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      Cyanidin-3-O-Glucoside Improves Colonic Motility During Severe Acute Pancreatitis by Inhibiting the H 2S-Regulated AMPK/mTOR Pathway

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          Abstract

          Background

          Cyanidin-3-O-glucoside (C3G) is an important anthocyanin that can modulate digestive system functioning. Inflammation associated with severe acute pancreatitis (SAP) induces H 2S production, which impairs the gastrointestinal (GI) system. We investigated the effects of C3G in attenuating SAP-associated colonic motility loss by examining the H 2S level and activity of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway.

          Methods

          A rat model of SAP was induced using sodium taurocholate, and the effect of C3G on colonic mobility, H 2S production, and the inflammatory response was investigated. AMPK/mTOR pathway changes were detected to assess the pathways by which H 2S influences colonic mobility in SAP-model rats. The mechanism underlying H 2S function was further examined by subjecting colonic muscle cells (CMCs) to C3G, SAP plasma and an AMPK activator.

          Results

          Administering C3G improved colonic motility but suppressed the inflammatory response and H 2S production in the SAP-model rats, which was associated with inhibiting the AMPK/mTOR pathway. Furthermore, activating the AMPK/mTOR pathway in CMCs promoted inflammation but suppressed Ca2+ levels, even after administering C3G.

          Conclusion

          Administering C3G may improve SAP-associated colonic mobility by inhibiting the H 2S-mediated AMPK/mTOR pathway.

          Most cited references31

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          2019 WSES guidelines for the management of severe acute pancreatitis

          Although most patients with acute pancreatitis have the mild form of the disease, about 20–30% develops a severe form, often associated with single or multiple organ dysfunction requiring intensive care. Identifying the severe form early is one of the major challenges in managing severe acute pancreatitis. Infection of the pancreatic and peripancreatic necrosis occurs in about 20–40% of patients with severe acute pancreatitis, and is associated with worsening organ dysfunctions. While most patients with sterile necrosis can be managed nonoperatively, patients with infected necrosis usually require an intervention that can be percutaneous, endoscopic, or open surgical. These guidelines present evidence-based international consensus statements on the management of severe acute pancreatitis from collaboration of a panel of experts meeting during the World Congress of Emergency Surgery in June 27–30, 2018 in Bertinoro, Italy. The main topics of these guidelines fall under the following topics: Diagnosis, Antibiotic treatment, Management in the Intensive Care Unit, Surgical and operative management, and Open abdomen.
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            Hydrogen sulfide and inflammation: the good, the bad, the ugly and the promising.

            Hydrogen sulfide is rapidly gaining ground as a physiological mediator of inflammation, but there is no clear consensus as to its precise role in inflammatory signaling. This article discusses the disparate anti-inflammatory ('the good') and proinflammatory ('the bad') effects of endogenous and pharmacological H(2)S in disparate animal model and cell culture systems. We also discuss 'the ugly', such as problems of using wholly specific inhibitors of enzymatic H(2)S synthesis, and the use of pharmacological donor compounds, which release H(2)S too quickly to be physiologically representative of endogenous H(2)S synthesis. Furthermore, recently developed slow-release H(2)S donors, which offer a more physiological approach to understanding the complex role of H(2)S in acute and chronic inflammation ('the promising') are discussed.
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              Severe acute pancreatitis: pathogenesis, diagnosis and surgical management

              Severe acute pancreatitis is a subtype of acute pancreatitis, associated with multiple organ failure and systemic inflammatory response syndrome. In this qualitative review we looked at the principles of pathogenesis, classification and surgical management of severe acute pancreatitis. We also looked at the current shift in paradigm in the management of severe acute pancreatitis since the guideline developed by the British Society of Gastroenterology.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                19 August 2020
                2020
                : 14
                : 3385-3391
                Affiliations
                [1 ]Department of Gastroenterology, Southwest Hospital of Army Medical University , Chongqing, People’s Republic of China
                Author notes
                Correspondence: Wensheng Chen Department of Gastroenterology, Southwest Hospital of Army Medical University , Gaotanyanzheng Street, Shapingba District, Chongqing400038, People’s Republic of China Email wensheng_c1241@126.com
                Author information
                https://orcid.org/http://orcid.org/0000-0001-6683-8744
                Article
                256450
                10.2147/DDDT.S256450
                7468407
                dab57a8e-5248-4e0a-9124-0fdaaf2bf231
                © 2020 Lian and Chen.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 01 April 2020
                : 22 July 2020
                Page count
                Figures: 4, References: 33, Pages: 7
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                amp-activated protein kinase,ampk,cyanidin-3-o-glucoside,colonic motility,severe acute pancreatitis,hydrogen sulfide

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