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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1401273

Kaempferol activates chloride secretion via the cAMP/PKA signaling pathway and expression of CFTR in T84 cells

Provisionally accepted
Janjira Thaweewattanodom Janjira Thaweewattanodom 1Chatsri Deachapunya Chatsri Deachapunya 1Sutthasinee Poonyachoti Sutthasinee Poonyachoti 2*
  • 1 Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand
  • 2 CU-Animal Fertility Research Unit, Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, Bangkok, Thailand

The final, formatted version of the article will be published soon.

    Kaempferol is a flavonol identified as the most potent activator of chloride (Cl -) secretion among other flavonoids in airway epithelial cells. This study aimed to investigate the cellular mechanisms by which kaempferol stimulates Cl -secretion in the T84 human colon carcinoma cell line by Ussing chambers and voltage clamp technique. Bilateral addition of kaempferol (1-100 µM) increased shortcircuit current (Isc) in a concentration-dependent manner. Ion substitution of Cl -or CFTR inhibitors NPPB and glibenclamide or a Na + /K + /2Cl -cotransporter inhibitor bumetanide attenuated kaempferolinduced Isc response. In permeabilized monolayers, selective channel inhibitors CFTRinh-172 and CaCCinh-A01 inhibited kaempferol-induced apical Cl -current (ICl), and K + blockers BaCl2 and clotrimazole inhibited basolateral K + current (IKb). The kaempferol-induced ICl showed no additive effects with forskolin or 8cpt-cAMP. The kaempferol-induced ICl was mostly abolished by protein kinase A inhibitor H89, but not by tyrosine kinase inhibitors, AG490 and tyrphostin A23, or tyrosine phosphatase inhibitor vanadate. Treatment with kaempferol for 24 h increased the expression of CFTR protein as determined by the Western blot analysis. These results demonstrated that kaempferol activates Cl -secretion across T84 cells by activating the apical Cl -current and basolateral K + current. The mechanisms may involve the cAMP/PKA pathway and CFTR expression. Taken together, these findings reveal the beneficial effects of kaempferol to increase fluid secretion which can be used to treat constipation.

    Keywords: Kaempferol, T84 cells, Cl -secretion, short-circuit current, Apical Cl -current

    Received: 15 Mar 2024; Accepted: 29 Aug 2024.

    Copyright: © 2024 Thaweewattanodom, Deachapunya and Poonyachoti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Sutthasinee Poonyachoti, CU-Animal Fertility Research Unit, Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, 10330, Bangkok, Thailand

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.