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Life Sci ; 239: 117021, 2019 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-31678552

RESUMEN

OBJECTIVES: Clematichinenoside AR (AR) is a saponin extracted for traditional Chinese medicine with the effects of improving the expression of tight junction (TJ) proteins and mediating anti-inflammatory activities. However, its effect on Crohn's disease (CD) is still unknown. We aimed to investigate the impact of AR on CD-like colitis and determine the mechanism underlying its effects. METHODS: Interleukin-10 gene knockout (Il-10-/-) mice (male, fifteen weeks old) with spontaneous colitis were allocated to the positive control and AR-treated (32 mg/kg AR administered every other day by gavage for 4 weeks) groups. Wild-type (WT) mice (male, fifteen weeks old) composed the negative control group. The effects of AR on intestinal barrier function and structure and T cell responses as well as the potential mechanisms underlying these effects were investigated. RESULTS: AR treatment significantly improved spontaneous colitis in Il-10-/- mice as demonstrated by reductions in the inflammatory score, disease activity index (DAI) and levels of inflammatory factors. The effects of AR on colitis in Il-10-/- mice were related to protecting intestinal barrier function and maintaining immune system homeostasis (regulatory T cell (Treg)/T helper 17 (Th17) cell balance). The anticolitis effect of AR may partly act by downregulating PI3K/Akt signaling. CONCLUSIONS: AR may have therapeutic potential for treating CD in humans.


Asunto(s)
Colitis/tratamiento farmacológico , Colitis/genética , Interleucina-10/genética , Intestinos/patología , Saponinas/uso terapéutico , Triterpenos/uso terapéutico , Animales , Traslocación Bacteriana/efectos de los fármacos , Colitis/patología , Citocinas/metabolismo , Intestinos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Linfocitos T Reguladores/efectos de los fármacos
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