ABSTRACT
2-O-Alkyl-l-ascorbic acids and 3-O-alkyl-l-ascorbic acids were synthesized, and their degranulation inhibitory activities were evaluated. Among ascorbic acid derivatives with butyl, octyl, dodecyl, hexadecyl, and octadecyl groups introduced at the C-2 or C-3 positions, an AA derivative with a dodecyl group introduced at the C-3 position, 3-O-dodecyl-l-ascorbic acid (compound 8), showed the strongest inhibitory activity against antigen-stimulated degranulation. Compound 8 also inhibited calcium ionophore-stimulated degranulation. Compound 11, in which the hydroxyl group at the C-6 position of compound 8 was substituted with an amino group, and compound 12, in which the dodecyloxy group at the C-3 position of compound 8 was exchanged with a dodecylamino group, were synthesized, and these derivatives showed weaker inhibitory activity against antigen-stimulated degranulation than that of compound 8. In addition, orally administered compound 8 inhibited passive cutaneous anaphylaxis reactions in mice with a potency equal to that of oxatomide, an antiallergic agent. These results suggest that compound 8 may be a candidate for antiallergic treatment.
Subject(s)
Anti-Allergic Agents , Animals , Mice , Anti-Allergic Agents/pharmacology , Ascorbic Acid/pharmacologySubject(s)
Anaphylaxis , Anaphylaxis/diagnosis , Anaphylaxis/etiology , Animals , Mice , Mice, Inbred C57BL , Reward , Ventral Tegmental AreaABSTRACT
Aim To investigate the mechanism of achyranthes bidentata polysaccharides on degranulation of mast cells. Methods The experiment of passive cutaneous anaphylaxis was used to determine the effect of achyranthes bidentata polysaccharides on degranulation of mast cells in vivo. For in vitro study, various doses of achyranthes bidentata polysaccharides were added to the culture medium of sensitized RBL-2H3 cells. The antigen-induced release of degranulation was measured by enzymatic assay, histamine by EIA and cytokines by ELISA. In addition, the activation of Akt and p38 were measured by Western blot. Results Treatment with achyranthes bidentata polysaccharides was followed by a decrease in PCA of rats and ?-hexosaminidase, histamine, TNF-?,IL-4,Akt and p38 of RBL-2H3 cells induced by antigen. Conclusions Achyranthes bidentata polysaccharides might suppress the anaphylactic reaction through inhibition of action of mast cells. Akt and p38 contributed at least in part to this event.
ABSTRACT
AIM:To investigate the mechanism of Maxing Shigan Decoction(Herba ephedrae,Semen armeniacae amarum,Radix er Rhizoma glycyrrhizae,Gypsum fibrosum) against type Ⅰ hypersenstivity reaction. METHODS: The experiment of passive cutaneous anaphylaxis(PCA) was used to determine the effect of Maxing Shigan Decoction on degranulation of mast cells in vivo.For in vitro study,the drug serum of Maxing Shigan Decoction was added to the culture medium of sensitized RBL-2H3 cells.The antigen-induced release of degranulation was measured by enzymatic assay,histamine by enzyme immunoassay(EIA) and cytokines by enzyme-linked immunosorbent assay(ELISA). RESULTS: The results showed that treatment with drug serum of Maxing Shigan Decoction was followed by a decrease in PCA of rats and in degranulation,histamine,TNF-? and IL-4 from RBL-2H3 cells induced by antigen. CONCLUSION: Maxing Shigan Decoction may suppress the type Ⅰ hypersensitivity reaction by inhibiting the action of mast cells.
