Herniarin mitigates inflammation, oxidative stress, and apoptosis in experimental serous otitis media via NRF2/HO-1 and NLRP3/Caspase-1 pathways
Auris Nasus Larynx, vol.53, no.4, pp.514-523, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 53 Issue: 4
- Publication Date: 2026
- Doi Number: 10.1016/j.anl.2026.05.012
- Journal Name: Auris Nasus Larynx
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE
- Page Numbers: pp.514-523
- Keywords: Coumarin, Herniarin, Inflammation, NLRP3 inflammasome, NRF2/HO-1, Otitis media, Oxidative stress
- Erzincan Binali Yildirim University Affiliated: Yes
Abstract
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.