Sesamin is an effective spleen tyrosine kinase inhibitor against IgE-mediated food allergy in computational,cell-based and animal studies  

作　　者：Yu Li Xuerui Chen Longhua Xu Xintong Tan Dapeng Li Dongxiao Sun-Waterhouse Feng Li 

机构地区：[1]College of Food Science and Engineering,Shandong Agricultural University,Tai’an 271018,China [2]Key Laboratory of Food Nutrition and Human Health in Universities of Shandong,Tai’an 271018,China [3]School of Chemical Sciences,The University of Auckland,Auckland 1142,New Zealand

出　　处：《Food Science and Human Wellness》2025年第2期469-483,共15页食品科学与人类健康(英文)

基　　金：Incubation Program of Youth Innovation in Shandong Province;Key Research and Development Program of Shandong Province(2021TZXD007)。

摘　　要：Food allergy has become a global concern.Spleen tyrosine kinase(SYK)inhibitors are promising therapeutics against allergic disorders.In this study,a total of 300 natural phenolic compounds were firstly subjected to virtual screening.Sesamin and its metabolites,sesamin monocatechol(SC-1)and sesamin dicatechol(SC-2),were identified as potential SYK inhibitors,showing high binding affinity and inhibition efficiency towards SYK.Compared with R406(a traditional SYK inhibitor),sesamin,SC-1,and SC-2 had lower binding energy and inhibition constant(Ki)during molecular docking,exhibited higher bioavailability,safety,metabolism/clearance rate,and distribution uniformity ADMET predictions,and showed high stability in occupying the ATP-binding pocket of SYK during molecular dynamics simulations.In anti-dinitrophenyl-immunoglobulin E(Anti-DNP-Ig E)/dinitrophenyl-human serum albumin(DNP-HSA)-stimulated rat basophilic leukemia(RBL-2H3)cells,sesamin in the concentration range of 5-80μmol/L influenced significantly the degranulation and cytokine release,with 54.00%inhibition againstβ-hexosaminidase release and 58.45%decrease in histamine.In BALB/c mice,sesamin could ameliorate Anti-DNP-Ig E/DNP-HSA-induced passive cutaneous anaphylaxis(PCA)and ovalbumin(OVA)-induced active systemic anaphylaxis(ASA)reactions,reduce the levels of allergic mediators(immunoglobulins and pro-inflammatory cytokines),partially correct the imbalance of T helper(Th)cells differentiation in the spleen,and inhibit the phosphorylation of SYK and its downstream signaling proteins,including p38 mitogen-activated protein kinases(p38 MAPK),extracellular signalregulated kinases(ERK),and p65 nuclear factor-κB(p65 NF-κB)in the spleen.Thus,sesamin may be a safe and versatile SYK inhibitor that can alleviate Ig E-mediated food allergies.

关 键 词：Food allergy Spleen tyrosine kinase SESAMIN Computational tools RBL-2H3 cells BALB/c mice 

分 类 号：R73[医药卫生—肿瘤]