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The possible mechanisms of Picrasma quassiodes (D. Don) Benn. in the treatment of colitis induced by 2,4,6-trinitrobenzene sulfonic acid in mice
Authors:Wenna Zhao  Chen Sun  Jiao He  Lin Chen  Yongmin Zhang  Wenji Sun
Affiliation:1. Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi''an 710069, PR China;2. Institut Parisien de Chimie Moléculaire, UMR CNRS 7201, Université Pierre et Marie Curie-Paris 6, 4 place Jussieu, 75005 Paris, France
Abstract:

Ethnopharmacological relevance

Picrasma quassiodes (D. Don) Benn.(PQB) is used in folk medicines for the treatment of colds, upper respiratory infection, acute tonsillitis, acute gastroenteritis, bacillary dysentery and a variety of acute infectious diseases in Asia. Although recent reports indicate that PQB has antibacterial, and anti-inflammatory effects, its effects on colitis and its inhibitory mechanisms have not been previously reported.

Aim of the study

To assess the effects and the mode of action of the extract of Picrasma quassiodes (D. Don) Benn.(PQB) on a model of colitis in mice induced by trinitrobenzene sulfonic acid (TNBS).

Materials and methods

We induced mice colitis using TNBS/ethanol, then different doses of Picrasma quassiodes (D. Don) Benn.(PQB) extract (100, 200 and 400 mg/kg/day) and sulfasalazine (500 mg/kg/day) were administered by gavage for 7 days after the induction of colitis. The mice body weight, colonic wet weight, colonic lengths, myeloperoxidase (MPO) activity, macroscopic and histological colon injury were observed. Pro-inflammatory cytokines such as: tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were assayed by enzyme-linked immunoassay. The protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the colons were determined by immunohistochemical analysis.

Results

PQB administration effectively prevented mice diarrhea, decreasing of the body weights, shortening of colon length and increasing of colon wet weight. Macroscopic and histological examinations also indicated that it was protected against colonic edema, ulceration and MPO activity elevation. Furthermore, PQB inhibited the abnormal secretions of pro-inflammatory cytokines, such as TNF-α and IL-8. Additionally, administration of PQB effectively inhibited COX-2 and iNOS protein expression.

Conclusions

These results suggest that PQB has an anti-inflammatory effect on TNBS-induced colitis due to the down-regulations of the productions and expressions of inflammatory mediators, and that it may be a potential inflammatory bowel disease (IBD) drug candidate.
Keywords:PQB, Picrasma quassiodes (D. Don) Benn.   IBD, Inflammatory bowel disease   CD, Crohn's disease   UC, Ulcerative colitis   TNBS, Trinitrobenzene sulfonic acid   ANOVA, One-way analysis of variance   COX-2, Cyclooxygenase-2   ELISA, Enzyme-linked immunosorbent assay   IFN-α, Interferon-α   IL, Interleukin   iNOS, Inducible nitric oxide synthase   MPO, Myeloperoxidase   SASP, Sulfasalazine   SEM, Standard error of mean   TNF-α, Tumor necrosis factor-α   (NF-κ β), Nuclear factor kappa β   AP-1, Activator protein-1   H&  E, Hematoxylin and eosin   MDS, Macroscopic damage score   HDS, Histopathological damage score   S.D., Standard deviation
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