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Anti-IgE Effect of Small-Molecule-Compound Arctigenin on Food Allergy in association with a Distinct Transcriptome Profile

Ming Zhuo, C;Liu, C;Srivastava, KD;Lin, A;Lazarski, C;Wang, L;Maskey, A;Song, Y;Chen, X;Yang, N;Zambrano, L;Bushko, R;Nowak-Wegrzyn, A;Cox, A;Liu, Z;Huang, W;Dunkin, D;Miao, M;Li, XM;

Excessive production of IgE plays a major role in the pathology of food allergy. In an attempt to identify anti-IgE natural products, Arctium Lappa was one of the most effective herbs among approximately 300 screened medicinal herbs. However, little is known about its anti-IgE compounds.To identify compounds from Arctium Lappa for targeted therapy on IgE production and explore their underlying mechanisms.Liquid-liquid extraction and column chromatographic methods were used to purify the compounds. IgE inhibitory effects were determined on IgE producing human myeloma U266 cells, peanut-allergic murine model, and PBMCs from food-allergic patients. Genes involved in IgE inhibition in PBMCs were studied by RNA sequencing.The main compounds isolated were identified as arctiin and arctigenin. Both compounds significantly inhibited IgE production in U266 cells, with arctigenin the most potent (IC50=5.09?g/mL). Arctigenin (at a dose of 13.3 mg/kg) markedly reduced peanut-specific IgE levels, blocked hypothermia and histamine release in a peanut-allergic mouse model. Arctigenin also significantly reduced IgE production and Th2 cytokines (IL5, IL13) by PBMCs. We found 479 differentially expressed genes in PBMCs with arctigenin treatment (p<0.001 and fold-change ?1.5), involving 24 gene ontology terms (p<0.001, FDR <0.05); cell division was the most significant. Eleven genes including UBE2C and BCL6 were validated by qPCR.Arctigenin markedly inhibited IgE production in U266 cells, peanut allergic murine model and PBMCs from allergic patients by down-regulating cell division, cell cycle-related genes and up-regulating anti-inflammatory factors.This article is protected by