Anti-IgE Effect of Small-Molecule-Compound Arctigenin on Food Allergy in Association With a Distinct Transcriptome Profile
Pathology, Microbiology & Immunology
Cell Biology and Anatomy
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.
Cao, M., Liu, C., Srivastava, K. D., 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, X. (2022). Anti-IgE Effect of Small-Molecule-Compound Arctigenin on Food Allergy in Association With a Distinct Transcriptome Profile. https://doi.org/10.1111/cea.14048