Hyperforin modulates MAPK/CCL11 signaling to reduce the inflammatory response of nasal mucosal epithelial cells caused by allergic rhinitis by targeting BCL6.

Abstract

Hyperforin is a type of bicyclic tetraketone with four isoprenoid chains extracted from Hypericum perforatum L. that has multiple biological activities such as anti-diabetes, antitumor and anti-inflammation. However, the role and potential mechanism of hyperforin in allergic rhinitis (AR) remains to be clarified. In the present study, cell viability was analyzed using Cell Counting Kit-8 assay, while inflammation was detected using ELISA and reverse transcription-quantitative PCR. Epithelial cell barrier damage was measured using western blotting and immunofluorescence staining. The expression levels of B-cell lymphoma 6 (BCL6) and the p38 MAPK/C-C motif chemokine 11 (CCL11) pathway were detected using western blotting. In addition, the association between hyperforin and BCL6 was analyzed by SWISS TargetPrediction, DisGeNET, Gene Ontology and Pathway databases. Molecular docking was performed using AutoDockTools 1.5.6 and Discovery Studio 4.5 software. The data demonstrated that there were 16 interlinking target genes of hyperforin with AR, in which BCL6 was the most relevant one with hyperforin in AR. The binding between hyperforin and BCL6 was verified, and molecular docking was modeled. The results revealed that hyperforin inhibited IL-13-induced nasal epithelial inflammatory cytokine release and repressed the damage to the cellular barrier from IL-13 stimulation. In addition, hyperforin activated BCL6 expression and significantly suppressed the expression of p38 MAPK/CCL11. Silencing of BCL6 reversed the effects of hyperforin on IL-13-induced inflammation and barrier damage. In summary, the present results revealed that hyperforin suppressed IL-13-induced nasal epithelial cell inflammation and barrier damage by targeting BCL6/p38 MAPK/CCL11, which may provide promising therapeutic targets for AR.

• Authors: Chen Xu, Wen Su
• Journal: Experimental and therapeutic medicine (Exp Ther Med) Vol. 26 Issue 6 Pg. 579 (Dec 2023) ISSN: 1792-1015 [Electronic] Greece
• PMID: 38023351 (Publication Type: Journal Article)
• Copyright: Copyright: © Xu et al.