Anti-allergic principles from Thai zedoary: structural requirements of curcuminoids for inhibition of degranulation and effect on the release of TNF-alpha 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, tetrahydrodemethoxycurcumin, 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 IC(50) of 5.3 microM, followed by bisdemethoxycurcumin (IC(50) = 11 microM). 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.
Matsuda
Hisashi
H
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Tewtrakul
Supinya
S
Morikawa
Toshio
T
Nakamura
Akihiko
A
Yoshikawa
Masayuki
M
D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D030024:Curcuma; D003474:Curcumin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D027343:Rhizome; D013785:Thailand; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018926:Anti-Allergic Agents; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D003474:Curcumin