Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Pluviatolide Attenuates Type I Hypersensitivity through Regulation of Mast Cell Activation

  • Seon Young Kim (Department of Biomedical Sciences, College of Natural Science and Department of Health Sciences, The Graduate School of Dong-A University) ;
  • Jeong Won Park (Department of Biomedical Sciences, College of Natural Science and Department of Health Sciences, The Graduate School of Dong-A University) ;
  • Juhyun Shin (Department of Biomedical Sciences, College of Natural Science and Department of Health Sciences, The Graduate School of Dong-A University) ;
  • Ji-Ae Lee (Department of Biomedical Sciences, College of Natural Science and Department of Health Sciences, The Graduate School of Dong-A University) ;
  • Sun-Hee Leem (Department of Biomedical Sciences, College of Natural Science and Department of Health Sciences, The Graduate School of Dong-A University) ;
  • Min Geun Jo (Department of Immunology, College of Medicine, Konkuk University) ;
  • Min Yeong Choi (Department of Immunology, College of Medicine, Konkuk University) ;
  • Wahn Soo Choi (Department of Immunology, College of Medicine, Konkuk University) ;
  • Keun Young Min (Department of Microbiology and Immunology, Weill Cornell Medicine) ;
  • Geunwoong Noh (Department of Allergy, Allergy and Clinical Immunology Center, Cheju Halla General Hospital) ;
  • Sung-Jin Bae (Department of Molecular Biology and Immunology, Kosin University College of Medicine) ;
  • Yung Hyun Choi (Basic Research Laboratory for the Regulation of Microplastic-Mediated Diseases, Department of Biochemistry, College of Korean Medicine, Dong-eui University) ;
  • Hyuk Soon Kim (Department of Biomedical Sciences, College of Natural Science and Department of Health Sciences, The Graduate School of Dong-A University)
  • Received : 2025.08.26
  • Accepted : 2026.01.16
  • Published : 2026.03.01
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Abstract

This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptor-independent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.

Keywords

Acknowledgement

This research was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (NRF-2020R1C1C1003676), and the National Research Foundation of Korea’s Brain Korea 21 FOUR Program.

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