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Current Reviews in Clinical and Experimental Pharmacology

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ISSN (Print): 2772-4328
ISSN (Online): 2772-4336

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A Review of Preclinical Tools to Validate Anti-Diarrheal Agents

Author(s): Rajdeep Sarma, Anshul Shakya*, Arka Karmakar, Surajit Kumar Ghosh, Hans Raj Bhat, Neha Ghimire and Obaidur Rahman

Volume 19, Issue 1, 2024

Published on: 08 December, 2022

Page: [12 - 25] Pages: 14

DOI: 10.2174/2772432818666221121113622

Price: $65

Abstract

Background: Since their inception, preclinical experimental models have played an important role in investigating and characterizing disease pathogenesis. These in vivo, ex vivo, and in vitro preclinical tests also aid in identifying targets, evaluating potential therapeutic drugs, and validating treatment protocols.

Introduction: Diarrhea is a leading cause of mortality and morbidity, particularly among children in developing countries, and it represents a huge health-care challenge on a global scale. Due to its chronic manifestations, alternative anti-diarrheal medications must be tested and developed because of the undesirable side effects of currently existing anti-diarrheal drugs.

Methods: Several online databases, including Science Direct, PubMed, Web of Science, Google Scholar and Scopus, were used in the literature search. The datasets were searched for entries of studies up to May, 2022.

Results: The exhaustive literature study provides a large number of in vivo, in vitro and ex vivo models, which have been used for evaluating the mechanism of the anti-diarrheal effect of drugs in chemically-, pathogen-, disease-induced animal models of diarrhea. The advances and challenges of each model were also addressed in this review.

Conclusion: This review encompasses diverse strategies for screening drugs with anti-diarrheal effects and covers a wide range of pathophysiological and molecular mechanisms linked to diarrhea, with a particular emphasis on the challenges of evaluating and predictively validating these experimental models in preclinical studies. This could also help researchers find a new medicine to treat diabetes more effectively and with fewer adverse effects.

Keywords: Animal model, diarrhea, anti-diarrheal drugs, in vivo, in vitro, ex vivo.

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[1]
Kumar B, Divakar K, Tiwari P, Salhan M, Goli D. Evaluation of anti-diarrhoeal effect of aqueous and ethanolic extracts of fruit pulp of Terminalia belerica in rats. Int J Drug Dev Res 2010; 2(4): 769-79.
[2]
Camilleri M, Sellin JH, Barrett KE. Pathophysiology, evaluation, and management of chronic watery diarrhea. Gastroenterology 2017; 152(3): 515-32.
[http://dx.doi.org/10.1053/j.gastro.2016.10.014] [PMID: 27773805]
[3]
Shahed-Al-Mahmud M, Jahan T, Towhidul Islam M. Antidiarrheal activities of hydroalcoholic extract of Sida cordifolia roots in Wister albino rats. Orient Pharm Exp Med 2018; 18(1): 51-8.
[http://dx.doi.org/10.1007/s13596-017-0295-5]
[4]
Whyte LA, Jenkins HR. Pathophysiology of diarrhoea. Paediatr Child Health 2012; 22(10): 443-7.
[http://dx.doi.org/10.1016/j.paed.2012.05.006]
[5]
Lakshminarayana M, Shivkumar H, Rimaben P, Bhargava V. Antidiarrhoeal activity of leaf extract of Moringa oleifera in experimentally induced diarrhoea in rats. Int J Phytomed 2011; 3(1): 68.
[6]
Calzada F, Juárez T, García-Hernández N, et al. Antiprotozoal, antibacterial and antidiarrheal properties from the flowers of Chiranthodendron pentadactylon and isolated flavonoids. Pharmacogn Mag 2017; 13(50): 240-4.
[http://dx.doi.org/10.4103/0973-1296.204564] [PMID: 28539715]
[7]
Molla M, Gemeda N, Abay SM. Investigating potential modes of actions of Mimusops kummel fruit extract and solvent fractions for their antidiarrheal activities in mice. Evid Based Complement Alternat Med 2017; 2017: 1-11.
[http://dx.doi.org/10.1155/2017/4103410]
[8]
Komal KS, Rana A. Herbal approaches for diarrhoea: A review. Int Res J Pharm 2013; 4(1): 31-8.
[9]
Suleiman MM, Oyelowo BB, Abubakar A, Mamman M, Bello KT. A controlled study to investigate anti-diarrhoeal effect of the stem-bark fractions of Terminalia avicennioides in laboratory animal models. Int J Vet Sci Med 2017; 5(1): 14-22.
[http://dx.doi.org/10.1016/j.ijvsm.2017.04.002] [PMID: 30255043]
[10]
Shakya A, Chaudhary SK, Bhat HR, Ghosh SK. Acute and sub-chronic toxicity studies of Benincasa hispida (Thunb.) cogniaux fruit extract in rodents. Regul Toxicol Pharmacol 2020; 118: 104785.
[http://dx.doi.org/10.1016/j.yrtph.2020.104785] [PMID: 32976857]
[11]
Arends MJ, White ES, Whitelaw CBA. Animal and cellular models of human disease. J Pathol 2016; 238(2): 137-40.
[http://dx.doi.org/10.1002/path.4662] [PMID: 26482929]
[12]
Sisay M, Engidawork E, Shibeshi W. Evaluation of the antidiarrheal activity of the leaf extracts of Myrtus communis Linn (Myrtaceae) in mice model. BMC Complement Altern Med 2017; 17(1): 103.
[http://dx.doi.org/10.1186/s12906-017-1625-3] [PMID: 28183311]
[13]
Emudainohwo JO, Moke GE, Ejebe DE, Earnest O. An investigation into the anti-diarrhoeal effects of aqueous and ethanol stem bark extracts of Alchornea cordifolia in Wistar rats. J Pharmacogn Phytochem 2015; 4(1): 183-7.
[14]
Shahed-Al-Mahmud M, Shawon MJA, Islam T, Rahman MM, Rahman MR. In vivo anti-diarrheal activity of methanolic extract of Streblus asper leaves stimulating the Na+/K+-ATPase in Swiss albino rats. Indian J Clin Biochem 2020; 35(1): 72-9.
[http://dx.doi.org/10.1007/s12291-018-0781-7] [PMID: 32071498]
[15]
Aleem A, Janbaz KH. Ethnopharmacological evaluation of Cenchrus ciliaris for multiple gastrointestinal disorders. Bangladesh J Pharmacol 2017; 12(2): 125-32.
[http://dx.doi.org/10.3329/bjp.v12i2.30205]
[16]
Rudra S, Tahamina A, Emon NU, et al. Evaluation of various solvent extracts of Tetrastigma leucostaphylum (Dennst.) Alston leaves, a Bangladeshi traditional medicine used for the treatment of Diarrhea. Molecules 2020; 25(21): 4994.
[http://dx.doi.org/10.3390/molecules25214994] [PMID: 33126608]
[17]
Oghenesuvwe EE, Tedwins EJO, Obiora IS, et al. Preclinical screening techniques for anti-diarrheal drugs: A comprehensive review. Am J Physiol Cell Physiol 2018; 7(2): 61-74.
[18]
Sadraei H, Asghari G, Jamali H. Antidiarrheal action of Zataria multiflora hydroalcoholic and hexane extracts in mice. Journal of Herbmed Pharmacology 2017; 7(1): 22-8.
[http://dx.doi.org/10.15171/jhp.2018.05]
[19]
Ahmad S, Nasrin MS, Reza ASMA, et al. Curculigo recurvata W.T.Aiton exhibits anti‐nociceptive and anti‐diarrheal effects in Albino mice and an in silico model. Animal Model Exp Med 2020; 3(2): 169-81.
[http://dx.doi.org/10.1002/ame2.12119] [PMID: 32613176]
[20]
Afroz S, Alamgir M, Khan MTH, Jabbar S, Nahar N, Choudhuri MSK. Antidiarrhoeal activity of the ethanol extract of Paederia foetida Linn. (Rubiaceae). J Ethnopharmacol 2006; 105(1-2): 125-30.
[http://dx.doi.org/10.1016/j.jep.2005.10.004] [PMID: 16298094]
[21]
Ramdas P, Sangameswaran B, Gaurav B, Pramod D, Vinayak D. Antidiarrheal potential of Adenanthera pavonina Linn seed aqueous extract in experimental animals. Int J Clin Med 2017; 1(4): 116-20.
[22]
Prashant B, Shamkuwar S, Shahi R. Evaluation of antidiarrhoeal activity of mebarid: An ayurvedic formulation. Int J Pharm Pharm Sci 2012; 4(2): 714-6.
[23]
Abraham B, Sellin JH. Drug-induced diarrhea. Curr Gastroenterol Rep 2007; 9(5): 365-72.
[http://dx.doi.org/10.1007/s11894-007-0044-x] [PMID: 17991336]
[24]
Ratnaike RN, Jones TE. Mechanisms of drug-induced diarrhoea in the elderly. Drugs Aging 1998; 13(3): 245-53.
[http://dx.doi.org/10.2165/00002512-199813030-00007] [PMID: 9789728]
[25]
Bimlesh K, Kalyani D, Prashant T, Manoj S, Diwakar G. Evaluation of antidiarrheal effect of aqueous and ethanolic extracts of fruit pulp of Terminalia belerica in rats. Int J Drug Dev Res 2010; 2(4): 769.
[26]
Tuo B, Isenberg JI. Effect of 5-hydroxytryptamine on duodenal mucosal bicarbonate secretion in mice. Gastroenterology 2003; 125(3): 805-14.
[http://dx.doi.org/10.1016/S0016-5085(03)01045-X] [PMID: 12949726]
[27]
Furness JB. Types of neurons in the enteric nervous system. J Auton Nerv Syst 2000; 81(1-3): 87-96.
[http://dx.doi.org/10.1016/S0165-1838(00)00127-2] [PMID: 10869706]
[28]
Gershon MD. Nerves, reflexes, and the enteric nervous system: pathogenesis of the irritable bowel syndrome. J Clin Gastroenterol 2005; 39(5)(S3): S184-93.
[http://dx.doi.org/10.1097/01.mcg.0000156403.37240.30] [PMID: 15798484]
[29]
Gershon MD, Rothman TP. Enteric glia. Glia 1991; 4(2): 195-204.
[http://dx.doi.org/10.1002/glia.440040211] [PMID: 1827778]
[30]
Kadowaki M, Gershon MD, Kuwahara A. Is nitric oxide involved in 5-HT-induced fluid secretion in the gut? Behav Brain Res 1995; 73(1-2): 293-6.
[http://dx.doi.org/10.1016/0166-4328(96)00126-X] [PMID: 8788522]
[31]
Benson AB III, Ajani JA, Catalano RB, et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 2004; 22(14): 2918-26.
[http://dx.doi.org/10.1200/JCO.2004.04.132] [PMID: 15254061]
[32]
Gibson RJ, Stringer AM. Chemotherapy-induced diarrhoea. Curr Opin Support Palliat Care 2009; 3(1): 31-5.
[http://dx.doi.org/10.1097/SPC.0b013e32832531bb] [PMID: 19365159]
[33]
Ikuno N, Soda H, Watanabe M, Oka M. Irinotecan (CPT-11) and characteristic mucosal changes in the mouse ileum and cecum. J Natl Cancer Inst 1995; 87(24): 1876-83.
[http://dx.doi.org/10.1093/jnci/87.24.1876] [PMID: 7494232]
[34]
Vincenzi B, Schiavon G, Pantano F, Santini D, Tonini G. Predictive factors for chemotherapy-related toxic effects in patients with colorectal cancer. Nat Clin Pract Oncol 2008; 5(8): 455-65.
[http://dx.doi.org/10.1038/ncponc1137] [PMID: 18542119]
[35]
Stringer AM, Gibson RJ, Logan RM, Bowen JM, Yeoh ASJ, Keefe DMK. Faecal microflora and β-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats. Cancer Biol Ther 2008; 7(12): 1919-25.
[http://dx.doi.org/10.4161/cbt.7.12.6940] [PMID: 18927500]
[36]
Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: A double-blind, randomised, placebo-controlled phase III trial. Lancet 2008; 372(9637): 449-56.
[http://dx.doi.org/10.1016/S0140-6736(08)61039-9] [PMID: 18653228]
[37]
Gore ME, Szczylik C, Porta C, et al. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: An expanded-access trial. Lancet Oncol 2009; 10(8): 757-63.
[http://dx.doi.org/10.1016/S1470-2045(09)70162-7] [PMID: 19615940]
[38]
Klee WA, Sharma SK, Nirenberg M. Opiate receptors as regulators of adenylate cyclase. Life Sci 1975; 16(12): 1869-74.
[http://dx.doi.org/10.1016/0024-3205(75)90293-3] [PMID: 168448]
[39]
Gintzler AR. Serotonin participation in gut withdrawal from opiates. J Pharmacol Exp Ther 1979; 211(1): 7-12.
[PMID: 573789]
[40]
Beubler E, Bukhave K, Rask-Madsen J. Colonic secretion mediated by prostaglandin E2 and 5-hydroxytryptamine may contribute to diarrhea due to morphine withdrawal in the rat. Gastroenterology 1984; 87(5): 1042-8.
[http://dx.doi.org/10.1016/S0016-5085(84)80063-3] [PMID: 6090256]
[41]
Nataro JP, Kaper JB. Diarrheagenic Escherichia coli. Clin Microbiol Rev 1998; 11(1): 142-201.
[http://dx.doi.org/10.1128/CMR.11.1.142] [PMID: 9457432]
[42]
Zhao RS, Yang HS, Hao JS, Mao ZQ, Zhao YE. coli O111 was used to induce mouse diarrhea model. J Animal Sci Vet Med 2002; 2: 85-5.
[43]
Yu J, Zhang Y, Song X, et al. Effect of modified pulsatilla powder on enterotoxigenic Escherichia coli O101-induced diarrhea in mice. Evid-Bas Compl Alt Med 2017; 2017: 11.
[http://dx.doi.org/10.1155/2017/3687486]
[44]
Jayshree DP, Devang KP, Anshu S, Vipin K. Screening of plant extracts used in traditional antidiarrheal medicines against pathogenic Escherichia coli. Sci World J 2008; 6(6): 63-7.
[45]
Abbasi E, Mondanizadeh M, van Belkum A, Ghaznavi-Rad E. Multi-drug-resistant diarrheagenic Escherichia coli pathotypes in pediatric patients with gastroenteritis from central Iran. Infect Drug Resist 2020; 13: 1387-96.
[http://dx.doi.org/10.2147/IDR.S247732] [PMID: 32523359]
[46]
Robins-Browne RM, Hartland EL. Escherichia coli as a cause of diarrhea. J Gastroenterol Hepatol 2002; 17(4): 467-75.
[http://dx.doi.org/10.1046/j.1440-1746.2002.02769.x] [PMID: 11982729]
[47]
Gomes TAT, Elias WP, Scaletsky ICA, et al. Diarrheagenic Escherichia coli. Braz J Microbiol 2016; 47(S1): 3-30.
[http://dx.doi.org/10.1016/j.bjm.2016.10.015] [PMID: 27866935]
[48]
DuPont HL, Formal SB, Hornick RB, et al. Pathogenesis of Escherichia coli diarrhea. N Engl J Med 1971; 285(1): 1-9.
[http://dx.doi.org/10.1056/NEJM197107012850101] [PMID: 4996788]
[49]
Ghai OP, Menon PSN, Bhau MK. Pathogenesis of diarrhea due to Escherichia coli. Indian J Pediatr 1980; 47(4): 311-6.
[http://dx.doi.org/10.1007/BF02831325] [PMID: 7014432]
[50]
Wambe H, Noubissi P A, Fokam TMA, et al. Anti-shigellosis activity of Cola anomala water/ethanol pods extract on Shigella flexneri-induced diarrhea in rats. BioMed Res Int 2019; 2019.
[51]
Noubissi PA, Fokam TMA, Fankem GO, Ngakou MJ, Wambe H, Kamgang R. Effects of Crinum jagus water/ethanol extract on Shigella flexneri-induced diarrhea in rats. Evid Based Complement Alternat Med 2019; 2019: 1-10.
[52]
Ramamurthy T, Nandy RK, Mukhopadhyay AK, et al. Virulence regulation and innate host response in the pathogenicity of Vibrio cholerae. Front Cell Infect Microbiol 2020; 10: 572096.
[http://dx.doi.org/10.3389/fcimb.2020.572096] [PMID: 33102256]
[53]
Ogura K, Yahiro K, Moss J. Cell death signaling pathway induced by cholix toxin, a cytotoxin and eEF2 ADP-ribosyltransferase produced by Vibrio cholerae. Toxins 2020; 13(1): 12.
[http://dx.doi.org/10.3390/toxins13010012] [PMID: 33374361]
[54]
Vezzulli L, Baker-Austin C, Kirschner A, Pruzzo C, Martinez-Urtaza J. Global emergence of environmental non‐O1/O139 Vibrio cholerae infections linked with climate change: A neglected research field? Environ Microbiol 2020; 22(10): 4342-55.
[http://dx.doi.org/10.1111/1462-2920.15040] [PMID: 32337781]
[55]
Troeger C, Forouzanfar M, Rao PC, et al. Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: A systematic analysis for the Global Burden of Disease Study 2015. Lancet Infect Dis 2017; 17(9): 909-48.
[http://dx.doi.org/10.1016/S1473-3099(17)30276-1] [PMID: 28579426]
[56]
Crump JA, Sjölund-Karlsson M, Gordon MA, Parry CM. Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive Salmonella infections. Clin Microbiol Rev 2015; 28(4): 901-37.
[http://dx.doi.org/10.1128/CMR.00002-15] [PMID: 26180063]
[57]
Knodler LA, Elfenbein JR. Salmonella enterica. Trends Microbiol 2019; 27(11): 964-5.
[http://dx.doi.org/10.1016/j.tim.2019.05.002] [PMID: 31160162]
[58]
Peng Z, Ling L, Stratton CW, et al. Advances in the diagnosis and treatment of Clostridium difficile infections. Emerg Microbes Infect 2018; 7(1): 1-13.
[http://dx.doi.org/10.1038/s41426-017-0019-4] [PMID: 29434201]
[59]
Mileto SJ, Jardé T, Childress KO, et al. Clostridioides difficile infection damages colonic stem cells via TcdB, impairing epithelial repair and recovery from disease. Proc Natl Acad Sci 2020; 117(14): 8064-73.
[http://dx.doi.org/10.1073/pnas.1915255117] [PMID: 32198200]
[60]
Androga GO, Hart J, Foster NF, Charles A, Forbes D, Riley TV. Infection with toxin A-negative, toxin B-negative, binary toxin-positive Clostridium difficile in a young patient with ulcerative colitis. J Clin Microbiol 2015; 53(11): 3702-4.
[http://dx.doi.org/10.1128/JCM.01810-15] [PMID: 26354812]
[61]
Darkoh C, Plants-Paris K, Bishoff D, DuPont HL. Clostridium difficile modulates the gut microbiota by inducing the production of indole, an interkingdom signaling and antimicrobial molecule. mSystems 2019; 4(2): e00346-18.
[http://dx.doi.org/10.1128/mSystems.00346-18] [PMID: 30944877]
[62]
Quesada-Gómez C, López-Ureña D, Acuña-Amador L, et al. Emergence of an outbreak-associated Clostridium difficile variant with increased virulence. J Clin Microbiol 2015; 53(4): 1216-26.
[http://dx.doi.org/10.1128/JCM.03058-14] [PMID: 25653402]
[63]
Awoyeni A, Olaniran O, Odetoyin B, et al. Isolation and evaluation of Candida species and their association with CD4+ T cells counts in HIV patients with diarrhoea. Afr Health Sci 2017; 17(2): 322-9.
[http://dx.doi.org/10.4314/ahs.v17i2.5] [PMID: 29062326]
[64]
Nobile CJ, Johnson AD. Candida albicans biofilms and human disease. Annu Rev Microbiol 2015; 69(1): 71-92.
[http://dx.doi.org/10.1146/annurev-micro-091014-104330] [PMID: 26488273]
[65]
Panpetch W, Hiengrach P, Nilgate S, et al. Additional Candida albicans administration enhances the severity of dextran sulfate solution induced colitis mouse model through leaky gut-enhanced systemic inflammation and gut-dysbiosis but attenuated by Lactobacillus rhamnosus L34. Gut Microbes 2020; 11(3): 465-80.
[http://dx.doi.org/10.1080/19490976.2019.1662712] [PMID: 31530137]
[66]
Gantner BN, Simmons RM, Underhill DM. Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J 2005; 24(6): 1277-86.
[http://dx.doi.org/10.1038/sj.emboj.7600594] [PMID: 15729357]
[67]
Goodgame RW. Viral causes of diarrhea. Gastroenterol Clin North Am 2001; 30(3): 779-95.
[http://dx.doi.org/10.1016/S0889-8553(05)70210-7] [PMID: 11586557]
[68]
Tafazoli F, Zeng CQ, Estes MK, Magnusson KE, Svensson L. NSP4 enterotoxin of rotavirus induces paracellular leakage in polarized epithelial cells. J Virol 2001; 75(3): 1540-6.
[http://dx.doi.org/10.1128/JVI.75.3.1540-1546.2001] [PMID: 11152526]
[69]
Morris AP, Scott JK, Ball JM, Zeng CQ-Y, O’Neal WK, Estes MK. NSP4 elicits age-dependent diarrhea and Ca(2+)mediated I(-) influx into intestinal crypts of CF mice. Am J Physiol 1999; 277(2): G431-44.
[PMID: 10444458]
[70]
Crawford SE, Ramani S, Tate JE, et al. Rotavirus infection. Nat Rev Dis Primers 2017; 3(1): 17083.
[http://dx.doi.org/10.1038/nrdp.2017.83] [PMID: 29119972]
[71]
Tang Y, Forsyth CB, Keshavarzian A. New molecular insights into inflammatory bowel disease-induced diarrhea. Expert Rev Gastroenterol Hepatol 2011; 5(5): 615-25.
[http://dx.doi.org/10.1586/egh.11.64] [PMID: 21910579]
[72]
Ivanov AI, Parkos CA, Nusrat A. Cytoskeletal regulation of epithelial barrier function during inflammation. Am J Pathol 2010; 177(2): 512-24.
[http://dx.doi.org/10.2353/ajpath.2010.100168] [PMID: 20581053]
[73]
Zhang L, Liu F, Xue J, Lee SA, Liu L, Riordan SM. Bacterial species associated with human inflammatory bowel disease and their pathogenic mechanisms. Front Microbiol 2022; 13: 801892.
[http://dx.doi.org/10.3389/fmicb.2022.801892] [PMID: 35283816]
[74]
Wu LH, Xu ZL, Dong D, He SA, Yu H. Protective effect of anthocyanins extract from blueberry on TNBS-In duce d IBD model of mice. Evid Based Complement Alternat Med 2011; 2011: 1-8.
[http://dx.doi.org/10.1093/ecam/neq040] [PMID: 21785630]
[75]
Roth S, Spalinger MR, Müller I, Lang S, Rogler G, Scharl M. Bilberry-derived anthocyanins prevent IFN-γ-induced pro-inflammatory signalling and cytokine secretion in human THP-1 monocytic cells. Digestion 2014; 90(3): 179-89.
[http://dx.doi.org/10.1159/000366055] [PMID: 25401758]
[76]
Barrett KE, Keely SJ. Chloride secretion by the intestinal epithelium: molecular basis and regulatory aspects. Annu Rev Physiol 2000; 62(1): 535-72.
[http://dx.doi.org/10.1146/annurev.physiol.62.1.535] [PMID: 10845102]
[77]
Florentin D, Sassi A, Roques BP. A highly sensitive fluorometric assay for “enkephalinase”, a neutral metalloendopeptidase that releases tyrosine-glycine-glycine from enkephalins. Anal Biochem 1984; 141(1): 62-9.
[http://dx.doi.org/10.1016/0003-2697(84)90425-1] [PMID: 6388410]
[78]
Schwartz JC, Malfroy B, De La Baume S. Biological inactivation of enkephalins and the role of enkephalin-dipeptidyl-carboxypeptidase (“enkephalinase”) as neuropeptidase. Life Sci 1981; 29(17): 1715-40.
[http://dx.doi.org/10.1016/0024-3205(81)90182-X] [PMID: 6272046]
[79]
Thiagarajah JR, Ko EA, Tradtrantip L, Donowitz M, Verkman AS. Discovery and development of antisecretory drugs for treating diarrheal diseases. Clin Gastroenterol Hepatol 2014; 12(2): 204-9.
[http://dx.doi.org/10.1016/j.cgh.2013.12.001] [PMID: 24316107]
[80]
Schulzke JD, Andres S, Amasheh M, Fromm A, Günzel D. Anti-diarrheal mechanism of the traditional remedy Uzara via reduction of active chloride secretion. PLoS One 2011; 6(3): e18107.
[http://dx.doi.org/10.1371/journal.pone.0018107] [PMID: 21479205]
[81]
Tradtrantip L, Namkung W, Verkman AS. Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol 2010; 77(1): 69-78.
[http://dx.doi.org/10.1124/mol.109.061051] [PMID: 19808995]
[82]
Kelly OB, Mroz MS, Ward JBJ, et al. Ursodeoxycholic acid attenuates colonic epithelial secretory function. J Physiol 2013; 591(9): 2307-18.
[http://dx.doi.org/10.1113/jphysiol.2013.252544] [PMID: 23507881]
[83]
Keely SJ, Walters JRF. The farnesoid X receptor: Good for BAD. Cell Mol Gastroenterol Hepatol 2016; 2(6): 725-32.
[http://dx.doi.org/10.1016/j.jcmgh.2016.08.004] [PMID: 28174746]
[84]
Greig ER, Boot-Handford RP, Mani V, Sandle GI. Decreased expression of apical Na+ channels and basolateral Na+, K+-ATPase in ulcerative colitis. J Pathol 2004; 204(1): 84-92.
[http://dx.doi.org/10.1002/path.1613] [PMID: 15307141]
[85]
Kiela PR, Xu H, Ghishan FK. Apical NA+/H+ exchangers in the mammalian gastrointestinal tract. J Physiol Pharmacol 2006; 57 (Suppl. 7): 51-79.
[PMID: 17228096]
[86]
Kiela P, Ghishan F. Na+-H+ exchange in mammalian digestive tract Physiology of the Gastrointestinal Tract. Elsevier Press: Amsterdam, Netherlands 2006.
[http://dx.doi.org/10.1016/B978-012088394-3/50076-3]
[87]
Khan I, al-Awadi FM, Abul H. Colitis-induced changes in the expression of the Na+/H+ exchanger isoform NHE-1. J Pharmacol Exp Ther 1998; 285(2): 869-75.
[PMID: 9580638]
[88]
Firsov D, Gautschi I, Merillat A-M, Rossier BC, Schild L. The heterotetrameric architecture of the epithelial sodium channel (ENaC). EMBO J 1998; 17(2): 344-52.
[http://dx.doi.org/10.1093/emboj/17.2.344] [PMID: 9430626]
[89]
Greig E, Sandle G. Diarrhea in ulcerative colitis. The role of altered colonic sodium transport. Ann N Y Acad Sci 2000; 915(1): 327-32.
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb05260.x] [PMID: 11193595]
[90]
Zeissig S, Bergann T, Fromm A, et al. Altered ENaC expression leads to impaired sodium absorption in the noninflamed intestine in Crohn’s disease. Gastroenterology 2008; 134(5): 1436-47.
[http://dx.doi.org/10.1053/j.gastro.2008.02.030] [PMID: 18355814]
[91]
Vickers NJ. Animal communication: When i’m calling you, will you answer too? Curr Biol 2017; 27(14): R713-5.
[http://dx.doi.org/10.1016/j.cub.2017.05.064] [PMID: 28743020]
[92]
Khan I, Siddique I, Al-Awadi FM, Mohan K. Role of Na+/H+ exchanger isoform-1 in human inflammatory bowel disease. Can J Gastroenterol 2003; 17(1): 31-6.
[http://dx.doi.org/10.1155/2003/673819] [PMID: 12560852]
[93]
Taylor AF, Saunders MM, Shingle DL, Cimbala JM, Zhou Z, Donahue HJ. Mechanically stimulated osteocytes regulate osteoblastic activity via gap junctions. Am J Physiol Cell Physiol 2007; 292(1): C545-52.
[http://dx.doi.org/10.1152/ajpcell.00611.2005] [PMID: 16885390]
[94]
Gilani AH, Khan A, Raoof M, et al. Gastrointestinal, selective airways and urinary bladder relaxant effects of Hyoscyamus niger are mediated through dual blockade of muscarinic receptors and Ca2+ channels. Fundam Clin Pharmacol 2008; 22(1): 87-99.
[http://dx.doi.org/10.1111/j.1472-8206.2007.00561.x] [PMID: 18251725]
[95]
Saikia B, Barua CC, Haloi P, Patowary P. Anticholinergic, antihistaminic, and antiserotonergic activity of n-hexane extract of Zanthoxylum alatum seeds on isolated tissue preparations: An ex vivo study. Indian J Pharmacol 2017; 49(1): 42-8.
[PMID: 28458421]
[96]
Khosroukhavar R, Ahmadiani A, Shamsa F. Antihistaminic and anticholinergic activity of methanolic extract of barberry fruit (Berberis vulgaris) in the guinea-pig ileum. Faslnamah-i Giyahan-i Daruyi 2010; 9(35): 99-105.
[97]
Khan H, Saeed M, Gilani AH, et al. Antispasmodic and antidiarrheal activities of rhizomes of Polygonatum verticillatum maneuvered predominately through activation of K+ channels. Toxicol Ind Health 2016; 32(4): 677-85.
[http://dx.doi.org/10.1177/0748233713506956] [PMID: 24215061]
[98]
Mahmood H, Chaudhry MA, Masood Z, Saeed MA, Adnan S. A mechanistic evaluation of the traditional uses of Nepeta ruderalis in gastrointestinal and airway disorders. Pharm Biol 2017; 55(1): 1017-21.
[http://dx.doi.org/10.1080/13880209.2017.1285325] [PMID: 28183233]

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