S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Ph.D. / Sc.D._의학과)
Nimbolide Inhibits Nuclear Factor-κB Pathway in Intestinal Epithelial Cells and Macrophages, and Alleviates Experimental Colitis in Mice
Nimbolide의 Nuclear Factor-κB 신호 전달 억제 및 대장염 마우스 모델 염증 완화 효과
- 김주성 교수님
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2017. 2. 김주성.
- Introduction: Nimbolide is a limonoid extracted from neem tree (Azadirachta indica) that has antiinflammatory properties. The aim of this study was to investigate the effect of nimbolide on the nuclear factor-kappa B (NF-κB) pathway in intestinal epithelial cells (IECs), macrophages and in murine colitis models.
Methods: The IEC cell-line COLO 205, the murine macrophage cell-line RAW 264.7 and peritoneal macrophages extracted from interleukin (IL)-10 deficient (IL-10-/-) mice were preconditioned with nimbolide or vehicle and then stimulated. The secretion of inflammatory cytokines (IL-6, IL-8, IL-12 and tumor necrosis factor-α) was examined by ELISA. Effects on the NF-κB pathway were evaluated by western blot of IκBα phosphorylation and electrophoretic mobility shift assay. Dextran sulfate sodium (DSS)-induced acute colitis model and chronic colitis model in IL-10-/- mice were used for in vivo experiments. Colitis was estimated by disease activity index (DAI) and histopathologic evaluation.
Results: Nimbolide significantly suppressed the expression of inflammatory cytokines, and inhibited the phosphorylation of IκBα and the DNA-binding affinity of NF-κB in IECs and macrophages. Nimbolide was effective in both DSS-induced acute colitis and in IL-10-/- chronic colitis: It ameliorated weight loss, colon shortening, DAI score and histologic scores in DSS colitis. It also improved histopathologic scores in the chronic colitis of IL-10-/- mice. Staining for phosphorylated IκBα was significantly decreased in colon tissue after treatment with nimbolide in both models.
Conclusions: Nimbolide inhibits NF-κB signaling in IECs and macrophages, and ameliorates experimental colitis in mice. Our results suggest nimbolide could be a potentially new treatment for inflammatory bowel disease.