Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Elafibranor PPARα/δ Dual Agonist Ameliorates Ovalbumin-Induced Allergic Asthma

  • Ye-Eul Lee (Department of Fundamental Pharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Dong-Soon Im (Department of Fundamental Pharmaceutical Sciences, Graduate School, Kyung Hee University)
  • Received : 2023.11.05
  • Accepted : 2023.12.20
  • Published : 2024.07.01
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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 antigen-induced 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

Acknowledgement

This research was supported by the Basic Science Research Program of the Korean National Research Foundation funded by the Korean Ministry of Science, ICT, and Future Planning (NRF-2023R1A2C2002380).

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