In-silico and In-vivo Investigations Reveal Ameliorative Potential of Myricetin Against Doxorubicin-induced Myocardial Damage via Modulation of NF-κB Signaling Pathway

Introduction: Although Doxorubicin (DOX) is an effective anticancer agent, its cardiotoxicity limits clinical use. DOX-induced oxidative stress augments NF-κB expression, elevates inflammatory cytokines, and causes myocardial injury. Since the flavonoid Myricetin (MYR) has antioxidant, anti-inflammatory, and NF-κB-inhibitory properties, we investigated its potential to mitigate DOX-induced cardiotoxicity in rats. Method: Molecular docking of MYR was performed against NF-κB and proinflammatory cytokines (TNF-α, IL-1β, IL-6). After confirming binding affinities, DOX was administered to rats on days 1, 3, 5, 7, and 9, while MYR was given daily for 9 days. On day 10, hemodynamic parameters were recorded, and blood and heart tissues were collected. Serum transaminases (SGPT, SGOT) and cardiac markers (CK-MB, LDH) were measured. Oxidative stress markers (CAT, SOD, GSH, MDA), proinflammatory cytokines (TNF-α, IL-1β, IL-6), NO, NF-κB levels, and myocardial histopathology were assessed. Results: MYR exhibited strong binding affinity to target proteins. In vivo, MYR significantly attenuated DOX-induced ECG (ST height) alterations and reduced serum SGPT, SGOT, CK-MB, and LDH levels. In cardiac tissue, MYR enhanced CAT, SOD, and GSH, while reducing MDA. MYR also decreased NF-κB, NO, TNF-α, IL-1β, and IL-6 levels, and improved histopathological features. Discussion: These findings suggest that MYR effectively counteracts DOX-induced myocardial injury by suppressing NF-κB-mediated inflammatory pathways and oxidative stress, supporting its therapeutic potential in cardioprotection. Conclusion: MYR mitigates DOX-induced cardiotoxicity through antioxidant and antiinflammatory mechanisms involving inhibition of NF-κB signaling.