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1.
Gut and Liver ; : 406-411, 2016.
Artigo em Inglês | WPRIM | ID: wpr-155142

RESUMO

BACKGROUND/AIMS: DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. METHODS: Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. RESULTS: The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. CONCLUSIONS: DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.


Assuntos
Animais , Ratos , Western Blotting , Dextranos , Fluoresceína , Indometacina , Inflamação , Intestino Delgado , Sistema de Sinalização das MAP Quinases , Permeabilidade , Fosfotransferases
2.
The Korean Journal of Physiology and Pharmacology ; : 89-94, 2014.
Artigo em Inglês | WPRIM | ID: wpr-727590

RESUMO

DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces Ca2+ signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in Ca2+ signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated Ca2+-activated Cl- channels (CaCCs) and increased intracellular calcium concentrations ([Ca2+]i) in primary cultured human conjunctival cells. DA-6034 also increased [Ca2+]i in mouse salivary gland cells and human corneal epithelial cells. [Ca2+]i increase of DA-6034 was dependent on the Ca2+ entry from extracellular and Ca2+ release from internal Ca2+ stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate (IP3) pathway and lysosomal Ca2+ stores. These results suggest that DA-6034 induces Ca2+ signaling via extracellular Ca2+ entry and RyRs-sensitive Ca2+ release from internal Ca2+ stores in epithelial cells.


Assuntos
Animais , Humanos , Camundongos , Ratos , Cálcio , Sinalização do Cálcio , Células Epiteliais , Mucosa Gástrica , Glicoproteínas , Fosfolipases , Canal de Liberação de Cálcio do Receptor de Rianodina , Glândulas Salivares , Doadores de Tecidos
3.
Korean Journal of Medicine ; : 302-309, 1998.
Artigo em Coreano | WPRIM | ID: wpr-39941

RESUMO

OBJECTIVE: In traditional medicine, Artemisia capillaris has been used for treatment of chronic diarrhea. Previously we found Artemisia capillaris had an effect on rats with TNBS-induced colitis. Eupatilin, a kind of flavonoids, may be a probable effective component. To evaluate the effect of a eupatilin derivative compound DA-6034 on the rat with TNBS-induced colitis, we perfomed this study. METHODS: Colitis was induced with 1ml of 50 mg/ml TNBS mixed with 60 % ethanol (vol/vol) in Sprague- Dawley rats. From the next day, 1ml methylcellulose, 1 mg/kg prednisolone, 0.3 or 3 mg/kg of DA-6017 and DA-6034 were administered through rectum once daily for 2 weeks. At 2days, 1week, and 2weeks later, we evaluated the effect by gross damage score (0-10) and measured myeloperoxidase, PGE2, and LTB4 from the damaged mucosa. RESULTS: The mean gross damage scores of prednisolone and 3 mg/kg of DA-6034 groups were significantly lower than that of a placebo group at 2weeks (0.8, 0.9 vs. 4.0, p<0.05). Myeloperoxidase activities also seemed to be lower in those effective groups but were not statistically significant. LTB4 levels were lower in prednisolone and, 0.3 and 3 mg/kg of DA-6034 groups than in a placebo group at 2weeks (7.91, 7.23, and 7.13 vs. 13.90 ng/mg protein, p<0.05). PGE2 levels were decreased in prednisolone and 0.3 mg/kg of DA-6034 groups at 2days. DA-6017 showed no effects. CONCLUSIONS: Eupatilin derivative compound, DA- 6034 was effective in rats with TNBS-induced colitis. In that LTB4 level is lowered with some decrease of PGE2 level, this agent probably has an inhibitory effect on arachidonic acid metabolism.


Assuntos
Animais , Ratos , Ácido Araquidônico , Artemisia , Colite , Diarreia , Dinoprostona , Etanol , Flavonoides , Leucotrieno B4 , Medicina Tradicional , Metabolismo , Metilcelulose , Mucosa , Peroxidase , Prednisolona , Reto
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