The Effect Of 50% Ethanolic Extract Of Apple Polyphenols Against Ulcerative Colitis And Its Mechanism

Objective: Inflammatory bowel disease(IBD), clinical manifestation to bloody diarrhea, abdominal cramps and pain, is a kind of immune mediated the influence of the intestinal mucosa of easy relapse of chronic disease. IBD patients, compared with the general population, but also a higher susceptibility to colorectal cancer. Crohn’s disease(CD) and ulcerative colitis, ulcerative colitis, UC) is the most common inflammatory bowel disease in two forms.The pathological changes of ulcerative colitis is wide and condition again and again, and the exact pathogenesis is not clear, so for the treatment of ulcerative colitis is difficult at present. Modern medicine includes mainly5-aminosalicylic acid, steroids and immunosuppressant drug treatment. However, 5-aminosalicylic acid are class specific anti-inflammatory drugs, for ulcerative colitis can only have the effect of control and temporarily relieve symptoms, not radically cure diseases and having a headache after taking the drug, renal toxic side effects, such as disease easily repeated after drug withdrawal. Apple can reduce certain types of cancer, cardiovascular disease, asthma, diabetes risk of the disease. Apple polyphenols in apple extract contains several kinds of flavonoids and certain plant chemicals, including quercetin glycosides, catechin and epicatechin, procyanidins, cornflower galactose glucoside, coumaric acid, chlorogenic acid, gallic acid and root bark. The experimental observation of apple polyphenols 50% ethanol extract(AP50E) of dextran sodium sulfate(DSS) induction of the therapeutic effect of ulcerative colitis in mice and its mechanism of action of the preliminary inquiry, for the development and utilization of health food of the new-type ulcerative colitis or provides the reference for the development of therapeutic drugs.Method: UC was induced by dextran sulfate sodium(DSS) at concentration of 2.5% in mice. Mice were intragastrically administrated of different doses of AP50E(300mg/kg and 600mg/kg) per day for 7 days. Olsalazine at 500mg/kg was used as a positive control drug. Mouse’s weight, food intake and water intake were recorded after 7 days of treatment. After 7 days, the animals were killed, and the following parameters were assessed: colon length, morphological score, histological score and biochemical assay of(MDA), myeloperoxidase(MPO), interleukin-10(IL-10) and tumor necrosis factor-α(TNF-α). Adding phorbol 12-myristate 13-acetate(PMA) or AP50 E into Caco-2 cells for 12 h, interleukin-12(IL-12) content of the culture medium were measured by ELISA and the content of Akt were measured by Western-Blot method.Result:1 After one week treatment, compared with other group, the water intake of DSS control group has increased notably. The food intake has not a notable difference between every group except normal control group.2 Compared with the DSS control group, AP50 E treatment group have a lower degree of weights decrease.3 DSS control group have a significant degree of colonic shortening, while AP50 E treatment group have lower degree.4 After the determination of colons weights, we found AP50 E treatment could protect mice to against the UC.5 The treatment of AP50 E could reduce the colonic macroscopic and microscopic damage.6 Compared with the DSS control group, the content of MDA in AP50 E treatment group(600mg/kg) have a significant decrease.7 Serum TNF-α content in the model group was significantly increased, and serum IL-10 content decreased significantly. The content of TNF-α reduced, as well IL-10 content increased significantly after AP50 E intervention.8 Colonic MPO activity increased obviously in the model mice, and AP50 E intervention obviously improved; AP50 E also inhibited the expression of COX-2 in colon mucosa cells.9 AP50 E has a protective effect on the apoptosis induced by PMA in Caco-2 cells. AP50 E against apoptosis may due to the up regulation of Akt protein expression.10 The induction of PMA can make the elevated IL-12 in Caco-2 cells, and IL-12 was significantly decreased after AP50 E intervention.Conclusion: The mechanism of the AP50 E on DSS induced ulcerative colitis were preliminary inquiry, results show that, the experimental mice induced by DSS showed clinical symptoms of ulcerative colitis significantly, after drug treatment, the colonic atrophy, hyperemia, edema, acute symptoms were relieved. Further studies showed that, the possible mechanism of AP50 E from grape seeds in the treatment of ulcerative colitis and inhibition of lipid peroxidation in mice, reduce oxidative stress injury; regulate the levels of cytokines, inhibit inflammatory reaction; against excessive apoptosis of intestinal epithelial cells. This experiment for the development and utilization of new drug treatment of ulcerative colitis or health food broaden the thinking and provide the basis, it has great innovation and application value.