Narciclasine mitigates sepsis-induced cardiac dysfunction by enhancing BNIP3-mediated mitophagy and suppressing ferroptosis

Prophylactic administration of Narciclasine (Narc) improved 72-hour survival and restored cardiac function in sepsis models.

• Narc demonstrated antioxidant and anti-inflammatory properties in mouse models of sepsis-induced myocardial dysfunction.
• Cardiac function metrics, such as left ventricular ejection fraction and cardiac output, were significantly improved in a dose-dependent manner following Narc treatment.
• Biochemical assays indicated that sepsis-induced hearts exhibited signs of ferroptosis, including iron overload and lipid peroxidation, which were mitigated by Narc.
• Narc treatment led to increased levels of glutathione and upregulation of protective proteins involved in cellular stress response.
• Cell viability in neonatal rat cardiomyocytes was preserved by Narc in the presence of inflammatory and ferroptosis-inducing stimuli.
• Network pharmacology identified BNIP3 as a key target, and its silencing diminished the protective effects of Narc in both cellular and animal models.

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