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      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

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      Paeoniflorin Alleviates Abnormalities in Rats with Functional Dyspepsia by Stimulating the Release of Acetylcholine

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          Abstract

          Introduction

          Paeoniflorin is a main active component in traditional Chinese medicine. Paeoniae alba radix is widely used as a spasmolytic and pain-relieving agent for abdominal spasmodic pain. Functional dyspepsia (FD) is characterized by pain or burning in the epigastrium, fullness, bloating and nausea. However, limited information is available about the effect of paeoniflorin on FD.

          Materials and Methods

          In this study, iodoacetamide or clonidine-induced FD rat models were established to investigate the impacts of paeoniflorin on FD induced by different pathophysiologic disturbances.

          Results

          We found the therapeutic effect of paeoniflorin through assessing the gastric emptying, gastric accommodation and visceral hypersensitivity. This function of paeoniflorin was related to the release of acetylcholine (ACh), which was accompanied by reduced acetylcholinesterase (AchE) activity in stomach and hypothalamus. Paeoniflorin administration inhibited the cyclo-oxygenase-2 (COX-2) expression and increased the level of ghrelin in the stomach. Besides, the levels of occludin and ZO-1 were elevated in the duodenum from paeoniflorin-treated rats, suggesting the impaired duodenal barrier was ameliorated.

          Discussion

          These results indicate that paeoniflorin possesses the ability to alleviate functional dyspepsia.

          Most cited references48

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          Architecture of tight junctions and principles of molecular composition.

          Menno Van Der Voort, K. Anderson (2014)
          The tight junction creates an intercellular barrier limiting paracellular movement of solutes and material across epithelia. Currently many proteins have been identified as components of the tight junction and understanding their architectural organization and interactions is critical to understanding the biology of the barrier. In general the architecture can be conceptualized into compartments with the transmembrane barrier proteins (claudins, occludin, JAM-A, etc.), linked to peripheral scaffolding proteins (such as ZO-1, afadin, MAGI1, etc.) which are in turned linked to actin and microtubules through numerous linkers (cingulin, myosins, protein 4.1, etc.). Within this complex network are associated many signaling proteins that affect the barrier and broader cell functions. The PDZ domain is a commonly used motif to specifically link individual junction protein pairs. Here we review some of the key proteins defining the tight junction and general themes of their organization with the perspective that much will be learned about function by characterizing the detailed architecture and subcompartments within the junction. Published by Elsevier Ltd.
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            Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia.

            Tim Vanuytsel, Nicolas Pardon, Lukas Oudenhove … (2014)
            Functional dyspepsia (FD) is an extremely common functional gastrointestinal disorder, the pathophysiology of which is poorly understood. We hypothesised that impaired intestinal barrier function is involved in the onset and persistence of this disorder by inducing low-grade inflammation. Therefore, our aim was to evaluate duodenal mucosal integrity and low-grade inflammation in patients with FD. Duodenal biopsy specimens were obtained from 15 patients with FD fulfilling the Rome III criteria and 15 age- and gender-matched healthy volunteers. Transepithelial electrical resistance (TEER) and paracellular permeability were measured in Ussing chambers. Expression of cell-to-cell adhesion proteins was evaluated by real-time PCR, western blot and/or immunofluorescence. Numbers of mast cells, eosinophils and intraepithelial lymphocytes were assessed by immunohistochemistry. Patients with FD displayed lower TEER and increased paracellular passage compared with healthy controls, which is indicative of impaired mucosal integrity. In addition, abnormal expression of cell-to-cell adhesion proteins at the level of tight junctions, adherens junctions and desmosomes was shown. Furthermore, patients were characterised by the presence of low-grade inflammation, as demonstrated by increased infiltration of mucosal mast cells and eosinophils. A significant association between the expression level of several cell-to-cell adhesion proteins, the extent of increased permeability and the severity of low-grade inflammation was found. These findings challenge the classical paradigm that patients with FD show no structural changes in the gastrointestinal tract. We suggest that impaired intestinal barrier function is a pathophysiological mechanism in FD. Thus, restoration of intestinal barrier integrity may be a potential therapeutic target for treating patients with FD.
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              Functional dyspepsia

              Paul Enck, Nicholas J. Talley, Stephan Zipfel … (2017)
              Functional dyspepsia is one of the most prevalent functional gastrointestinal disorders. Functional dyspepsia comprises three subtypes with presumed different pathophysiology and aetiology: postprandial distress syndrome (PDS), epigastric pain syndrome (EPS) and a subtype with overlapping PDS and EPS features. Functional dyspepsia symptoms can be caused by disturbed gastric motility (for example, inadequate fundic accommodation or delayed gastric emptying), gastric sensation (for example, sensations associated with hypersensitivity to gas and bloating) or gastric and duodenal inflammation. A genetic predisposition is probable but less evident than in other functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). Psychiatric comorbidity and psychopathological state and trait characteristics could also play a part, although they are not specific to functional dyspepsia and are less pronounced than in IBS. Possible differential diagnoses include Helicobacter pylori infection and peptic ulceration. Pharmacological therapy is mostly based on the subtype of functional dyspepsia, such as prokinetic and fundus-relaxing drugs for PDS and acid-suppressive drugs for EPS, whereas centrally active neuromodulators and herbal drugs play a minor part. Psychotherapy is effective only in a small subset of patients, whereas quality of life can be severely affected in nearly all patients. Future therapies might include novel compounds that attempt to treat the underlying gastric and duodenal inflammation.
              Article 0 comments Cited 105 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): dddt
                Journal ID (pmc): dddt
                Title: Drug Design, Development and Therapy
                Publisher: Dove
                ISSN (Electronic): 1177-8881
                Publication date (Electronic): 22 December 2020
                Publication date Collection: 2020
                Volume: 14
                Pages: 5623-5632
                Affiliations
                [1 ]Central Laboratory, The First Affiliated Hospital of Dalian Medical University , Dalian 116001, People’s Republic of China
                [2 ]Institute (College) Integrative Medicine, Dalian Medical University , Dalian 116044, People’s Republic of China
                [3 ]Department of Neurology, The First Affiliated Hospital of Dalian Medical University , Dalian 116001, People’s Republic of China
                Author notes
                Correspondence: Zhengxu Cai Department of Neurology, The First Affiliated Hospital of Dalian Medical University , 222 Zhongshan Road, Dalian116001, People’s Republic of China Email caizhengxu999@126.com
                Huishu Guo Central Laboratory, The First Affiliated Hospital of Dalian Medical University , 222 Zhongshan Road, Dalian116001, People’s Republic of ChinaTel +86-411-83635963 ext 7255 Email guohuishu1@126.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-1049-1275
                Article
                Publisher ID: 260703
                DOI: 10.2147/DDDT.S260703
                PMC ID: 7764555
                PubMed ID: 33376306
                SO-VID: 9f8a8c85-2cce-45ee-8281-b8e9c8426de3
                Copyright © © 2020 Zou et al.
                License:

                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
                Date received : 30 April 2020
                Date accepted : 11 November 2020
                Page count
                Figures: 4, References: 48, Pages: 10
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: paeoniflorin,functional dyspepsia,acetylcholine,gastric function
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: paeoniflorin, functional dyspepsia, acetylcholine, gastric function

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