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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.

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          Most cited references 48

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          Architecture of tight junctions and principles of molecular composition.

          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.

            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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              Systemic review: the prevalence and clinical course of functional dyspepsia.

              To examine the prevalence of functional dyspepsia in the general population, and to evaluate the natural history/clinical course of patients with functional dyspepsia. Full-length published manuscripts during 1980-2002 were included if: (i) participants had uninvestigated or functional dyspepsia; (ii) dyspepsia was defined; (iii) for prevalence, population-based samples were evaluated; (iv) for prognosis, the total number of the inception cohort and the total number of individuals available at the end of follow-up were reported. Twenty-two studies (1976-2002) that examined the prevalence of dyspepsia fulfilled the inclusion and exclusion criteria; 17 studies examined more than 1000 participants, but only two studies provided information sufficient to calculate the prevalence of functional dyspepsia (11.5-14.7%). The prevalence of uninvestigated dyspepsia was in the range 10-40%. When the definition of dyspepsia was restricted to participants with upper abdominal pain, irrespective of the presence of heartburn or acid regurgitation, the prevalence rate estimate was 5-12%. Thirteen studies examined the clinical course of functional dyspepsia (seven retrospective and six prospective). Sample sizes were small (n = 35-209). A follow-up ascertainment of symptoms amongst individuals in the original cohorts was obtained in 92.5-98.2% of prospective studies and in 67.7-82.2% of retrospective studies. The follow-up duration was in the range 1.5-10 years for prospective studies and 5-27 years for retrospective studies; the median follow-up duration for all studies was approximately 5 years. A variable prognosis was reported. An outcome of symptom improvement or becoming asymptomatic was reported in at least one-half of patients in 10 of the 13 studies, and in at least two-thirds of patients in six of the 13 studies. Prognostic factors were inconsistent and, in general, poorly described. Functional dyspepsia is prevalent world-wide, but the prognosis remains poorly defined. There is a need for population-based studies to examine the prevalence and clinical course of documented functional dyspepsia.
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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
                22 December 2020
                2020
                : 14
                : 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

                Article
                260703
                10.2147/DDDT.S260703
                7764555
                © 2020 Zou et al.

                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).

                Page count
                Figures: 4, References: 48, Pages: 10
                Categories
                Original Research

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