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 foodallergic 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 | 251 CAO et Al.
| INTRODUC TI ONFood allergy (FA) is a significant, worsening global public health issue. Over 2 decades, paediatric and adult incidence has increased dramatically in developed and some developing countries. 1-3 Foodinduced reactions account for 81% of paediatric anaphylaxis cases. 4 Despite worldwide prevalence, FA lacks sufficient therapies. Food avoidance and emergency injectable epinephrine remain the major standard of care, although the first FDA treatment, Palforzia ® , an oral immunotherapy for peanut allergy, was approved in January 2020. Food restriction, social isolation, fear and anxiety, particularly among teens, 5-7 present complex familial and social challenges. [8][9][10][11] 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, peanutallergic murine model and PBMCs from allergic patients by down-regulating cell division, cell cycle-related genes and up-regulating anti-inflammatory factors.