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

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.

Preventive Effect of Raw Liubao Tea Polyphenols on Mouse Gastric Injuries Induced by HCl/Ethanol via Anti-Oxidative Stress

“…SP can promote the secretion of gastric acid and pepsin, lead to gastrointestinal contraction, increase the blood flow volume in the stomach, and aggravate gastric injury [ 23 ]. VIP can promote SS release from D cells, can further inhibit the secretion of gastric acid, and plays a positive role in the gastric injury [ 24 ]. When gastric injury happens, VIP level and SS secretion decline, leading to accelerated secretion of gastric acid and high gastric mucosa injury degree [ 25 ].…”

Role of Boswellic Acid in the Treatment of Peptic Ulcer Disease

“…Naito et al (1998) reported that the amounts of malondialdehyde (MDA) and myeloperoxidase (MPO) have increased, as for the levels of glutathione and its enzymes, superoxide dismutase (SOD), catalase (CAT) have decreased in damaged stomach tissue. While for Albayrak et al (2015) and Piao et al (2018) have noted that that the Indomethacin has changed the oxidant-antioxidant balance in stomach tissue, which includes MDA, MPO, GST, SOD, and CAT.…”

Particularities of Experimental Models Used to Induce Gastric Ulcer

“…The fi nancial resources, the end-point of the study, the hypothesis or the research question that has to be tested infl uence the fi nal choice of an experimental model. The preferred animal models used for researches on new agents for the treatment of gastric ulcer are experimental models based on factors influencing the humans' way of life: ulcer induced by ethanol (22) or NSAIDs (23).…”