No abstract

The aim of the present study was to investigate the therapeutic effect and mechanism of proanthocyanidins from grape seed (GSPE) in the treatment of recurrent ulcerative colitis (UC) in rats. To induce recurrent colitis, rats were instilled with 2,4,6-trinitrobenzenesulfonic acid (TNBS) (80 mg/kg) into the colon through the cannula in the first induced phase, and then the rats were instilled a second time with TNBS (30 mg/kg) into the colon on the sixteenth day after the first induction UC. Rats were intragastrically administered GSPE (200 mg/kg) per day for 7 days after twice-induced colitis by TNBS. Sulfasalazine at 500 mg/kg was used as a positive control drug. Rats were killed 7 days after GSPE treatment. The colonic injury and inflammation were assessed by macroscopic and macroscopic damage scores, colon weight/length ratio (mg/cm), and myeloperoxidase activity. Then, superoxide dismutase, glutathione peroxidase, inducible nitric oxide synthase (iNOS) activities, and the levels of malonyldialdehyde, glutathione, and nitric oxide in serum and colonic tissues were measured. Compared with the recurrent UC group, GSPE treatment facilitated recovery of pathologic changes in the colon after induction of recurrent colitis, as demonstrated by reduced colonic weight/length ratio and macroscopic and microscopic damage scores. The myeloperoxidase and iNOS activities with malonyldialdehyde and nitric oxide levels in serum and colon tissues of colitis rats were significantly decreased in the GSPE group compared with those in the recurrent UC group. In addition, GSPE treatment was associated with notably increased superoxide dismutase, glutathione peroxidase activities, and glutathione levels of colon tissues and serum of rats. GSPE exerted a protective effect on recurrent colitis in rats by modifying the inflammatory response, inhibiting inflammatory cell infiltration and antioxidation damage, promoting damaged tissue repair to improve colonic oxidative stress, and inhibiting colonic iNOS activity to reduce the production of nitric oxide.

To elucidate the molecular mechanisms involved in the therapeutic effects of proanthocyanidins from grape seeds (GSPE), we explore whether GSPE regulates the inflammatory response of TNBS-induced colitis in rats at the levels of NF-κB signal transduction pathway. Rats were intragastrically administered of different doses of GSPE (100, 200 and 400 mg·kg−1) per day for seven days after ulcerative colitis (UC) was induced by intracolonic injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Sulfasalazine (SASP) at 400 mg/kg was used as a positive control drug. The expression of nuclear factor-kappa B (NF-κB), phospho-I kappaB-alpha (pIκBα), inhibitor kappa B kinase (IκK) in the colon tissues were all measured by enzyme-linked immunosorbent assay (ELISA) methods. Treatment with GSPE reduced the expression of NF-κB, pIκBα and IκK in the colon. The results of this study show that GSPE exerts beneficial effects in inflammatory bowel disease by inhibition of NF-κB signal transduction pathways.

No abstract

No abstract

Ulcerative colitis (UC) is characterized by oxidative and nitrosative stress and neutrophil infiltration. In the present study, we aimed to investigate the therapeutic effect of ginsenoside Rd (GRd) in rats with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced recurrent UC. After UC was twice-induced by intracolonic injection of TNBS, rats were intragastrically administered different doses of GRd per day for 7 days. The colonic lesions and inflammation were evaluated both histologically and biochemically. Compared with the TNBS group, GRd treatment facilitated recovery of pathologic changes in the colon after induction of recurrent UC, as evidenced by a significant reduction of colonic weight/length ratio and macroscopic and microscopic damage scores (p < 0.01). The myeloperoxidase and inducible nitric oxide synthase activities with malonyldialdehyde and nitric oxide levels in colonic tissues were significantly decreased in the GRd group compared with those in the TNBS group (p < 0.01). GRd treatment was associated with remarkably increased superoxide dismutase and glutathione peroxidase activities. Results showed a valuable effect of GRd against TNBS-induced recurrent UC by inhibiting neutrophil infiltration and promoting the antioxidant capacity of the damaged colonic tissue.

Our and other studies have reported that homocysteine thiolactone (HTL) could induce endothelial dysfunction. However, the precise mechanism was largely unknown. In this study, we tested the most possible factor-endoplasmic reticulum (ER) stress, which was demonstrated to be involved in endothelial dysfunction in cardiovascular disease. Acetylcholine (Ach)-induced endothelium-dependent relaxation (EDR) and biochemical parameters were measured in rat isolated aorta. The level of reactive oxygen species (ROS) and NO was designed by specific fluorescent probe DCFH-DA and DAF-FM DA separately. The nuclear translocation of the NF-κB was studied by immune-fluorescence. The mRNA expression and protein expression of GRP78--a key indicator for the induction of ER stress--were assessed by real-time PCR and Western blot. Two ER stress inhibitors-4-PBA (5 mm) and Tudca (500 μg/mL)--significantly prevented HTL-impaired EDR and increased NO release, endothelial nitric oxide synthase (eNOS) and SOD activity, decreased ROS production, NADPH activity, NOX-4 mRNA and MDA level. We also found that 4-PBA and Tudca blocked HTL--induced NF-κB activation thus inhibiting the downstream target gene production including TNF-α and ICAM-1. Simultaneously, HTL increased the mRNA and protein level of GRP78. HTL could induce ER stress leading to a downstream enhancement of oxidative stress and inflammation, which finally caused vascular endothelial dysfunction.

No abstract