Vernodalin Alleviates Cardiotoxicity and Inflammation in Isoproterenol-Mediated Myocardial Infarction through NF-κB/AMPK Signaling Pathways in Rats

  • Comb Chem High Throughput Screen. 2025;28(9):1594-1603. doi: 10.2174/0113862073302291240528055742.
Tao Tao  1 ,  Xiaona Sun  2 ,  Tuowei Zhang  1 ,  Annamalai Vijayalakshmi  3 ,  Fangqiao Niu  4
Affiliations
  • 1. Department of Cardiovascular Medicine, Xi'an Hospital of Traditional Chinese Medicine Xi'an, 710016, China.
  • 2. Department of Cardiology, Laizhou City People's Hospital, Yantai, 261400, China.
  • 3. Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar, Chidambaram, Tamilnadu, India.
  • 4. Department of Medical Rehabilitation, The Third Affiliated Hospital of Air Force Medical University, Xi'an, 710032, China.
PMID: 38840392 DOI: 10.2174/0113862073302291240528055742
Abstract

Background: Myocardial infarction (MI) is the foremost cause of mortality in cardiovascular diseases. MI ultimately exacerbates cardiotoxicity due to the release of toxicity biomarkers and inflammatory infiltration.

Aim: Vernodalin (VN) is a renowned cytotoxic sesquiterpene lactone that possesses antioxidant, Anticancer, and anti-inflammatory properties. The cardioprotective mechanism of VN remains concealed. Hence, we explored the cardioprotective efficacy of VN on isoproterenol (ISO)- mediated MI and analyzed its underlying mechanism.

Methods: To investigate the cardioprotective potential of VN (10 mg/kg bw), Wistar albino rats were subcutaneously injected with ISO (85 mg/kg bw) to induce MI. The assessment included measurements of heart weight/body weight index, hemodynamics, toxicity Enzymes, histology, inflammatory mediators, and signaling pathway. While decreasing hemodynamic parameters and VEGF-B, AMPK, and eNOS signaling pathways, ISO increased heart weight/body weight index, cardiotoxicity Enzymes, biomarkers, inflammation, and histological alterations.

Results: Treatment with VN could significantly (pπ0.05) mitigate the heart weight/body weight index, cardiotoxicity Enzymes, biomarkers, inflammatory cytokines, and histopathological changes while enhancing hemodynamic parameters and VEGF-B, AMPK, and eNOS signaling pathways. Collectively, our findings revealed that the VN ameliorated defensive action against MI and averted myocardial injury by reducing the NF-κB-mediated inflammatory pathways in rats.

Conclusion: These findings established that VN expressively preserves the myocardium and employs anti-inflammatory actions by regulating NF-κB, VEGF-B, AMPK, and eNOS signaling pathways.

Keywords
VEGF-B/AMPK/eNOS signaling; Vernodalin; cardiovascular diseases (CVD).; inflammation; isoproterenol; myocardial infarction.
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