Anti-allergic activity of stilbenes from Korean rhubarb (Rheum undulatum L.): structure requirements for inhibition of antigen-induced degranulation and their effects on the release of TNF-α and IL-4 in RBL-2H3 cells

Abstract

Stilbenes isolated from the rhizomes of Rheum undulatum (Korean rhubarb) and the related compounds were investigated on their anti-allergic activities. The results revealed that 3,5,4′-trimethylpiceatannol exhibited the most potent inhibition against β-hexosaminidase release as a marker of degranulation in RBL-2H3 cells with IC50 of 2.1μM, followed by trimethylresveratrol (IC50=5.1μM). Structural requirements of stilbenes for the activity are as follows: (1) The oxygen functions (–OCH3, –OH), especially methoxyl groups, are essential and their positions on aromatic rings are important for the activity; (2) the α–β double bond increased the activity; (3) the glycoside moiety dramatically decreased the activity; and (4) the substitution group at the 3′-position in trimethylresveratrol (3,5,4′-trimethoxystilbene) was preferably OH>H>OCH3 for the activity. Several active stilbenes (piceatannol, 3,5,4′-trimethylpiceatannol, resveratrol, trimethylresveratrol) also inhibited ionomycin-induced β-hexosaminidase release, suggesting that inhibition of Ca2+ influx or degranulation mechanisms after Ca2+ influx is important for their activities. Piceatannol, 3,5,4′-trimethylpiceatannol, resveratrol, and trimethylresveratrol also significantly inhibited antigen-induced release of TNF-α and IL-4 in RBL-2H3 cells.