Herniarin mitigates inflammation, oxidative stress, and apoptosis in experimental serous otitis media via NRF2/HO-1 and NLRP3/Caspase-1 pathways

Objective Serous otitis media (SOM) is a prevalent inflammatory condition of the middle ear. Herniarin (7-methoxycoumarin) is a coumarin derivative with anti-inflammatory and antioxidant properties. This study aimed to investigate the therapeutic potential of herniarin against experimentally induced SOM in rats, focusing on the NRF2/HO-1 and NLRP3/Caspase-1 pathways. Methods Thirty six adult male Wistar rats were allocated into six groups (n = 6): Control, Herniarin 200 mg/kg, Otitis, Otitis + Herniarin 100 mg/kg, Otitis + Herniarin 200 mg/kg, and Otitis + Dexamethasone. SOM was induced by established experimental protocols, and treatments were administered for seven consecutive days. Serum cytokines (IL-1β, TNF-α, IL-18), oxidative stress markers (GSH, SOD, MDA), histopathology, RT-qPCR, and Western blot analyses were performed. Results Serum levels of IL-1β, TNF-α, and IL-18 were significantly elevated in the otitis group compared with controls (p < 0.0001) and were markedly attenuated by herniarin and dexamethasone. Herniarin restored depleted GSH and SOD levels while reducing elevated MDA concentrations. Histopathological examination demonstrated dose-dependent attenuation of inflammatory cell infiltration, hemorrhage, and tympanic membrane damage. RT-qPCR showed that herniarin suppressed the upregulation of HO-1, NRF2, NF-κB, and Caspase-3 gene expression induced by otitis, while restoring Bcl-2 expression toward control levels. Western blot confirmed that herniarin reduced the expression of NLRP3, Caspase-1, and Caspase-3, and of NF-κB, while increasing Bcl-2 levels. Conclusion Herniarin exerts protective effects against experimental SOM by modulating the NRF2/HO-1 antioxidant defense system and suppressing NLRP3 inflammasome-mediated inflammation and apoptosis, suggesting its potential as a therapeutic candidate for otitis media.