Alginic acid has anti-anaphylactic effects and inhibits inflammatory cytokine expression via suppression of nuclear factor-kappaB activation.
BACKGROUND
Alginic acid is comprised of complex polymerized polysaccharides, and can be chemically extracted from seaweed. Alginic acid has an inhibitory effect on histamine release, but its molecular mechanisms are not well understood.


OBJECTIVE
To investigate the effect of alginic acid on the mast cell-mediated anaphylactic and inflammatory reaction using in vivo and in vitro models and elucidate its molecular mechanisms.


METHODS
The effect of alginic acid on an allergy model was analysed by anaphylaxis, a histidine decarboxylase (HDC) assay, and a histamine assay. Cytokine production was analysed by means of ELISA. Cytokine expression was analysed by means of RT-PCR, and Western blotting. Transcription factor activity was analysed by a luciferase assay and a transcription factor-enzyme linked immunoassay.


RESULTS
Alginic acid dose dependently inhibited compound 48/80-induced systemic anaphylaxis with doses of 0.25-1 g/kg 1 h (P<0.01, n=6) and significantly inhibited passive cutaneous anaphylaxis by 54.8%. Alginic acid (0.01-1 microg/mL) inhibited histamine release from serum and peritoneal mast cells (P<0.01). All these effects were stronger than those of disodium cromoglycate (DSCG), the reference drug tested. Alginic acid also inhibited HDC expression and activity on the phorbol myristate acetate (PMA)+A23187-stimulated human mast cell line, HMC-1 cells. Moreover, alginic acid significantly inhibited the production of PMA+A23187-induced inflammatory cytokines, IL-1beta and TNF-alpha, but not that of IL-6 or IL-8. In activated HMC-1 cells, the expression level of nuclear factor (NF)-kappaB/Rel A protein increased in the nucleus, whereas the level of NF-kappaB/Rel A in the nucleus was decreased by alginic acid treatment. In addition, alginic acid (0.01 microg/mL) decreased the PMA+A23187-induced luciferase activity and DNA-binding activity.


CONCLUSIONS
The present results indicate that alginic acid has potent anti-anaphylactic and anti-inflammatory properties.
Jeong
H-J
HJ
College of Pharmacy, VestibuloCochlear Research Center of Wonkwang University, Iksan Jeonbuk, Korea.
Lee
S-A
SA
Moon
P-D
PD
Na
H-J
HJ
Park
R-K
RK
Um
J-Y
JY
Kim
H-M
HM
Hong
S-H
SH
D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D000001:Calcimycin; D002460:Cell Line; D016207:Cytokines / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D006636:Histamine Release; D006640:Histidine Decarboxylase / Q000032:analysis / Q000378:metabolism; D007476:Ionophores; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism*; D010323:Passive Cutaneous Anaphylaxis; D010537:Peritoneum; D051381:Rats; D017208:Rats, Wistar; D012882:Skin Tests; D013755:Tetradecanoylphorbol Acetate; D003189:p-Methoxy-N-methylphenethylamine
D000464:Alginates; D018926:Anti-Allergic Agents; D016207:Cytokines; D006603:Hexuronic Acids; D007476:Ionophores; D016328:NF-kappa B; D000001:Calcimycin; D003189:p-Methoxy-N-methylphenethylamine; D020723:Glucuronic Acid; D006640:Histidine Decarboxylase; D013755:Tetradecanoylphorbol Acetate