Inhibitory effects of Diospyros kaki in a model of allergic inflammation: role of cAMP, calcium and nuclear factor-κB.
Diospyros kaki (D. kaki) has been cultivated throughout Eastern Asia for hundreds of years. D. kaki contains various biological active compounds, such as amino acids, carotenoids, ﬂavonoids, tannins, catechins and vitamin A. Previous studies have shown that D. kaki has beneficial effects on homeostasis, constipation, hypertension, atherosclerosis and allergic dermatitis and is a good source of antioxidants, polyphenols and dietary ﬁber. However, the anti-allergic and anti-inflammatory effects of D. kaki have not yet been elucidated. This study aimed to investigate the protective effects of the aqueous extract of Diospyros kaki (AEDK) on mast cell-mediated allergic inflammation and to determine its possible mechanisms of action by using in vitro and in vivo mast cell-based models. The cAMP and intracellular calcium levels were measured to clarify the mechanisms by which AEDK inhibits the release of histamine from mast cells. AEDK inhibited the release of histamine and β-hexosaminidase from mast cells by modulating cAMP and intracellular calcium levels. We also measured the expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. AEDK decreased gene expression and the secretion of the pro-inflammatory cytokines, TNF-α and IL-1β by inhibiting nuclear factor-κB. In addition, AEDK inhibited systemic and cutaneous allergic reaction. The inhibitory effects of AEDK on allergic reaction and the release of histamine were found to be similar to those of disodium cromoglycate, a known anti-allergic drug. To isolate the active component of AEDK, activity-guided fractionation was performed, based on the inhibitory effects on systemic anaphylaxis. Catechin was identified as an active compound. The present findings provide evidence that AEDK inhibits allergic inflammation and suggest the therapeutic application of AEDK in allergic inflammatory disorders.
Korea Traditional Medicine Agency, Korea Promotion Institute for Traditional Medicine Industry, Gyeongsan 712‑210, Republic of Korea.
Hui-Hun
HH
Kim
Duk-Sil
DS
Kim
Sung-Wan
SW
Kim
Se-Hyun
SH
Lim
Dae Keun
DK
Kim
Tae-Yong
TY
Shin
Sang-Hyun
SH
Kim
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004205:Cromolyn Sodium / Q000494:pharmacology; D029788:Diospyros / Q000737:chemistry*; D004195:Disease Models, Animal; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D018927:Anti-Asthmatic Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D004205:Cromolyn Sodium; D002118:Calcium