Curcumin is a yellow dye in the crude drug "Turmeric" (Curcumae Rhizoma) from the rhizome of Curcuma longa L. (Zingiberaceae). Curcumin is reported to have anti-inflammatory, 1) anti-oxidative, 2) liver protective, 3) anti-spastic 4) and anti-tumor effects. 5) We reported that curcumin had an antiallergic effect using the type I and IV allergy model animals 6) and also that curcumin had an inhibitory effect on histamine release from rat peritoneal mast cells. 7)Several curcumin-related compounds occur in plants or biometabolites. Curcuminoids such as curcumin, monodemethoxycurcumin and bis-demethoxycurcumin are contained in the crude drug "Turmeric".2) Tetrahydrocurcumin (THC) is known to be an active metabolite of curcumin. 8,9) Curcuminoids are pharmacologically active agents of the crude drug "Turmeric" for multiple pharmacological activities.10) However, few, if any, reports have so far been concerned with which action of curcuminoids may be fundamental for exerting a variety of actions. Therefore, we focused our attention on the anti-oxidative and anti-allergic activities of curcumin-related compounds in order to see if the anti-allergic activities originate in anti-oxidative activities. Furthermore, we were very interested in the chemical features of curcumin or THC for exerting the anti-oxidative and anti-allergic activities.In the present study, we investigated anti-allergic and antioxidative effects of curcumin-related compounds (glycosides, reductants and bis-demethoxy analogs) in order to elucidate the chemical structural features of curcumin. The anti-allergic activities were assessed by measurement of histamine release from rat basophilic leukemia (RBL-2H3) cells. The anti-oxidative activities were evaluated by measurement of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals in cell-free solution and superoxide anion in cells. Finally, we discussed the underlying mechanisms on anti-allergic activities of curcumin-related compounds with special reference to their anti-oxidative activities. MATERIALS AND METHODSMaterials Curcumin, concanavalin A (Con A) and phosphatidyl serine were purchased from Sigma Japan Co. (Tokyo, Japan). Histamine · 2HCl, 2,2-diphenyl-1-picrylhydrazyl (DPPH), phorbol-12-myristate-13-acetate (PMA), cytochrome c (from bovine heart), superoxide dismutase (SOD) and o-phthalaldehyde were purchased from Wako Pure Chemical Co. (Osaka, Japan). Calcium ionophore A23187 was purchased from Calbiochem Co. (CA, U.S.A.).0.05% BSA-Tyrode buffer (pH 7.4) was prepared in distilled water and consisted of NaCl (137 mM), KCl (2.7 mM), N-(2-hydroxyethyl)piperazine-NЈ-ethanesulfonic acid (HEPES) (10 mM), glucose (5.6 mM), CaCl 2 (1.0 mM), MgCl 2 (1.0 mM), NaH 2 PO 4 · 2H 2 O (0.4 mM) and bovine serum albumin (BSA) (0.05%). Phosphate buffer saline (PBS) (pH 6.8) was prepared in distilled water and consisted of NaCl (137 mM), KCl (2.7 mM), Na 2 HPO 4 · 12H 2 O (8.0 mM) and KH 2 PO 4 (1.5 mM). Preparation of Curcumin-Related CompoundsWe prepared fifteen curcumin-related compounds by chemical modification o...