This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator.
Aim I : To develop a chemically-induced murine-model of ulcerative colitis: Towards this end, we used three groups of 10-week-old female C57BL/6 mice, each group comprising 5 replicates. Experimental groups 1 and 2 were administered 2% and 4% DSS, respectively, via feeding water for 8 days. Control was set up with normal feeding water. Mice body weight and symptoms of disease were monitored every alternate day. Change in body weight was noticeable by D-5, and by D-8, a decrease of 4.7% in group 1 (with 2% DSS) and more than 6% in group 2 (4% DSS) was recorded. Disease symptom such as diarrhea was manifest by 3rd day. While consistency of stool became loose by D-3 in both groups, 4% DSS caused more severity by D-5. Likewise, symptom of rectal bleeding was more severe by D-8 in group 2 with 4% DSS. DSS-treated mice also presented symptoms of pain by huddling. Control registered negligible increase (less than 1%) in body weight with no disease symptoms. DSS mice presented similar disease symptoms in two different sets of experiments when they were used as DSS-control against plumbagin treatments. Size of isolated large intestine was found significantly reduced in DSS mice. In this way, we achieved the first goal.
Aim II : To test the effects of plumbagin on UC pathogenesis in murine model: Four groups of mice (each having 5 replicates) were administered 4% DSS as before. Group 1 and group 2 were treated with plumbagin at the rate of 2mg/kg body weight and 4mg/kg body weight, respectively. Group 3 was treated with plumbagin (2mg/kg) and curcumin (100mg/kg). Drugs were administered via feeding water after 8 days of DSS treatment to all mice. Group 4: DSS-control was given no drug. Plumbagin improved body weight significantly at both doses. Symptoms of diarrhea also improved with plumbagin. Plumbagin was found to be more effective singly than in combination with curcumin, another anti-inflammatory polyphenol. Isolated large intestine was significantly larger than DSS- control. It is hoped that various alterations in the dosage and mode of drug administration will be required to determine the effect clearly.
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