Nrf2 mediated signaling axis in sepsis-induced cardiomyopathy: potential Pharmacological receptor

Sepsis has emerged as the most pressing health concerns globally in emergency and intensive care unit. Sepsis-Induced Cardiomyopathy (SIC) represents an acute cardiac insufficiency syndrome secondary to sepsis, characterized by a high incidence and a significant increase in mortality among sepsis patients. To date, no specific treatment exists for this condition. In recent years, mounting evidence has indicated that Nrf2 plays a critical protective role in SIC and may represent a potential therapeutic target.

Pubmed database literature was searched for studies pertaining to the role of Nrf2 in sepsis, from the inception of the database to October 1, 2024. Biorender software was performed to draw the corresponding mechanism diagram.

Using the keywords "Nrf2 and Sepsis", we initially identified 454 articles. To refine our search, we employed "Nrf2 and Sepsis and Cardiac" as keywords, yielding 63 articles. Upon reviewing the full texts, we selected 26 studies for inclusion in our review. Nrf2 is implicated in various protective aspects against cardiomyocyte injury stemming from sepsis, including its inhibitory effects on inflammation, apoptosis, mitochondrial dysfunction, pyroptosis, and ferroptosis. 23 natural compounds under investigation for this application were identified.

The Nrf2-mediated signaling pathway plays a critical role in sepsis-induced myocardial injury. Given the complex, systemic, and multifactorial nature of sepsis, these natural compounds should be regarded as adjunctive therapeutic options for scholarly investigation rather than standalone therapeutic interventions. Substantial future research will still be required to validate their clinical efficacy and mechanistic roles.