Tongxinbi formula improved cardiac function and reduced myocardial fibrosis by activating the Keap1/Nrf2 pathway, mitigating oxidative stress and inflammation post-MI.
Does Tongxinbi formula attenuate post-MI cardiac injury and remodeling in a murine model?
Tongxinbi formula exerts anti-fibrotic and cardioprotective effects in a post-MI murine model by activating Nrf2 signaling to mitigate oxidative stress and inflammation.
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Background: Myocardial infarction (MI) remains a major global public health challenge. Although advances in reperfusion therapy have reduced acute mortality, post-infarction cardiac remodeling continues to pose a substantial threat to long-term cardiovascular health. Oxidative stress and the ensuing inflammatory response are key drivers of this pathological process, leading to cardiomyocyte death, myocardial fibrosis, and functional impairment. Among the regulatory pathways involved, the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis has emerged as a critical therapeutic target for mitigating post-MI cardiac injury. Methods: A murine MI model was established by permanent ligation of the left anterior descending coronary artery. Mice received oral Tongxinbi formula (TXB) at low, medium, or high doses (9/18/36 g/kg) once daily for 28 days. Cardiac function was assessed by echocardiography; myocardial fibrosis by Masson’s trichrome; and endothelial integrity by CD31 immunofluorescence. Plasma markers of endothelial function and inflammation were quantified. In vitro, oxidative stress was induced by H 2 O 2 in vascular endothelial cells and cardiomyocytes, followed by treatment with TXB drug-containing serum. Western blot and RT-qPCR were used to measure components of the Keap1/Nrf2 pathway; ELISA quantified oxidative stress and inflammatory indices. Conditioned-medium experiments evaluated endothelial cell–mediated paracrine protection of cardiomyocytes. Results: TXB significantly improved cardiac function and reduced myocardial fibrosis after MI, in association with preservation of microvascular structure and systemic attenuation of oxidative stress and inflammation. In vitro, TXB activated the endothelial Keap1/Nrf2 pathway, enhanced cellular antioxidant defenses, increased VEGF secretion, and, via endothelial cell-mediated paracrine signaling, alleviated cardiomyocyte injury under oxidative stress. Conclusion: TXB exerts anti-fibrotic and cardioprotective effects by activating Nrf2 signaling and engaging endothelial-mediated paracrine mechanisms, collectively mitigating oxidative stress and inflammation in the post-MI setting.
Zhu et al. (Thu,) reported a other. Tongxinbi formula improved cardiac function and reduced myocardial fibrosis by activating the Keap1/Nrf2 pathway, mitigating oxidative stress and inflammation post-MI.