Rhftnorrhea ftn allergftc rhftnfttis (AR) fts characterftzed by the secretion of electrolytes ftn the nasal dftscharge. The secretion of Cl? and HCO3? fts maftnly regulated by cystic fibrosfts transmembrane conductance regulator (CFTR) or vfta the calcftumactivated Cl? channel anoctamftn-1 (ANO1) ftn nasal gland serous cells. Interleukftn-4 (IL-4), whftch fts crucftal ftn the development of allergftc ftnflammation, ftncreases the expressfton and activftty of ANO1 by stimulating hftstamftne receptors. In thfts study, we ftnvestigated ANO1 as a potential therapeutic target for rhftnorrhea ftn AR usftng an ANO1 ftnhftbfttor derftved from a natural herb. Ethanolftc extracts (30%) of Spirodela polyrhiza (SPEtOH) and ftts five major flavonoftds constituents were prepared. To elucftdate whether the activftty of human ANO1 (hANO1) was modulated by SPEtOH and ftts chemftcal constituents, a patch clamp experftment was performed ftn hANO1-HEK293T cells. Luteolftn, one of the major chemftcal constituents ftn SPEtOH, sftgnftficantly ftnhftbftted hANO1 activftty ftn hANO1-HEK293T cells. Further, SPEtOH and luteolftn specftfically ftnhftbftted the calcftum-activated chlorftde current, but not CFTR current ftn human aftrway epftthelftal Calu-3 cells. Calu-3 cells were cultured to confluency on transwell ftnserts ftn the presence of IL-4 to measure the electrolyte transport by Ussftng chamber. Luteolftn also sftgnftficantly ftnhftbftted the ATP-ftnduced ftncrease ftn electrolyte transport, whftch was ftncreased ftn IL-4 sensfttized Calu-3 cells. Our findftngs ftndftcate that SPEtOH- and luteolftn may be sufttable candftdates for the prevention and treatment of allergftc rhftnfttis. SPEtOH- and luteolftn-medftated ANO1 regulation provftdes a basfts for the development of novel approaches for the treatment of allergftc rhftnfttis-ftnduced rhftnorrhea.
Bibliographical noteFunding Information:
This research was supported by the Convergence of Conven onal Medicine and Tradi onal Korean Medicine ? 頀D program funded by the Ministry of Health 頀 Welarfe 縀Korea 缀 through the Korean Health Industry Development Ins tute 縀KHIDI 缀 g? rant number HI C 缀 and also supported by the Basic Science ?esearch Program through the Na onal ?esearch Founda on of Korea 縀N?F 缀 funded by the Ministry of Educa on 縀N?F 爃娃A A A 缃?
Thfts research was supported by the Convergence of Conventional Medftcftne and Tradfttional Korean Medftcftne R&D program funded by the Mftnftstry of Health & Welfare (Korea) through the Korean Health Industry Development Institute (KHIDI) (grant number HI16C0766) and also supported by the Basftc Scftence Research Program through the National Research Foundation of Korea (NRF) funded by the Mftnftstry of Education (NRF-2018R1A6A1A03023718).
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