The Effects Of 3,4-oxo-isopropylidene-shikimic Acid On Ulcerative Colitis In Rats And Its Probable Mechanism

The effects of 3,4-oxo-isopropylidene-shikimic acid on ulcerative colitisin rats and its probable mechanismUlcerative colitis(UC) is a kind of chronic non-specific inflammation mainly related to intestine, Colonic mucous membrane. Its not clear about the etiological factor and pathogenesis until now. it is known that many kinds of immune factors and/or infection factors are involved in this desease, but no specific treatment at present. In clinic, glucocorticoid and 5-amino salicylic acid are common in treating ulcerative colitis, but in view of their serious side-effects, they have been limited to use for long time.3,4-oxo-isopropylidene-shikimic acid( ISA) is a kind of derivative of shikimic acid(SA) which was a component extracted from Illicium verum Hook. fil. The previous research proves that SA has the anti-inflammation and analgesic effect. ISA can inhibit experimental thrombosis and platelet aggregation significantly. In vitro ISA can inhibit human umbilical vein endothelial cell and neutrophil adhesiveness activated by H2O2 and human umbilical vein endothelial cell and leucocyte adhesiveness induced by TNF. Moreover, free radical capture experiment in vitro shows that ISA has the function of elimination of puperoxide anion and OH free radical. Whether ISA has the treatment on UC is not reported yet. In this research, rat colitis model caused by acetic acid and Trinitrobenzenessulfonate(TNBS) were used to observe the treatment of ISA on experimental colitis in rats.Effects of 3,4-oxo-isopropylidene-shikimic acid on ulcerative colitis in rats1 Effects of 3, 4-oxo-isopropylidene-shikimic acid on ulcerative colitis induced by acetic acid in rats and its mechanismTo investigate the effects of 3, 4-oxo-isopropylidene-shikimic acid (ISA) on ulcerative colitis induced by acetic acid in rats.The ulcerative colitis rat model was induced by acetic acid enema. The animals were divided into 6 groups: control group, model group, SASP group (0.50g/kg), ISA groups (0.20, 0.10, 0.05g/kg). The animals were administrated distilled water, SASP and ISA respectively(from the 24h after the establishment of ulcerative colitis model to the end of the experiment, 7d totally). At the end of the experiment, the colon mucosal damage index(CMDI), the activity of myelperoxidase(MPO)and the occult blood test (OB) in feces were observed and mucosa pathohistology was measured. Meanwhile, the content of malondiadehyde(MDA), the vigor of nitric oxide(NO), superoxide dismutase(SOD), glutathione peroxidase(GSH-Px) and nitricoxide synthase(NOS) in colon constitution were detected.After being treated with acetic acid, the body weight in model rats decreased compared with control group. The whole colon length shortened and weight increased due to inflammation, edema and ulceration but the intestine weight index(whole colon weight/length) increased. The extent of OB, CMDI and the level of MPO in model group were higher than them in control group. Colonic mucous membrane pathological change showed the epitheliaabscission and defect. A large amount of neutrophil and lymphocyte infiltrated and ulcer and necrosis formed. Colon mucous membrane disappeared crypt locally or diffusely and mucoprotein excretion decreased or was absent. Edema, hyperemia and bleeding were found around ulcer. Meanwhile the content of MDA> NO and the level of NOS increased in colon of TNBS rats but the level of SOD and GSH-Px decreased. ISA (0.20, 0.10g/kg) ameliorated the extent of CMDI and OB, reduced the level of MPO, MDA, NO and NOS, and increased the activities of SOD and GSH-Px. Pathological histology results showed that colonic mucous membrane epithelia defect relieved and the area for ulcer diminuted significantly, but around ulcer intestinal mucosa covering epithelium proliferated and recovered and some covered. Inflammation cells decreased and granulation tissue hyperplasia remarkedly in ISA group rats. This all showed that treatment with ISA shows beneficial effects on the mucosal damage of rats colitis induced by acetic acid.2 Effects of ISA on...