Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Curcumenol Inhibits Mast Cells Activation in Ovalbumin-Induced Anaphylaxis Model Mice through Modulation of the Fc Epsilon Receptor I Signaling Pathway

  • Yun-Mi Kang (KM Application Center, Korea Institute of Oriental Medicine) ;
  • Ki-Shuk Shim (KM Convergence Research Division, Korea Institute of Oriental Medicine) ;
  • Sung-Wook Chae (KM Convergence Research Division, Korea Institute of Oriental Medicine) ;
  • So-Hyeon Bok (College of Oriental Medicine, Dongshin University) ;
  • Dae-Hun Park (College of Oriental Medicine, Dongshin University) ;
  • Kyungho Kim (KM Application Center, Korea Institute of Oriental Medicine) ;
  • Bonggi Lee (Department of Food Science and Nutrition, Pukyong National University) ;
  • Su-Yeon Park (Department of Smart Green Technology Engineering, Pukyong National University) ;
  • Taesoo Kim (KM Convergence Research Division, Korea Institute of Oriental Medicine) ;
  • Ki Mo Kim (KM Convergence Research Division, Korea Institute of Oriental Medicine)
  • Received : 2025.03.10
  • Accepted : 2025.05.26
  • Published : 2025.07.01
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Abstract

Curcumenol, a sesquiterpene isolated from Curcuma zedoaria, has a variety of therapeutic effects, such as neuroprotective, antitumor and hepatoprotective effects. This study elucidates whether curcumenol can inhibit ovalbumin (OVA)-induced allergic reactions in a mouse and monoclonal anti-2,4,6-dinitrophenyl (DNP)-immunoglobulin (IgE)/bovine serum albumin (BSA)-mediated allergic reactions in mouse bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia cells (RBL-2H3). IgE-mediated passive cutaneous anaphylaxis and ovalbumin (OVA)-induced anaphylaxis mouse models were performed. β-hexosaminidase release and mast cell degranulation were analyzed in vitro. Western blot analyses were performed to validate the effect of curcumenol on FcεRI signaling pathway. Molecular docking analysis were performed to evaluate curcumenol and tyrosine kinase interaction. Curcumenol alleviated OVA-induced anaphylactic allergic symptoms by increasing rectal temperature in a dosedependent manner. In addition, it reduced the levels of plasma histamine, IgE, and interleukin-4 in mouse model. Curcumenol inhibited IgE-BSA-stimulated β-hexosaminidase release and mast cell degranulation in a dose-dependent manner in BMMCs and RBL-2H3. Curcumenol also inhibited the activation of Src family tyrosine kinases (Fyn and Lyn) and the downstream spleen tyrosine kinase (Syk) in the FcεRI signaling pathway in BMMCs. Furthermore, curcumenol suppressed the activation of Akt, PLCγ1, and mitogen-activated protein kinase signaling. Molecular docking analysis revealed that curcumenol could bind to Fyn and Lyn kinases, thereby suppressing Src family tyrosine kinase signaling. This study suggests that curcumenol inhibits IgE-mediated allergic reactions by suppressing the activation Lyn and Fyn Src family kinases in OVA-challenged model animals. Therefore, curcumenol could be used as an effective alternative therapeutic for allergic diseases.

Keywords

Acknowledgement

This work was supported by the Korea Institute of Oriental Medicine, Ministry of Education, Science and Technology, Korea (Grant no. KSN1927331).

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