Intestinal anti-inflammatory effects of total alkaloid extract from Fumaria capreolata in the DNBS model of mice colitis and intestinal epithelial CMT93 cells

被引:33
作者
Bribi, Noureddine [1 ,2 ]
Algieri, Francesca [2 ]
Rodriguez-Nogales, Alba [2 ]
Vezza, Teresa [2 ]
Garrido-Mesa, Jose [2 ]
Pilar Utrilla, Maria [2 ]
del Mar Contreras, Maria [3 ,4 ]
Maiza, Fadila [1 ]
Segura-Carretero, Antonio [3 ,4 ]
Elena Rodriguez-Cabezas, Maria [2 ]
Galvez, Julio [2 ]
机构
[1] Univ Bejaia, Fac Sci Nat & Vie, Lab Biotechnol Vegetales & Ethnobot, Bejaia 06000, Algeria
[2] Univ Granada, Ctr Biomed Res CIBM, Ibs GRANADA, Dept Pharmacol,CIBER EHD, Ave Conocimiento S-N, Granada 18016, Spain
[3] Univ Granada, Fac Sci, Dept Analyt Chem, Ave Fuentenueva S-N, E-18071 Granada, Spain
[4] Res & Dev Ctr Funct Food CIDAF, Hlth Sci Technol Pk,Ave Conocimiento 37, Granada 18016, Spain
关键词
DNBS mouse colitis; Intestinal inflammation; Cytokine; Stylopine; protopine; Fumaria capreolata; ISOQUINOLINE ALKALOIDS; CHELIDONIUM-MAJUS; CYTOKINES; ARTICLE; ANTIOXIDANT; THERAPY; INNATE; L;
D O I
10.1016/j.phymed.2016.05.003
中图分类号
Q94 [植物学];
学科分类号
071001 [植物学];
摘要
Background: Fumaria capreolata L. (Papaveraceae) is a botanical drug used in North Africa for its gastrointestinal and anti-inflammatory properties. It is characterized for the presence of several alkaloids that could be responsible for some of its effects, including an immunomodulatory activity. Purpose: To test in vivo the intestinal anti-inflammatory properties of the total alkaloid fraction extracted from the aerial parts of F. capreolata (AFC), and to evaluate its effects on an intestinal epithelial cell line. Study design and methods: AFC was chemically characterized by liquid chromatography coupled to diode array detection and high resolution mass spectrometry. Different doses of AFC (25, 50 and 100 mg/kg) were assayed in the DNBS model of experimental colitis in mice, and the colonic damage was evaluated both histologically and biochemically. In addition, in vitro experiments were performed with this alkaloid fraction on the mouse intestinal epithelial cell line CMT93 stimulated with LPS. Results: The chemical analysis of AFC revealed the presence of 23 alkaloids, being the most abundants stylopine, protopine and coptisine. Oral administration of AFC produced a significant inhibition of the release and the expression of IL-6 and TNF-alpha in the colonic tissue. It also suppressed in vivo the transcription of other pro-inflammatory mediators such as IL-1 beta, iNOS, IL-12 and IL-17. Furthermore, AFC showed an immunomodulatory effect in vitro since it was able to inhibit the mRNA expression of IL-6, TNF-alpha and ICAM-1. Moreover, the beneficial effect of AFC in the colitic mice could also be associated with the normalization of the expression of MUC-2 and ZO-1, which are important for the intestinal epithelial integrity. Conclusion: The present study suggests that AFC, containing 1.3% of stylopine and 0.9% of protopine, significantly exerted intestinal anti-inflammatory effects in an experimental model of mouse colitis. This fact could be related to a modulation of the intestinal immune response and a restoration of the intestinal epithelial function. (C) 2016 Elsevier GmbH. All rights reserved.
引用
收藏
页码:901 / 913
页数:13
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