Diseases of Wenzhou, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
  • 2 Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.
  • 3 Department of Cardiology, Key Laboratory of Panvascular Diseases of Wenzhou, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China. Electronic address: lincong0577@aliyun.com.
  • 4 Department of Physical Medicine and Rehabilitation, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China. Electronic address: 219096@wzhealth.com.
  • 5 Department of Cardiology, Key Laboratory of Panvascular Diseases of Wenzhou, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China. Electronic address: hky@wmu.edu.cn.
PMID: 40768809 DOI: 10.1016/j.phymed.2025.157126
Abstract

Background: Acute myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. Dihydrocapsaicin (DHC), a natural antioxidant derived from Plants, has demonstrated pharmacological effects in various diseases. However, its research in the cardiovascular field remains relatively limited.

Purpose: This study aimed to explore the anti-oxidative and anti-apoptotic effects of DHC on MI and its underlying mechanisms.

Methods: The MI model was established by left coronary artery ligation. In vitro, the H9c2 cardiomyocyte injury model was established via oxygen-glucose deprivation (OGD). Myocardial injury was assessed by echocardiography, infarct size, histopathological changes, and serological testing. TUNEL assay, Annexin V/PI staining assay, DHE, DCFH-DA staining and western blot analysis were used to validate cell Apoptosis and oxidative stress level. The target of DHC was investigated using immunofluorescence, biotin pull-down assays, molecular docking, molecular dynamics simulations, cellular thermal shift assays (CETSA), and drug affinity responsive target stability (DARTS). Subsequently, the molecular mechanism of the interaction between Raf-1/ASK1 complex and DHC was investigated. Moreover, Raf-1 silencing or ASK1 overexpression H9c2 cardiomyocytes were used for further validation.

Results: DHC was found to exert anti-oxidative and anti-apoptotic effects, attenuating cardiac dysfunction and injury in the MI model and protecting against OGD-induced injury in H9c2 cardiomyocytes. Mechanistically, Raf-1 was identified as a direct target of DHC. The protection of DHC against superoxide production and apoptotic cell death was compromised with Raf-1 silencing. Additionally, we found that DHC enhance the interaction between Raf-1 and ASK1, inhibiting the activation of the p-ASK1/p-JNK/p-P38 signaling pathway during OGD insult. The overexpression of ASK1 abolished the above protective effects of DHC.

Conclusion: Our results demonstrated that DHC may serve as a promising therapeutic agent for attenuating cardiac dysfunction after MI by alleviating oxidative stress and Apoptosis.

Keywords

Acute Myocardial Infarction; Apoptosis; Dihydrocapsaicin; Oxidative Stress; Raf-1/ASK1 Complex.

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