Ginsenoside Rg3 alleviates allergic rhinitis by regulating NLRP3-mediated inflammatory response and pyroptosis through SIRT6

Background

Allergic rhinitis (AR) is positively correlated with pyroptosis induced by NLR family pyrin domain containing 3 (NLRP3). Here, the effect of ginsenoside Rg3 on pyroptosis in the progression of AR was evaluated.

Methods

Human nasal epithelial cells (HNEPCs) were exposed to house dust mite (HDM) allergen to establish an AR cell model. Cell viability and pyroptosis were tested utilizing CCK-8 and flow cytometry. RT-qPCR and Western blot were used to detect mRNA and protein expression. Co-immunoprecipitation (Co-IP) assay was adopted to validate the molecular interaction. IgE, IL-4, IL-5, IL-13, IL-1β and IL-18 were detected by ELISA. AR mouse model was established using OVA and aluminum hydroxide. The sneezing frequency and nose rubbing frequency of mice were evaluated. HE staining was used to evaluate the pathological changes of nasal mucosa. Pyroptosis was detected by TUNEL and GSDMD staining.

Results

Ginsenoside Rg3 blocked NLRP3 inflammasome activation and pyroptosis induced by HDM allergen in HNEPCs, and increased cell activity inhibited by HDM. SIRT6 depletion overturned the suppressive effect of ginsenoside Rg3 on HDM-caused inflammation and pyroptosis in HNEPCs. Blocking SIRT6 diminished ginsenoside Rg3's protective role against sneezing and rubbing nose, inflammation and pyroptosis in AR mice. Furthermore, Co-IP assay confirmed that SIRT6 interacted with NLRP3 protein in HNEPCs. SIRT6 overexpression could decrease NLRP3 acetylation level and reduce NLRP3 expression.

Conclusion

Our results reveal that ginsenoside Rg3 mitigates AR by controlling NLRP3-triggered inflammatory response and pyroptosis via SIRT6, which provides a new therapeutic strategy for AR treatment.