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-alpha and IL-4 in RBL-2H3 cells.
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 beta-hexosaminidase release as a marker of degranulation in RBL-2H3 cells with IC(50) of 2.1 microM, followed by trimethylresveratrol (IC(50)=5.1 microM). Structural requirements of stilbenes for the activity are as follows: (1) The oxygen functions (-OCH(3), -OH), especially methoxyl groups, are essential and their positions on aromatic rings are important for the activity; (2) the alpha-beta 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>OCH(3) for the activity. Several active stilbenes (piceatannol, 3,5,4'-trimethylpiceatannol, resveratrol, trimethylresveratrol) also inhibited ionomycin-induced beta-hexosaminidase release, suggesting that inhibition of Ca(2+) influx or degranulation mechanisms after Ca(2+) influx is important for their activities. Piceatannol, 3,5,4'-trimethylpiceatannol, resveratrol, and trimethylresveratrol also significantly inhibited antigen-induced release of TNF-alpha and IL-4 in RBL-2H3 cells.
Matsuda
Hisashi
H
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Tewtrakul
Supinya
S
Morikawa
Toshio
T
Yoshikawa
Masayuki
M
D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000941:Antigens / Q000633:toxicity; D002417:Cattle; D015550:Cell Degranulation / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D012250:Rheum; D027343:Rhizome; D013267:Stilbenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018926:Anti-Allergic Agents; D000941:Antigens; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4