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Layer P, Andresen V, Allescher H, Bischoff SC, Claßen M, Elsenbruch S, Freitag M, Frieling T, Gebhard M, Goebel-Stengel M, Häuser W, Holtmann G, Keller J, Kreis ME, Kruis W, Langhorst J, Jansen PL, Madisch A, Mönnikes H, Müller-Lissner S, Niesler B, Pehl C, Pohl D, Raithel M, Röhrig-Herzog G, Schemann M, Schmiedel S, Schwille-Kiuntke J, Storr M, Preiß JC, Andus T, Buderus S, Ehlert U, Engel M, Enninger A, Fischbach W, Gillessen A, Gschossmann J, Gundling F, Haag S, Helwig U, Hollerbach S, Karaus M, Katschinski M, Krammer H, Kuhlbusch-Zicklam R, Matthes H, Menge D, Miehlke S, Posovszky MC, Schaefert R, Schmidt-Choudhury A, Schwandner O, Schweinlin A, Seidl H, Stengel A, Tesarz J, van der Voort I, Voderholzer W, von Boyen G, von Schönfeld J, Wedel T. Update S3-Leitlinie Reizdarmsyndrom: Definition, Pathophysiologie, Diagnostik und Therapie. Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM) – Juni 2021 – AWMF-Registriernummer: 021/016. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:1323-1415. [PMID: 34891206 DOI: 10.1055/a-1591-4794] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- P Layer
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - V Andresen
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - H Allescher
- Zentrum für Innere Medizin, Gastroent., Hepatologie u. Stoffwechsel, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Deutschland
| | - S C Bischoff
- Institut für Ernährungsmedizin, Universität Hohenheim, Stuttgart, Deutschland
| | - M Claßen
- Klinik für Kinder- und Jugendmedizin, Klinikum Links der Weser, Bremen, Deutschland
| | - S Elsenbruch
- Klinik für Neurologie, Translational Pain Research Unit, Universitätsklinikum Essen, Essen, Deutschland.,Abteilung für Medizinische Psychologie und Medizinische Soziologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - M Freitag
- Abteilung Allgemeinmedizin Department für Versorgungsforschung, Universität Oldenburg, Oldenburg, Deutschland
| | - T Frieling
- Medizinische Klinik II, Helios Klinikum Krefeld, Krefeld, Deutschland
| | - M Gebhard
- Gemeinschaftspraxis Pathologie-Hamburg, Hamburg, Deutschland
| | - M Goebel-Stengel
- Innere Medizin II, Helios Klinik Rottweil, Rottweil, und Innere Medizin VI, Psychosomat. Medizin u. Psychotherapie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - W Häuser
- Innere Medizin I mit Schwerpunkt Gastroenterologie, Klinikum Saarbrücken, Saarbrücken, Deutschland
| | - G Holtmann
- Faculty of Medicine & Faculty of Health & Behavioural Sciences, Princess Alexandra Hospital, Brisbane, Australien
| | - J Keller
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - M E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
| | | | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg, Deutschland
| | - P Lynen Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten, Berlin, Deutschland
| | - A Madisch
- Klinik für Gastroenterologie, interventionelle Endoskopie und Diabetologie, Klinikum Siloah, Klinikum Region Hannover, Hannover, Deutschland
| | - H Mönnikes
- Klinik für Innere Medizin, Martin-Luther-Krankenhaus, Berlin, Deutschland
| | | | - B Niesler
- Abteilung Molekulare Humangenetik Institut für Humangenetik, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - C Pehl
- Medizinische Klinik, Krankenhaus Vilsbiburg, Vilsbiburg, Deutschland
| | - D Pohl
- Klinik für Gastroenterologie und Hepatologie, Universitätsspital Zürich, Zürich, Schweiz
| | - M Raithel
- Medizinische Klinik II m.S. Gastroenterologie und Onkologie, Waldkrankenhaus St. Marien, Erlangen, Deutschland
| | | | - M Schemann
- Lehrstuhl für Humanbiologie, TU München, Deutschland
| | - S Schmiedel
- I. Medizinische Klinik und Poliklinik Gastroenterologie, Universitätsklinikum Hamburg-Eppendorf, Deutschland
| | - J Schwille-Kiuntke
- Abteilung für Psychosomatische Medizin und Psychotherapie, Medizinische Universitätsklinik Tübingen, Tübingen, Deutschland.,Institut für Arbeitsmedizin, Sozialmedizin und Versorgungsforschung, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - M Storr
- Zentrum für Endoskopie, Gesundheitszentrum Starnberger See, Starnberg, Deutschland
| | - J C Preiß
- Klinik für Innere Medizin - Gastroenterologie, Diabetologie und Hepatologie, Vivantes Klinikum Neukölln, Berlin, Deutschland
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Lu Y, Huang J, Zhang Y, Huang Z, Yan W, Zhou T, Wang Z, Liao L, Cao H, Tan B. Therapeutic Effects of Berberine Hydrochloride on Stress-Induced Diarrhea-Predominant Irritable Bowel Syndrome Rats by Inhibiting Neurotransmission in Colonic Smooth Muscle. Front Pharmacol 2021; 12:596686. [PMID: 34594213 PMCID: PMC8476869 DOI: 10.3389/fphar.2021.596686] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 09/01/2021] [Indexed: 11/13/2022] Open
Abstract
The etiology of diarrhea-predominant irritable bowel syndrome (IBS-D) is complicated and closely related to neurotransmission in the gastrointestinal (GI) tract. Developing new strategies for treating this disease is a major challenge for IBS-D research. Berberine hydrochloride (BBH), the derivative of berberine, is a herbal constituent used to treat IBS. Previous studies have shown that BBH has potential anti-inflammatory, antibacterial, analgesic, and antidiarrheal effects and a wide range of biological activities, especially in regulating the release of some neurotransmitters. A modified IBS-D rat model induced by chronic restraint stress was used in all experiments to study the effects of BBH on the GI tract. This study measured the abdominal withdrawal reflex (AWR) response to graded colorectal distention (CRD; 20, 40, 60, and 80 mmHg) and observed the fecal areas of stress-induced IBS-D model. Experiments were conducted using organ bath techniques, which were performed in vitro using strips of colonic longitudinal smooth muscle. Inhibitory and excitatory neurotransmitter agents were added to each organ bath to observe contractile responses on the strips and the treatment effect exerted by BBH. The IBS-D rat model was successfully induced by chronic restraint stress, which resulted in an increased defecation frequency and visceral hypersensitivity similar to that of humans. BBH could reduce 4-h fecal areas and AWR response to CRD in IBS-D. The stress-induced IBS-D model showed upregulated colonic mRNA expression levels of 5-hydroxytryptamine-3A receptor and downregulated expression levels of neuronal nitric oxide synthase. Meanwhile, BBH could reverse this outcome. The responses of substances that regulate the contraction induced by related neurotransmission in the longitudinal smooth muscle of IBS-D colon (including the agonist of acetylcholine, carbachol; NOS inhibitor, L-NAME; and P2Y1 receptor antagonist, MRS2500) can be inhibited by BBH. In summary, BBH promotes defecation frequency and visceral hypersensitivity in IBS-D and exerts inhibitory effects on contractile responses in colonic longitudinal smooth muscle. Thus, BBH may represent a new therapeutic approach for treating IBS-D.
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Affiliation(s)
- Yulin Lu
- Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jingjing Huang
- Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yao Zhang
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zitong Huang
- Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Weiming Yan
- The Third Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Tianran Zhou
- The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Zhesheng Wang
- Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Lu Liao
- Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hongying Cao
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Bo Tan
- Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
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Altomare A, Gori M, Cocca S, Carotti S, Francesconi M, Ribolsi M, Emerenziani S, Perrone G, Morini S, Cicala M, Guarino MPL. Impaired Colonic Contractility and Intestinal Permeability in Symptomatic Uncomplicated Diverticular Disease. J Neurogastroenterol Motil 2021; 27:292-301. [PMID: 33594008 PMCID: PMC8026365 DOI: 10.5056/jnm20110] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 10/31/2020] [Accepted: 12/08/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND/AIMS Impaired intestinal motility seems to play a crucial role in symptomatic uncomplicated diverticular disease (SUDD), although the mechanism is not clear. The aim of the present study is to explore the contractility patterns of colonic smooth muscle strips (MS) and smooth muscle cells (SMCs) and to assess mucosal integrity in SUDD patients. METHODS MS or SMCs were isolated from specimens of human distal colon of 18 patients undergoing surgery for non-obstructive colonic cancer, among them 9 with SUDD. Spontaneous phasic contractions on strips and morpho-functional parameters on cells were evaluated in basal conditions and in response to acetylcholine (ACh). Mucosal integrity of SUDD colonic biopsies was evaluated by the Ussing Chamber system. Immunohistochemical staining for tight junction protein complex and for Toll-like receptor 4 (TLR4) was performed. RESULTS Colonic MS of SUDD group showed a significant reduced basal tone and ACh-elicited contraction, compared to the control group (9.5 g and 47.0% in the SUDD group; 14.16 g and 69.0% in the control group; P < 0.05). SMCs of SUDD group showed a maximal contractile response to ACh significantly reduced compared to control group (8.8% vs 16.5%, P < 0.05). SUDD patients displayed lower transepithelial electrical resistance and increased paracellular permeability compared to control group. Immunohistochemical expression of TLR4 was not different in both groups, while tight junction protein complex expression was lower in SUDD patients compared to control group patients. CONCLUSION It could be hypothesized that in SUDD, in absence of severe inflammation, an increased intestinal mucosal permeability is related to altered colonic motility probably responsible for symptoms genesis.
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Affiliation(s)
- Annamaria Altomare
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Manuele Gori
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
- Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Monterotondo Scalo, Rome, Italy
| | - Silvia Cocca
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Simone Carotti
- Microscopic and Ultrastructural Anatomy Unit, Università Campus Bio-Medico di Roma, Rome, Italy
- Predictive Molecular Diagnostic Division, Department of Pathology, Campus Bio-Medico University Hospital, Rome, Italy
| | - Maria Francesconi
- Microscopic and Ultrastructural Anatomy Unit, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Mentore Ribolsi
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Sara Emerenziani
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Giuseppe Perrone
- Predictive Molecular Diagnostic Division, Department of Pathology, Campus Bio-Medico University Hospital, Rome, Italy
| | - Sergio Morini
- Microscopic and Ultrastructural Anatomy Unit, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Michele Cicala
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Michele P L Guarino
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
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Vona R, Pallotta L, Cappelletti M, Severi C, Matarrese P. The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders. Antioxidants (Basel) 2021; 10:201. [PMID: 33573222 PMCID: PMC7910878 DOI: 10.3390/antiox10020201] [Citation(s) in RCA: 165] [Impact Index Per Article: 41.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 01/22/2021] [Accepted: 01/26/2021] [Indexed: 12/15/2022] Open
Abstract
Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of many diseases. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant systems has been extensively studied in pulmonary, neurodegenerative cardiovascular disorders; however, its contribution is still debated in gastrointestinal disorders. Evidence suggests that oxidative stress affects gastrointestinal motility in obesity, and post-infectious disorders by favoring the smooth muscle phenotypic switch toward a synthetic phenotype. The aim of this review is to gain insight into the role played by oxidative stress in gastrointestinal pathologies (GIT), and the involvement of ROS in the signaling underlying the muscular alterations of the gastrointestinal tract (GIT). In addition, potential therapeutic strategies based on the use of antioxidants for the treatment of inflammatory gastrointestinal diseases are reviewed and discussed. Although substantial progress has been made in identifying new techniques capable of assessing the presence of oxidative stress in humans, the biochemical-molecular mechanisms underlying GIT mucosal disorders are not yet well defined. Therefore, further studies are needed to clarify the mechanisms through which oxidative stress-related signaling can contribute to the alteration of the GIT mucosa in order to devise effective preventive and curative therapeutic strategies.
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Affiliation(s)
- Rosa Vona
- Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy;
| | - Lucia Pallotta
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy; (L.P.); (M.C.); (C.S.)
| | - Martina Cappelletti
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy; (L.P.); (M.C.); (C.S.)
| | - Carola Severi
- Department of Translational and Precision Medicine, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy; (L.P.); (M.C.); (C.S.)
| | - Paola Matarrese
- Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy;
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Nyavor Y, Brands CR, Nicholson J, Kuther S, Cox KK, May G, Miller C, Yasuda A, Potter F, Cady J, Heyman HM, Metz TO, Stark TD, Hofmann T, Balemba OB. Supernatants of intestinal luminal contents from mice fed high-fat diet impair intestinal motility by injuring enteric neurons and smooth muscle cells. Neurogastroenterol Motil 2021; 33:e13990. [PMID: 32969549 DOI: 10.1111/nmo.13990] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 08/12/2020] [Accepted: 08/25/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Damage to enteric neurons and impaired gastrointestinal muscle contractions cause motility disorders in 70% of diabetic patients. It is thought that enteric neuropathy and dysmotility occur before overt diabetes, but triggers of these abnormalities are not fully known. We tested the hypothesis that intestinal contents of mice with and without high-fat diet- (HFD-) induced diabetic conditions contain molecules that impair gastrointestinal movements by damaging neurons and disrupting muscle contractions. METHODS Small and large intestinal segments were collected from healthy, standard chow diet (SCD) fed mice. Filtrates of ileocecal contents (ileocecal supernatants; ICS) from HFD or SCD mice were perfused through them. Cultured intact intestinal muscularis externa preparations were used to determine whether ICS and their fractions obtained by solid-phase extraction (SPE) and SPE subfractions collected by high-performance liquid chromatography (HPLC) disrupt muscle contractions by injuring neurons and smooth muscle cells. KEY RESULTS ICS from HFD mice reduced intestinal motility, but those from SCD mice had no effect. ICS, aqueous SPE fractions and two out of twenty HPLC subfractions of aqueous SPE fractions from HFD mice blocked muscle contractions, caused a loss of nitrergic myenteric neurons through inflammation, and reduced smooth muscle excitability. Lipopolysaccharide and palmitate caused a loss of nitrergic myenteric neurons but did not affect muscle contractions. CONCLUSIONS & INFERENCES Unknown molecules in intestinal contents of HFD mice trigger enteric neuropathy and dysmotility. Further studies are required to identify the toxic molecules and their mechanisms of action.
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Affiliation(s)
- Yvonne Nyavor
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | | | - Jessica Nicholson
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Sydney Kuther
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Kortni K Cox
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - George May
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | | | - Allysha Yasuda
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Forrest Potter
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Joshua Cady
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Heino M Heyman
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Thomas O Metz
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Timo D Stark
- Lehrstuhl für Lebensmittelchemie und Molekulare Sensorik, Technische Universität München, Freising, Germany
| | - Thomas Hofmann
- Lehrstuhl für Lebensmittelchemie und Molekulare Sensorik, Technische Universität München, Freising, Germany
| | - Onesmo B Balemba
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
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Wang Y, Dong Y, Wang E, Meng Y, Bi Z, Sun S, Zhang C, Fan H, Yuan J. Shugan Decoction Alleviates Colonic Dysmotility in Female SERT-Knockout Rats by Decreasing M 3 Receptor Expression. Front Pharmacol 2020; 11:01082. [PMID: 33013355 PMCID: PMC7516163 DOI: 10.3389/fphar.2020.01082] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Accepted: 07/02/2020] [Indexed: 12/12/2022] Open
Abstract
Background Irritable bowel syndrome (IBS) is a functional gut disease characterized by visceral hypersensitivity and gut motor dysfunction. Serotonin (5-hydroxytryptamine, 5-HT) is an important enteric neurotransmitter. High levels of 5-HT aggravate IBS symptoms. The serotonin reuptake transporter (SERT) is a membrane-embedded transporter involved in IBS pathogenesis that plays an important role in regulating 5-HT signaling. Aim We investigated whether gut motor function was altered in SERT-knockout (SERT-KO) rats. Additionally, we sought to determine whether Shugan decoction (SGD), a clinically experienced prescription for the treatment of IBS, exerts regulatory effects on intestinal motility in SERT-KO rats, and attempted to identify the mechanisms involved. Method SERT-KO rats were produced by transcription activator-like effector nuclease (TALEN) technology. Fecal pellet output was measured for ten consecutive days to estimate distal colonic motility. Small intestinal motility was measured by charcoal-meal experiments. The colonic and small intestinal muscle contractile activities were measured by organ bath study. Western blot was used to analyze the muscarinic receptor expression in colon tissue. Result Compared with that in wild-type (WT) rats, the defecation amount, amplitude of spontaneous contraction, and the tension of ACh-induced contraction of colonic longitudinal smooth muscle in SERT-KO rats were significantly increased. The expression of muscarinic receptor subtype-3 (M3R) in the colons of SERT-KO rats was also elevated. SGD can decrease defecation of SERT-KO rats. Moreover, SGD reduced the amplitude of spontaneous contraction, the frequency and tension of ACh-induced contraction of colonic longitudinal smooth muscle, and the expression of M3R in the colon in SERT-KO rats. Conclusions SERT-KO rats showed increased defecation accompanied by enhanced colonic motility and M3R expression. The findings suggest that SGD modifies colonic dysmotility and reduces defecation in SERT-KO rats by down-regulating M3R expression in the colon.
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Affiliation(s)
- Yinshu Wang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ying Dong
- School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Enkang Wang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yangyang Meng
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zijuan Bi
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Shuai Sun
- Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Chaochao Zhang
- Laboratory Animal Center, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Haiting Fan
- Laboratory Animal Center, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jianye Yuan
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Zhou TR, Huang JJ, Huang ZT, Cao HY, Tan B. Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome. World J Gastroenterol 2018; 24:693-705. [PMID: 29456408 PMCID: PMC5807672 DOI: 10.3748/wjg.v24.i6.693] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 11/06/2017] [Accepted: 11/28/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To elucidate the mechanism of patchouli alcohol (PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS We studied the effects of PA on colonic spontaneous motility using its cumulative log concentration (3 × 10-7 mol/L to 1 × 10-4 mol/L). We then determined the responses of the proximal and distal colon segments of rats to the following stimuli: (1) carbachol (1 × 10-9 mol/L to 1 × 10-5 mol/L); (2) neurotransmitter antagonists including Nω-nitro-L-arginine methyl ester hydrochloride (10 μmol/L) and (1R*, 2S*)-4-[2-Iodo-6-(methylamino)-9H-purin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt (1 μmol/L); (3) agonist α,β-methyleneadenosine 5'-triphosphate trisodium salt (100 μmol/L); and (4) single KCl doses (120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA (100 μmol/L) for 1 min. Electrical-field stimulation (40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of Kreb's solution was also determined. RESULTS PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration (EC50) was 41.9 μmol/L. In comparison with the KCl-treated IBS-D group, the contractile response (mg contractions) in the PA + KCl-treated IBS-D group (11.87 ± 3.34) was significantly decreased in the peak tension (P < 0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle (EC50 = 0.94 μmol/L) was significantly decreased by PA (EC50 = 37.43 μmol/L) (P < 0.05). Lack of nitrergic neurotransmitter release in stress-induced IBS-D rats showed contraction effects on colonic smooth muscle. Pretreatment with PA resulted in inhibitory effect on L-NAME-induced (10 μmol/L) contraction (P < 0.05). ATP might not be the main neurotransmitter involved in inhibitory effects of PA in the colonic relaxation of stress-induced IBS-D rats. CONCLUSION PA application may serve as a new therapeutic approach for IBS-D.
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Affiliation(s)
- Tian-Ran Zhou
- The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Jing-Jing Huang
- The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Zi-Tong Huang
- The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Hong-Ying Cao
- School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Bo Tan
- The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
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Fabisiak A, Włodarczyk J, Fabisiak N, Storr M, Fichna J. Targeting Histamine Receptors in Irritable Bowel Syndrome: A Critical Appraisal. J Neurogastroenterol Motil 2017; 23:341-348. [PMID: 28551943 PMCID: PMC5503283 DOI: 10.5056/jnm16203] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Revised: 03/10/2017] [Accepted: 04/07/2017] [Indexed: 12/19/2022] Open
Abstract
Irritable bowel syndrome is a group of functional gastrointestinal disorders with not yet fully clarified etiology. Recent evidence suggesting that mast cells may play a central role in the pathogenesis of irritable bowel syndrome paves the way for agents targeting histamine receptors as a potential therapeutic option in clinical treatment. In this review, the role of histamine and histamine receptors is debated. Moreover, the clinical evidence of anti-histamine therapeutics in irritable bowel syndrome is discussed.
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Affiliation(s)
- Adam Fabisiak
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz,
Poland
| | - Jakub Włodarczyk
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz,
Poland
| | - Natalia Fabisiak
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz,
Poland
| | - Martin Storr
- Center of Endoscopy, Starnberg,
Germany
- Walter Brendel Center of Experimental Medicine, Ludwig Maximilians University of Munich, Munich,
Germany
| | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz,
Poland
- Correspondence: Jakub Fichna, PhD, DSc, Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland, Tel: +48-42-272-5707, Fax: +48-42-272-5694, E-mail:
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Micucci M, Gotti R, Corazza I, Tocci G, Chiarini A, De Giorgio M, Camarda L, Frosini M, Marzetti C, Cevenini M, Budriesi R. Newer Insights into the Antidiarrheal Effects of Acacia catechu Willd. Extract in Guinea Pig. J Med Food 2017; 20:592-600. [DOI: 10.1089/jmf.2016.0154] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Affiliation(s)
- Matteo Micucci
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum—University of Bologna, Bologna, Italy
| | - Roberto Gotti
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum—University of Bologna, Bologna, Italy
| | - Ivan Corazza
- Department of Experimental, Diagnostic and Speciality Medicine, Alma Mater Studiorum—University of Bologna, Bologna, Italy
| | | | - Alberto Chiarini
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum—University of Bologna, Bologna, Italy
| | - Marta De Giorgio
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum—University of Bologna, Bologna, Italy
| | - Luca Camarda
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum—University of Bologna, Bologna, Italy
| | - Maria Frosini
- Department of Life Sciences, University of Siena, Siena, Italy
| | | | - Monica Cevenini
- Departiment of Medical and Surgical Sciences, Alma Mater Studiorum—University of Bologna, Bologna, Italy
| | - Roberta Budriesi
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum—University of Bologna, Bologna, Italy
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10
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11
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Guarino MPL, Cicala M, Putignani L, Severi C. Gastrointestinal neuromuscular apparatus: An underestimated target of gut microbiota. World J Gastroenterol 2016; 22:9871-9879. [PMID: 28018095 PMCID: PMC5143755 DOI: 10.3748/wjg.v22.i45.9871] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Revised: 10/13/2016] [Accepted: 11/14/2016] [Indexed: 02/06/2023] Open
Abstract
Over the last few years, the importance of the resident intestinal microbiota in the pathogenesis of several gastro-intestinal diseases has been largely investigated. Growing evidence suggest that microbiota can influence gastro-intestinal motility. The current working hypothesis is that dysbiosis-driven mucosal alterations induce the production of several inflammatory/immune mediators which affect gut neuro-muscular functions. Besides these indirect mucosal-mediated effects, the present review highlights that recent evidence suggests that microbiota can directly affect enteric nerves and smooth muscle cells functions through its metabolic products or bacterial molecular components translocated from the intestinal lumen. Toll-like receptors, the bacterial recognition receptors, are expressed both on enteric nerves and smooth muscle and are emerging as potential mediators between microbiota and the enteric neuromuscular apparatus. Furthermore, the ongoing studies on probiotics support the hypothesis that the neuromuscular apparatus may represent a target of intervention, thus opening new physiopathological and therapeutic scenarios.
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