Title | 1-Deoxynojirimycin (DNJ) Ameliorates Indomethacin-Induced Gastric Ulcer in Mice by Affecting NF-kappaB Signaling Pathway |
Authors | Piao, Xuehua Li, Shuangdi Sui, Xiaodan Guo, Lianyi Liu, Xingmei Li, Hongmei Gao, Leming Cai, Shusheng Li, Yanrong Wang, Tingting Liu, Baohai |
Affiliation | Jinzhou Med Univ, Affiliated Hosp 1, Dept Tradit Chinese Med, Jinzhou, Peoples R China. Changchun Univ Tradit Chinese Med, Heart Dis Ctr, Affiliated Hosp, Changchun, Jilin, Peoples R China. Changchun Univ Tradit Chinese Med, Dept Hepatol, Affiliated Hosp, Changchun, Jilin, Peoples R China. Jinzhou Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Jinzhou, Peoples R China. Peking Univ, Sch Stomatol, Dent Ctr 2, Beijing, Peoples R China. |
Keywords | NF-kappa B signaling pathway mouse gastric ulceration DNJ prostaglandin E2 ALPHA-GLUCOSIDASE OXIDATIVE STRESS PROSTAGLANDIN E-2 BACILLUS-SUBTILIS MULBERRY LEAVES MARGINAL ULCER DIABETIC-RATS BLOOD-GLUCOSE NITRIC-OXIDE ALOE-VERA |
Issue Date | 2018 |
Publisher | FRONTIERS IN PHARMACOLOGY |
Citation | FRONTIERS IN PHARMACOLOGY. 2018, 9. |
Abstract | Gastric ulcer (GU) is a main threat to public health. 1-Deoxynojirimycin (DNJ) has antioxidant and anti-inflammatory properties and may prevent GU but related mechanism remains unclear. DNJ was extracted from the supernatants of Bacillus subtilis by using ethanol and purified by using CM-Sepharose chromatography. A GU mouse model was induced by indomethacin. The functional role of DNJ in GU mice was explored by measuring the main molecules in the NF-KappaB pathway. After the model establishment, 40 GU mice were evenly assigned into five categories: IG (received vehicle control), LG (10 mu g DNJ daily), MG (20 mu g DNJ daily), HG (40 mu g DNJ daily), and RG (0.5 mg ranitidine daily). Meanwhile, eight healthy mice were assigned as a control group (CG). After 1-month therapy, weight and gastric volume were investigated. The levels of serum inflammatory cytokines (IL-6 and TNF-alpha), antioxidant indices [superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)], and oxidant biomarker malondialdehyde (MDA) were examined via ELISA. Meanwhile, inflammatory cytokine (IL-6 and TNF-alpha) levels, and key molecules (NF-kappa B p65), cyclooxygenase 1 (COX-1 and COX2) involved in NF-kappa B pathway, were analyzed by using Western Blot. COX-1 and COX-2 levels were further measured by immunohistochemistry. The effects of DNJ on gastric functions were explored by measuring the changes of Motilin (MOT), Substance P (SP), Somatostatin (SS), and Vasoactive intestinal peptide (VIP) in GU mouse models with ELISA Kits. The results indicated that DNJ prevented indomethacin-caused increase of gastric volume. DNJ improved histopathology of GU mice when compared with the mice from IG group (P < 0.05). DNJ consumption decreased the levels of IL-6 and TNF-a (P < 0.05). DNJ increased antioxidant indices of GU mice by improving the activities of SOD, CAT and reduced GSH, and reduced MDA levels (P < 0.05). DNJ increased the levels of prostaglandin E2, COX-1, COX2, and reduced the levels of and NF-kappa B p65 (P < 0.05). DNJ showed protection for gastric functions of GU mice by reducing the levels of MOT and SP, and increasing the levels of SS and VIP. DNJ treatment inactivates NF-kappa B signaling pathway, and increases anti-ulceration ability of the models. |
URI | http://hdl.handle.net/20.500.11897/524275 |
ISSN | 1663-9812 |
DOI | 10.3389/fphar.2018.00372 |
Indexed | SCI(E) PubMed |
Appears in Collections: | 口腔医院 |