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      Protective effects of total flavonoids from Alpinia officinarum rhizoma against ethanol-induced gastric ulcer in vivo and in vitro

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          Abstract

          Context

          Alpinia officinarum Hance (Zingiberaceae) is traditionally used to treat inflammation, pain, colds and digestive diseases.

          Objective

          To investigate the potential protective mechanism of total flavonoids from the rhizomes of A. officinarum (F-AOH) in ethanol-induced acute gastric in vivo and in vitro.

          Materials and methods

          In vivo: Gastric damage was induced in BALB/c mice by administering ethanol (10 mL/kg) after oral treatment with F-AOH at 126.8, 63.4 and 31.7 mg/kg or ranitidine (Ran) at 100 mg/kg (1 week of continuous gavage). In vitro: Gastric mucosal epithelial cells (GES-1) were incubated with F-AOH (8, 4 and 2 μg/mL) for 16 h and treated with 7% ethanol for 4 h. The extent of gastric damage was assessed histopathologically, and the expression of NF-κB, COX-2, TNF-α, iNOS and IL-1β was quantified by Western blot analysis. In addition, proinflammatory mediators and concentrations of motilin (MTL) and gastrin (GAS) were measured by ELISA test.

          Results

          F-AOH effectively reduced the ulcer index (from 23.4 ± 4.28 to 8.32 ± 1.5) and reduced release of inflammatory mediators (IL-1β, IL-6, TNF-α and PGE2), increased the content of nitric oxide and improved GAS and MTL secretion. The 50% inhibitory concentration (IC 50) of F-AOH on cell damage was 17 μg/mL. F-AOH increased ethanol-induced cell survival (from 47 to 85%) and inhibited the expression of NF-κB, COX-2, TNF-α, IL-1β and iNOS proteins.

          Conclusions

          F-AOH inhibits ethanol-induced gastric mucosal damage, provides a theoretical basis for galangal in the treatment of other causes of GU, and promotes the application of galanga in the treatment of GU.

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          Most cited references38

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          Neutrophil infiltration favors colitis-associated tumorigenesis by activating the interleukin-1 (IL-1)/IL-6 axis.

          Neutrophil infiltration is a key event in chronic intestinal inflammation and associated colorectal cancer, but how these cells support cancer development is poorly understood. In this study, using a mouse model of colitis-associated cancer (CAC), we have demonstrated that infiltrated neutrophils produce large amounts of interleukin-1 (IL)-1β that is critical for the development of CAC. Depletion of neutrophil or blockade of IL-1β activity significantly reduced mucosal damage and tumor formation. This protumorigenic function of IL-1β was mainly attributed to increased IL-6 secretion by intestine-resident mononuclear phagocytes (MPs). Furthermore, commensal flora-derived lipopolysaccharide (LPS) was identified to trigger IL-1β expression in neutrophils. Importantly, accumulation of IL-1β-expressing neutrophils was seen in lesions of patients suffering from ulceratic CAC and these infiltrated neutrophils induced IL-6 production by intestinal MPs in an IL-1β-dependent manner. Overall, these findings reveal that in CAC milieu, infiltrating neutrophils secrete IL-1β that promotes tumorigenesis by inducing IL-6 production by intestinal MPs.
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            The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine

            Non-steroidal anti-inflammatory drugs are the most commonly prescribed drugs for arthritis, inflammation, and cardiovascular protection. However, they cause gastrointestinal complications. The pathophysiology of these complications has mostly been ascribed to non-steroidal anti-inflammatory drugs’ action on the cyclooxygenase inhibition and the subsequent prostaglandin deficiency. However, recent clinical demonstrated the prevalence of non-steroidal anti-inflammatory drugs-induced small intestinal mucosal injury is more often than previously expected. In this review, we discuss the defense mechanisms of stomach, and the pathophysiology of non-steroidal anti-inflammatory drugs-induced injury of stomach and small intestine, especially focused on non-steroidal anti-inflammatory drugs’ action on mitochondria.
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              The Gastroprotective Effect of Menthol: Involvement of Anti-Apoptotic, Antioxidant and Anti-Inflammatory Activities

              The aim of this research was to investigate the anti-apoptotic, antioxidant and anti-inflammatory properties of menthol against ethanol-induced gastric ulcers in rats. Wistar rats were orally treated with vehicle, carbenoxolone (100 mg/kg) or menthol (50 mg/kg) and then treated with ethanol to induce gastric ulcers. After euthanasia, stomach samples were prepared for histological slides and biochemical analyses. Immunohistochemical analyses of the cytoprotective and anti-apoptotic heat-shock protein-70 (HSP-70) and the apoptotic Bax protein were performed. The neutrophils were manually counted. The activity of the myeloperoxidase (MPO) was measured. To determine the level of antioxidant functions, the levels of glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD) were measured using ELISA. The levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the anti-inflammatory cytokine interleukin-10 (IL-10) were assessed using ELISA kits. The menthol treated group presented 92% gastroprotection compared to the vehicle-treated group. An increased immunolabeled area was observed for HSP-70, and a decreased immunolabeled area was observed for the Bax protein in the menthol treated group. Menthol treatment induced a decrease in the activity of MPO and SOD, and the protein levels of GSH, GSH-Px and GR were increased. There was also a decrease in the levels of TNF-α and IL-6 and an increase in the level of IL-10. In conclusion, oral treatment with menthol displayed a gastroprotective activity through anti-apoptotic, antixidant and anti-inflammatory mechanisms.
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                Author and article information

                Journal
                Pharm Biol
                Pharm Biol
                Pharmaceutical Biology
                Taylor & Francis
                1388-0209
                1744-5116
                1 September 2020
                2020
                1 September 2020
                : 58
                : 1
                : 854-862
                Affiliations
                [a ]Key Laboratory of Tropical Translational Medicine of Ministry of Education , Haikou, China
                [b ]Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs , Haikou, China
                [c ]School of Pharmacy, Hainan Medical University , Haikou, China
                [d ]Intervention Vascular Surgery of First Affiliated Hospital of Hainan Medical University , Haikou, China
                [e ]Ministry of Education, Key Laboratory of Emergency and Trauma of Hainan Medical University , Haikou, China
                Author notes
                CONTACT Na Wei weina-0613@ 123456163.com Hainan Medical University , 3 Xueyuan Road, Haikou 571199, China
                Author information
                https://orcid.org/0000-0002-8622-3920
                Article
                1803370
                10.1080/13880209.2020.1803370
                8641678
                32871094
                b326490f-dee3-4bf9-9254-f349d3ac04e3
                © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 7, Tables: 0, Pages: 9, Words: 6041
                Categories
                Research Article
                Research Article

                gastroprotection,inflammatory cytokines,gastric cytoprotection,nitric oxide,nf-κb,cox-2,flavonoids

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