Pluviatolide Attenuates Type I Hypersensitivity through Regulation of Mast Cell Activation
10.4062/biomolther.2025.164
- Author:
Seon Young KIM
1
;
Jeong Won PARK
;
Juhyun SHIN
;
Ji-Ae LEE
;
Sun-Hee LEEM
;
Min Geun JO
;
Min Yeong CHOI
;
Wahn Soo CHOI
;
Keun Young MIN
;
Geunwoong NOH
;
Sung-Jin BAE
;
Yung Hyun CHOI
;
Hyuk Soon KIM
Author Information
1. Department of Biomedical Sciences, College of Natural Science and Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2026;34(2):413-422
- CountryRepublic of Korea
- Language:English
-
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 marrowderived 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 receptorindependent, 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.
