1-Deoxynojirimycin (DNJ) Ameliorates Indomethacin-Induced Gastric Ulcer in Mice by Affecting NF-kappaB Signaling Pathway

Xuehua Piao; Shuangdi Li; Xiaodan Sui; Lianyi Guo; Xingmei Liu; Hongmei Li; Leming Gao; Shusheng Cai; Yanrong Li; Tingting Wang; Baohai Liu

doi:10.3389/fphar.2018.00372

1-Deoxynojirimycin (DNJ) Ameliorates Indomethacin-Induced Gastric Ulcer in Mice by Affecting NF-kappaB Signaling Pathway

Front Pharmacol. 2018 Apr 19:9:372. doi: 10.3389/fphar.2018.00372. eCollection 2018.

Authors

Xuehua Piao¹, Shuangdi Li², Xiaodan Sui³, Lianyi Guo⁴, Xingmei Liu⁴, Hongmei Li⁴, Leming Gao⁵, Shusheng Cai⁴, Yanrong Li⁴, Tingting Wang⁴, Baohai Liu⁴

Affiliations

¹ Department of Traditional Chinese Medicine, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, China.
² Heart Disease Center, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China.
³ Department of Hepatology, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China.
⁴ Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
⁵ School of Stomatology, 2nd Dental Center, Peking University, Beijing, China.

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 μg DNJ daily), MG (20 μg DNJ daily), HG (40 μg 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-α), 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-α) levels, and key molecules (NF-κB p65), cyclooxygenase 1 (COX-1 and COX2) involved in NF-κB 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-α (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-κB 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-κB signaling pathway, and increases anti-ulceration ability of the models.

Keywords: DNJ; NF-κB signaling pathway; gastric ulceration; mouse; prostaglandin E2.