Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2023.194
Elafibranor PPARα/δ Dual Agonist Ameliorates Ovalbumin-Induced Allergic Asthma
Ye-Eul Lee and Dong-Soon Im*
Department of Fundamental Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02446, Republic of Korea
*E-mail: imds@khu.ac.kr
Tel: +82-2-961-9377, Fax: +82-2-961-9580
Received: November 5, 2023; Revised: December 16, 2023; Accepted: December 20, 2023; Published online: June 5, 2024.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Asthma is characterized by chronic inflammation and respiratory tract remodeling. Peroxisome proliferator-activated receptors (PPARs) play important roles in the pathogenesis and regulation of chronic inflammatory processes in asthma. The role of PPARγ has been studied using synthetic PPARγ agonists in patients with asthma. However, involvement of PPARα/δ has not been studied in asthma. In the present study, we investigated if elafibranor, a PPARα/δ dual agonist, can modulate ovalbumin (OVA)-induced allergic asthma, which is a potential drug candidate for non-alcoholic fatty liver in obese patients. Elafibranor suppresses antigeninduced degranulation in RBL-2H3 mast cells without inducing cytotoxicity in vitro. In mice with OVA-induced allergic asthma, the administration of elafibranor suppressed OVA-induced airway hyper-responsiveness at a dose of 10 mg/kg. Elafibranor also suppressed the OVA-induced increase in immune cells and pro-inflammatory cytokine production in the bronchoalveolar lavage fluid (BALF). Histological studies suggested that elafibranor suppressed OVA-induced lung inflammation and mucin hyper-production in the bronchial airways. In addition, elafibranor suppressed OVA-induced increases in serum immunoglobulin E and IL-13 levels in BALF. Conversely, the present study suggests that elafibranor has the potential for use in patients with allergic asthma.
Keywords: Asthma, Allergy, Elafibranor, Immunopharmacology, PPAR


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