2. Academic Validation
  3. Free fatty acid 3 receptor agonist AR420626 reduces allergic responses in asthma and eczema in mice

Free fatty acid 3 receptor agonist AR420626 reduces allergic responses in asthma and eczema in mice

  • Int Immunopharmacol. 2024 Jan 25:127:111428. doi: 10.1016/j.intimp.2023.111428.
Ye-Ji Lee 1,  So-Eun Son 2,  Dong-Soon Im 3
Affiliations

Affiliations

  • 1 Department of Biomedical and Pharmaceutical Sciences, Seoul 02446, Republic of Korea.
  • 2 Department of Fundamental Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02446, Republic of Korea.
  • 3 Department of Biomedical and Pharmaceutical Sciences, Seoul 02446, Republic of Korea; Department of Fundamental Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02446, Republic of Korea. Electronic address: imds@khu.ac.kr.
PMID: 38159551 DOI: 10.1016/j.intimp.2023.111428
Abstract

Free fatty acid 3 receptor (FFA3; previously GPR41) is a G protein-coupled receptor that senses short-chain fatty acids and dietary metabolites produced by the gut microbiota. FFA3 deficiency reportedly exacerbates inflammatory events in asthma. Herein, we aimed to determine the therapeutic potential of FFA3 agonists in treating inflammatory diseases. We investigated the effects of N-(2,5-dichlorophenyl)-4-(furan-2-yl)-2-methyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxamide (AR420626), an FFA3 agonist, in in vivo models of chemically induced allergic asthma and eczema in BALB/c mice. Administration of AR420626 decreased the number of immune cells in the bronchoalveolar lavage fluid and skin. AR420626 suppressed inflammatory cytokine expression in the lung and skin tissues. Histological examination revealed that AR420626 suppressed inflammation in the lungs and skin. Treatment with AR420626 significantly suppressed the enhanced lymph node size and inflammatory cytokine levels. Overall, FFA3 agonist AR420626 could suppress allergic asthma and eczema, implying that activation of FFA3 might be a therapeutic target for allergic diseases.

Keywords

Anti-allergic; Anti-asthmatic; Anti-eczema; FFA3; Free fatty acid receptor 3; Short-chain fatty acids.

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