NYMC Faculty Publications

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

Mingzhuo Cao, Academy of Traditional Chinese Medicine Science, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, China.
Changda Liu, Academy of Traditional Chinese Medicine Science, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, China.
Kamal D. Srivastava, Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, New York, 10595, USA.
Adora Lin, Center for Cancer and Immunology Research, Children's National Research Institute, Washington, District of Columbia, 20010, USA.
Christopher Lazarski, Center for Cancer and Immunology Research, Children's National Research Institute, Washington, District of Columbia, 20010, USA.
Lu Wang, Center for Cancer and Immunology Research, Children's National Research Institute, Washington, District of Columbia, 20010, USA.
Anish Maskey, Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, New York, 10595, USA.
Ying Song, Academy of Traditional Chinese Medicine Science, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, China.
Xiaoke Chen, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, 10029, USA.
Nan Yang, Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, New York, 10595, USA.
Linda Zambrano, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, 10029, USA.
Renna Bushko, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, 10029, USA.
Anna Nowak-Wegrzyn, Allergy and Immunology, Department of Pediatrics, Hassenfeld Children's Hospital, New York University Grossman School of Medicine, New York, 10029, USA.
Amanda Cox, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, 10029, USA.
Zhigang Liu, Department of Immunology, the First Affiliated Hospital of Shen Zhen University, Shenzhen, 518116, China.
Weihua Huang, Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, New York, 10595, USA.
David Dunkin, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, 10029, USA.
Mingsan Miao, Academy of Traditional Chinese Medicine Science, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, China.
Xiu-Min Li, Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, New York, 10595, USA.

Author Type(s)

Faculty

Journal Title

Clinical and Experimental Allergy

First Page

250

Last Page

264

Document Type

Article

Publication Date

2-1-2022

Department

Pathology, Microbiology and Immunology

Second Department

Cell Biology and Anatomy

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.

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