Anti-IgE effect of small-molecule-compound arctigenin on food allergy in association with a distinct transcriptome profile

Mingzhuo Cao, Changda Liu, Kamal D. Srivastava, Adora Lin, Christopher Lazarski, Lu Wang, Anish Maskey, Ying Song, Xiaoke Chen, Nan Yang, Linda Zambrano, Renna Bushko, Anna Nowak-Wegrzyn, Amanda Cox, Zhigang Liu, Weihua Huang, David Dunkin, Mingsan Miao, Xiu Min Li

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: 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. Objective: To identify compounds from Arctium Lappa for targeted therapy on IgE production and explore their underlying mechanisms. Methods: 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. Results: 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=5.09μg/mL). Arctigenin (at a dose of 13 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 (IL-5, IL-13) by PBMCs. We found 479 differentially expressed genes in PBMCs with arctigenin treatment (p <.001 and fold‑change ≥1.5), involving 24 gene ontology terms (p <.001, FDR <0.05); cell division was the most significant. Eleven genes including UBE2C and BCL6 were validated by qPCR. Conclusion: 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.

Original languageEnglish
Pages (from-to)250-264
Number of pages15
JournalClinical and Experimental Allergy
Volume52
Issue number2
DOIs
StatePublished - Feb 2022

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