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

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