Anti-allergic principles from Thai zedoary:: structural requirements of curcuminoids for inhibition of degranulation and effect on the release of TNF-α and IL-4 in RBL-2H3 cells

The 80% aqueous acetone extract of the rhizomes of Curcuma zedoaria cultivated in Thailand (Thai zedoary) was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation, in RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice. From the active fraction, four curcuminoids (curcumin, dihydrocurcumin, tetra-hydrodemethoxycurcumin, and tetrahydrobisdemethoxycurcumin) were isolated together with two bisabolane-type sesquiterpenes, and the effects of four curcuminoids from Thai zedoary and several related compounds on the degranulation were examined. Among them, curcumin showed the highest activity against beta-hexosaminidase release with IC50 of 5.3 hM, followed by bisdemethoxycurcumin (IC50 = 11muM). With regard to the structural requirements of curcuminoids for the activity, the conjugated olefins at the 1-7 positions and the 4'- or 4"-hydroxyl groups of curcuminoids were suggested to be essential for the strong activity, whereas the 3'- or 3"-methoxyl group only enhanced the activity. Furthermore, effects of curcumin and bisdemethoxycurcumin on calcium ionophores (A23187 and ionomycin)-induced degranulation and antigen-induced release of TNF-alpha and IL-4 were examined. (C) 2004 Elsevier Ltd. All rights reserved.