Comparative study on the alleviating effect of neohesperidin dihydrochalcones and its synthetic precursor neohesperidin on ovalbumin-induced food allergy.

The biological activities of natural flavonoids are structure-dependent. To investigate the structure-dependent activities of neohesperidin dihydrochalcone (NHDC) and neohesperidin (NH), which have the same basic skeletal structure, we systematically compared their roles in alleviating ovalbumin-induced food allergies in mice. Our results indicate that NHDC is superior to NH in ameliorating allergic symptoms, especially in restoring T helper 1 and T helper 2 cells (Th1 and Th2, respectively)balance and inhibiting splenic NOTCH/nuclear factor kappa-B (NF-κB) activation by enhancing binding to Hes1, which was validated by molecular docking. Both compounds increased the abundance of beneficial gut microbiota (e.g., Lactobacillus). Still, the dihydrochalcone portion of NHDC possessed superior intestinal barrier repair and immunomodulatory effects, synergizing anti-inflammatory and microbiota modulatory effects. These results provide new insights into the structure-dependent activity of natural flavonoids in treating food allergies.