Luteolin alleviates olfactory dysfunction in eosinophilic chronic rhinosinusitis through modulation of the TLR4/NF-κB...

Eosinophilic chronic rhinosinusitis (ECRS) is characterized by early, severe olfactory dysfunction and a high recurrence rate, with inadequate treatments. This article aims to elucidate the potential mechanisms by which luteolin may treat olfactory dysfunction in the context of ECRS.

Thirty C57 BL/6 mice were randomly assigned to five groups: a control group and four experimental groups (ECRS, ECRS + Luteolin (Low, Medium, High Dose)). We conducted RNA sequencing, behavioral testing, ELISA, PCR, HE staining, Western blot analysis, and immunofluorescence staining. Additionally, human olfactory epithelial Cells (HOEPCs) were treated with Luteolin, TAK-242, QNZ, and Luteolin + LPS to investigate the underlying mechanisms.

Luteolin significantly reduced IL-4, IL-5, and IL-13 levels in the nasal lavage fluid (NLF) of ECRS mice, improving olfactory function and restoring OMP⁺ mature and Gap43⁺ immature olfactory sensory neurons (OSNs). RNA sequencing revealed the involvement of the TLR4/NF-κB pathway in ECRS-related olfactory dysfunction and luteolin's therapeutic effects. Luteolin reduced TLR4⁺ cells, P65 nuclear translocation, and decreased protein levels of IL-1β, TLR4, MyD88, p-P65, P65, and p-P38. The treatment also lowered OSNs cell apoptosis by decreasing the levels of cleaved caspase-3 and caspase-9 levels, and increasing Bcl-2 protein. Antioxidant enzymes SOD, CAT, and GSH-Px were elevated, while MDA levels decreased. In ECRS HOEPCs, luteolin's anti-apoptotic effects on OSNs were reversed by LPS-induced TLR4/NF-κB activation.

Luteolin ameliorates olfactory dysfunction associated with ECRS by modulating the TLR4/NF-κB signaling pathway. This modulation results in a reduction of T_H2-type inflammation, oxidative stress, and apoptosis in OSNs.