Generic placeholder image

Current Reviews in Clinical and Experimental Pharmacology

Editor-in-Chief

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

Mini-Review Article

Application of Drug Repurposing Approach for Therapeutic Intervention of Inflammatory Bowel Disease

Author(s): Mohammad Aadil Bhat, Iqra Usman and Suneela Dhaneshwar*

Volume 19, Issue 3, 2024

Published on: 18 October, 2023

Page: [234 - 249] Pages: 16

DOI: 10.2174/0127724328245156231008154045

Price: $65

Abstract

Inflammatory bowel disease (IBD), represented by Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract (GIT) characterized by chronic relapsing intestinal inflammation, abdominal pain, cramping, loss of appetite, fatigue, diarrhoea, and weight loss. Although the etiology of IBD remains unclear, it is believed to be an interaction between genes, and environmental factors, such as an imbalance of the intestinal microbiota, changing food habits, an ultra-hygiene environment, and an inappropriate immune system. The development of novel effective therapies is stymied by a lack of understanding of the aetiology of IBD. The current therapy involves the use of aminosalicylates, immunosuppressants, and corticosteroids that can effectively manage symptoms, induce and sustain remission, prevent complications, modify the course of the disease, provide diverse treatment options, showcase advancements in biologic therapies, and enhance the overall quality of life. However, the efficacy of current therapy is overshadowed by a plethora of adverse effects, such as loss of weight, mood swings, skin issues, loss of bone density, higher vulnerability to infections, and elevated blood pressure. Biologicals, like anti-tumour necrosis factor agents, can stimulate an autoimmune response in certain individuals that may diminish the effectiveness of the medication over time, necessitating a switch to alternative treatments. The response of IBD patients to current drug therapy is quite varied, which can lead to disease flares that underlines the urgent need to explore alternative treatment option to address the unmet need of developing new treatment strategies for IBD with high efficacy and fewer adverse effects. Drug repurposing is a novel strategy where existing drugs that have already been validated safe in patients for the management of certain diseases are redeployed to treat other, unindicated diseases. The present narrative review focuses on potential drug candidates that could be repurposed for the management of IBD using on-target and off-target strategies. It covers their preclinical, clinical assessment, mechanism of action, and safety profiles, and forecasts their appropriateness in the management of IBD. The review presents useful insights into the most promising candidates for repurposing, like anti-inflammatory and anti-apoptotic troxerutin, which has been found to improve the DSS-induced colitis in rats, an antiosteoarthritic drug diacetylrhein that has been found to have remarkable ameliorating effects on DSS-induced colitis via anti-oxidant and anti- inflammatory properties and by influencing both apoptosis and pyroptosis. Topiramate, an antiepileptic and anticonvulsant drug, has remarkably decreased overall pathophysiological and histopathological events in the experimental model of IBD in rodents by its cytokine inhibitory action.

Keywords: Drug repositioning, drug reprofiling, drug redirecting, drug rediscovery, colonic inflammation, large intestine, IBD, CD, UC.

Graphical Abstract
[1]
Cai Z, Wang S, Li J. Treatment of inflammatory bowel disease: A comprehensive review. Front Med (Lausanne) 2021; 8(December): 765474.
[http://dx.doi.org/10.3389/fmed.2021.765474] [PMID: 34988090]
[2]
Ramos GP, Papadakis KA. Mechanisms of disease: Inflammatory bowel diseases. Mayo Clin Proc 2019; 94(1): 155-65.
[http://dx.doi.org/10.1016/j.mayocp.2018.09.013] [PMID: 30611442]
[3]
Baumgart DC, Carding SR. Series Gastroenterology 1 Infl ammatory bowel disease : Cause and immunobiology. Lancet 2007; 369: 1627-40.
[http://dx.doi.org/10.1016/S0140-6736(07)60750-8] [PMID: 17499605]
[4]
Seyedian SS, Nokhostin F, Malamir MD. A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. J Med Life 2019; 12(2): 113-22.
[http://dx.doi.org/10.25122/jml-2018-0075]
[5]
Burgmann T, Clara I, Graff L, et al. The Manitoba Inflammatory Bowel Disease Cohort Study: Prolonged symptoms before diagnosis--how much is irritable bowel syndrome? Clin Gastroenterol Hepatol 2006; 4(5): 614-20.
[http://dx.doi.org/10.1016/j.cgh.2006.03.003] [PMID: 16630762]
[6]
Pithadia AB, Jain S. Treatment of inflammatory bowel disease (IBD). In: Pharmacological reports. Elsevier BV. 2011; 63: pp. 629-42.
[7]
Roy S, Dhaneshwar S. Drug repurposing opportunities for inflammatory bowel disease 2018.http://meddocsonline.org/ ebooks/inflammatory-bowel-disease/drug-repurposing-opportunities-for-inflammatory-bowel-disease.pdf
[8]
Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review Gastroenterology 2012; 142(1): 46-54.e4.https://www.sciencedirect.com/science/article/pii/S0016508511013783
[http://dx.doi.org/10.1053/j.gastro.2011.10.001] [PMID: 22001864]
[9]
Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol 2015; 12(12): 720-7.
[http://dx.doi.org/10.1038/nrgastro.2015.150] [PMID: 26323879]
[10]
Duijvestein M, Battat R, Casteele N, et al. Novel therapies and treatment strategies for patients with inflammatory bowel disease. Curr Treat Options Gastroenterol 2018; 16(1): 129-46.
[http://dx.doi.org/10.1007/s11938-018-0175-1] [PMID: 29411220]
[11]
Szigethy E, McLafferty L, Goyal A. Inflammatory bowel disease. Pediatr Clin North Am 2011; 58(4): 903-20. [x-xi.]
[http://dx.doi.org/10.1016/j.pcl.2011.06.007] [PMID: 21855713]
[12]
Sabino J, Verstockt B, Vermeire S, Ferrante M. New biologics and small molecules in inflammatory bowel disease: An update. Therap Adv Gastroenterol 2019; 12.
[http://dx.doi.org/10.1177/1756284819853208] [PMID: 31205488]
[13]
McDonald C, Fiocchi C. Pathophysiology of inflammatory bowel disease. Adv Manag Inflamm Bowel Dis 2013; pp. 19-30.
[14]
Childers RE, Eluri S, Vazquez C, Weise RM, Bayless TM, Hutfless S. Family history of inflammatory bowel disease among patients with ulcerative colitis: A systematic review and meta-analysis. J Crohn’s Colitis 2014; 8(11): 1480-97.
[http://dx.doi.org/10.1016/j.crohns.2014.05.008] [PMID: 24974207]
[15]
Jostins L, Ripke S, Weersma RK, et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012; 491(7422): 119-24.
[http://dx.doi.org/10.1038/nature11582] [PMID: 23128233]
[16]
Guan Q. A comprehensive review and update on the pathogenesis of inflammatory bowel disease. J Immunol Res 2019 2019.
[17]
Zhang YZ, Li YY. Inflammatory bowel disease: Pathogenesis. World J Gastroenterol 2014; 20(1): 91-9.
[http://dx.doi.org/10.3748/wjg.v20.i1.91] [PMID: 24415861]
[18]
de Souza HSP, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol 2016; 13(1): 13-27.
[http://dx.doi.org/10.1038/nrgastro.2015.186] [PMID: 26627550]
[19]
Shaw MH, Kamada N, Warner N, Kim YG, Nuñez G. The ever-expanding function of NOD2: autophagy, viral recognition, and T cell activation. Trends Immunol 2011; 32(2): 73-9.
[http://dx.doi.org/10.1016/j.it.2010.12.007] [PMID: 21251876]
[20]
Noguchi E, Homma Y, Kang X, Netea MG, Ma X. A Crohn’s disease–associated NOD2 mutation suppresses transcription of human IL10 by inhibiting activity of the nuclear ribonucleoprotein hnRNP-A1. Nat Immunol 2009; 10(5): 471-9.
[http://dx.doi.org/10.1038/ni.1722] [PMID: 19349988]
[21]
Hampe J, Franke A, Rosenstiel P, et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 2007; 39(2): 207-11.
[http://dx.doi.org/10.1038/ng1954] [PMID: 17200669]
[22]
Parkes M, Barrett JC, Prescott NJ, et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat Genet 2007; 39(7): 830-2.
[http://dx.doi.org/10.1038/ng2061] [PMID: 17554261]
[23]
Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature 2011; 469(7330): 323-35.
[http://dx.doi.org/10.1038/nature09782] [PMID: 21248839]
[24]
Hornschuh M, Wirthgen E, Wolfien M, Singh KP, Wolkenhauer O, Däbritz J. The role of epigenetic modifications for the pathogenesis of Crohn’s disease. Clin Epigenetics 2021; 13(1): 108.
[http://dx.doi.org/10.1186/s13148-021-01089-3] [PMID: 33980294]
[25]
Nishida A, Inoue R, Inatomi O, Bamba S, Naito Y, Andoh A. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin J Gastroenterol 2018; 11(1): 1-10.
[http://dx.doi.org/10.1007/s12328-017-0813-5] [PMID: 29285689]
[26]
Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 2007; 104(34): 13780-5.www.pnas.org/ cgi/content/full/%0Awww.pnas.org%02cgi%02doi%0210.1073%02pnas.0706625104
[http://dx.doi.org/10.1073/pnas.0706625104] [PMID: 17699621]
[27]
Peterson DA, Frank DN, Pace NR, Gordon JI. Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. Cell Host Microbe 2008; 3(6): 417-27.
[http://dx.doi.org/10.1016/j.chom.2008.05.001] [PMID: 18541218]
[28]
Ananthakrishnan AN, Khalili H, Konijeti GG, et al. A prospective study of long-term intake of dietary fiber and risk of Crohn’s disease and ulcerative colitis. Gastroenterology 2013; 145(5): 970-7.
[http://dx.doi.org/10.1053/j.gastro.2013.07.050] [PMID: 23912083]
[29]
Hou JK, Abraham B, El-Serag H. Dietary intake and risk of developing inflammatory bowel disease: A systematic review of the literature. Am J Gastroenterol 2011; 106(4): 563-73.
[http://dx.doi.org/10.1038/ajg.2011.44] [PMID: 21468064]
[30]
Ananthakrishnan AN, Khalili H, Konijeti GG, et al. Long-term intake of dietary fat and risk of ulcerative colitis and Crohn’s disease. Gut 2014; 63(5): 776-84.
[http://dx.doi.org/10.1136/gutjnl-2013-305304] [PMID: 23828881]
[31]
Ashwin NA, Higuchi LM. Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn. Ann Intern Med 2012; 156(5): 350-9.
[32]
Kvasnovsky CL, Aujla U, Bjarnason I. Nonsteroidal anti-inflammatory drugs and exacerbations of inflammatory bowel disease. Scand J Gastroenterol 2015; 50(3): 255-63.
[http://dx.doi.org/10.3109/00365521.2014.966753] [PMID: 25314574]
[33]
van der Flier LG, Clevers H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 2009; 71(1): 241-60.
[http://dx.doi.org/10.1146/annurev.physiol.010908.163145] [PMID: 18808327]
[34]
Van der Sluis M, De Koning BAE, De Bruijn ACJM, et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 2006; 131(1): 117-29.
[http://dx.doi.org/10.1053/j.gastro.2006.04.020] [PMID: 16831596]
[35]
Fritz T, Niederreiter L, Adolph T, Blumberg RS, Kaser A. Crohn’s disease: NOD2, autophagy and ER stress converge. Gut 2011; 60(11): 1580-8.
[http://dx.doi.org/10.1136/gut.2009.206466] [PMID: 21252204]
[36]
Tian T, Wang Z, Zhang J. Pathomechanisms of oxidative stress in inflammatory bowel disease and potential antioxidant therapies Oxid Med Cell Longev 2017 2017.
[http://dx.doi.org/10.1155/2017/4535194]
[37]
Brazil JC, Louis NA, Parkos CA. The role of polymorphonuclear leukocyte trafficking in the perpetuation of inflammation during inflammatory bowel disease. Inflamm Bowel Dis 2013; 19(7): 1556-65.
[http://dx.doi.org/10.1097/MIB.0b013e318281f54e] [PMID: 23598816]
[38]
Zheng D, Liwinski T, Elinav E. Interaction between microbiota and immunity in health and disease. Cell Res 2020; 30(6): 492-506.
[http://dx.doi.org/10.1038/s41422-020-0332-7] [PMID: 32433595]
[39]
Zenewicz LA, Antov A, Flavell RA. CD4 T-cell differentiation and inflammatory bowel disease. Trends Mol Med 2009; 15(5): 199-207.
[http://dx.doi.org/10.1016/j.molmed.2009.03.002] [PMID: 19362058]
[40]
Fujino S, Andoh A, Bamba S, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut 2003; 52(1): 65-70.
[http://dx.doi.org/10.1136/gut.52.1.65] [PMID: 12477762]
[41]
Biancheri P, Powell N, Monteleone G, Lord G, MacDonald TT. The challenges of stratifying patients for trials in inflammatory bowel disease. Trends Immunol 2013; 34(11): 564-71.
[http://dx.doi.org/10.1016/j.it.2013.08.002] [PMID: 24035478]
[42]
Neurath MF, Schürmann G. Immunopathogenesis of inflammatory bowel diseases. Chirurg 2000; 71(1): 30-40.
[PMID: 10662999]
[43]
Boden EK, Snapper SB. Regulatory T cells in inflammatory bowel disease. Curr Opin Gastroenterol 2008; 24(6): 733-41.
[http://dx.doi.org/10.1097/MOG.0b013e328311f26e] [PMID: 19125486]
[44]
Wirtz S, Neurath M. Mouse models of inflammatory bowel disease. Adv Drug Deliv Rev 2007; 59(11): 1073-83.
[http://dx.doi.org/10.1016/j.addr.2007.07.003] [PMID: 17825455]
[45]
Sanchez-Munoz F, Dominguez-Lopez A, Yamamoto-Furusho J-K. Role of cytokines in inflammatory bowel disease. World J Gastroenterol 2008; 14(27): 4280-8.
[http://dx.doi.org/10.3748/wjg.14.4280]
[46]
Paul A, Anandabaskar N, Mathaiyan J, Raj GM, Eds. Introduction to Basics of Pharmacology and Toxicology: Volume 2: Essentials of Systemic Pharmacology: From Principles to Practice. Springer Singapore 2021; p. p1156.
[47]
Jacob EM, Borah A, Pillai SC, Kumar DS. Inflammatory bowel disease: The emergence of new trends in lifestyle and nanomedicine as the modern tool for pharmacotherapy. Nanomaterials (Basel) 2020; 10(12): 2460.
[http://dx.doi.org/10.3390/nano10122460] [PMID: 33316984]
[48]
Ordás I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet 2012; 380(9853): 1606-19.
[http://dx.doi.org/10.1016/S0140-6736(12)60150-0] [PMID: 22914296]
[49]
Ross H, Steele SR, Varma M, et al. Practice parameters for the surgical treatment of ulcerative colitis. Dis Colon Rectum 2014; 57(1): 5-22.
[http://dx.doi.org/10.1097/DCR.0000000000000030] [PMID: 24316941]
[50]
Askelof E, Helander S. Mechanism of action of 5-arninosalicylic acid. 1992 1992; 151-65.
[51]
Bantel H, Berg C, Vieth M, Stolte M, Kruis W, Schulze-Osthoff K. Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol 2000; 95(12): 3452-7.
[http://dx.doi.org/10.1111/j.1572-0241.2000.03360.x] [PMID: 11151876]
[52]
Rousseaux C, Lefebvre B, Dubuquoy L, et al. Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ. J Exp Med 2005; 201(8): 1205-15.
[http://dx.doi.org/10.1084/jem.20041948] [PMID: 15824083]
[53]
Williams C, Panaccione R, Ghosh S, Rioux K. Optimizing clinical use of mesalazine (5-aminosalicylic acid) in inflammatory bowel disease. Therap Adv Gastroenterol 2011; 4(4): 237-48.
[http://dx.doi.org/10.1177/1756283X11405250] [PMID: 21765868]
[54]
Gisbert JP, González-Lama Y, Maté J. 5-Aminosalicylates and renal function in inflammatory bowel disease. Inflamm Bowel Dis 2007; 13(5): 629-38.
[http://dx.doi.org/10.1002/ibd.20099] [PMID: 17243140]
[55]
Teixeira FV, Hosne RS, Sobrado CW. Management of ulcerative colitis: A clinical update. J Coloproctol (Rio J) 2015; 35(4): 230-7.
[http://dx.doi.org/10.1016/j.jcol.2015.08.006]
[56]
Mowat C, Cole A, Windsor A, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011; 60(5): 571-607.
[http://dx.doi.org/10.1136/gut.2010.224154] [PMID: 21464096]
[57]
Oray M, Abu Samra K, Ebrahimiadib N, Meese H, Foster CS. Long-term side effects of glucocorticoids. Expert Opin Drug Saf 2016; 15(4): 457-65.
[http://dx.doi.org/10.1517/14740338.2016.1140743] [PMID: 26789102]
[58]
Brattsand R, Linden M. Cytokine modulation by glucocorticoids: mechanisms and actions in cellular studies. Aliment Pharmacol Ther 1996; 10 (Suppl. 2): 81-90.
[http://dx.doi.org/10.1046/j.1365-2036.1996.22164025.x] [PMID: 8899106]
[59]
Ramamoorthy S, Cidlowski JA. Corticosteroids. Rheum Dis Clin North Am 2016; 42(1): 15-31. [vii.]
[http://dx.doi.org/10.1016/j.rdc.2015.08.002] [PMID: 26611548]
[60]
Leppert W, Buss T. The role of corticosteroids in the treatment of pain in cancer patients. Curr Pain Headache Rep 2012; 16(4): 307-13.
[http://dx.doi.org/10.1007/s11916-012-0273-z] [PMID: 22644902]
[61]
Cassinotti A, Actis GC, Duca P, et al. Maintenance treatment with azathioprine in ulcerative colitis: Outcome and predictive factors after drug withdrawal. Am J Gastroenterol 2009; 104(11): 2760-7.
[http://dx.doi.org/10.1038/ajg.2009.410] [PMID: 19623172]
[62]
Singh A, Mahajan R, Kedia S, et al. Use of thiopurines in inflammatory bowel disease: An update. Intest Res 2022; 20(1): 11-30.
[http://dx.doi.org/10.5217/ir.2020.00155] [PMID: 33845546]
[63]
Ahmad H, Kumar VL. Pharmacotherapy of ulcerative colitis – current status and emerging trends. J Basic Clin Physiol Pharmacol 2018; 29(6): 581-92.
[http://dx.doi.org/10.1515/jbcpp-2016-0014] [PMID: 30089097]
[64]
Ardizzone S, Cassinotti A, Manes G, Porro G. Review: Immunomodulators for all patients with inflammatory bowel disease? Therap Adv Gastroenterol 2010; 3(1): 31-42.
[http://dx.doi.org/10.1177/1756283X09354136] [PMID: 21180588]
[65]
Naganuma M, Fujii T, Watanabe M. The use of traditional and newer calcineurin inhibitors in inflammatory bowel disease. J Gastroenterol 2011; 46(2): 129-37.
[http://dx.doi.org/10.1007/s00535-010-0352-z] [PMID: 21132334]
[66]
Yoshino T, Nakase H, Honzawa Y, et al. Immunosuppressive effects of tacrolimus on macrophages ameliorate experimental colitis. Inflamm Bowel Dis 2010; 16(12): 2022-33.
[http://dx.doi.org/10.1002/ibd.21318] [PMID: 20848491]
[67]
Léia CRS, Luciena CMO, Gil B. Anti-TNF-(alpha) agents in the treatment of immune-mediated inflammatory diseases: Mechanisms of action and pitfalls. Immunotherapy 2010; 2(6): 817-33.
[68]
Li J, Leng Z, Wu Y, et al. Interactions between invasive plants and heavy metal stresses: a review. J Plant Ecol 2022; 15(3): 429-36.
[http://dx.doi.org/10.1093/jpe/rtab100]
[69]
Gilroy L, Allen PB. Is there a role for vedolizumab in the treatment of ulcerative colitis and Crohn’s disease? Clin Exp Gastroenterol 2014; 7(1): 163-72.
[PMID: 24899819]
[70]
Cai Z, Wang S, Li J. Treatment of inflammatory bowel disease: A comprehensive review. Front Med 2021; 8: 765474.
[http://dx.doi.org/10.3389/fmed.2021.765474] [PMID: 34988090]
[71]
Jonkers D, Penders J, Masclee A, Pierik M. Probiotics in the management of inflammatory bowel disease: A systematic review of intervention studies in adult patients. Drugs 2012; 72(6): 803-23.
[http://dx.doi.org/10.2165/11632710-000000000-00000] [PMID: 22512365]
[72]
Roy S, Dhaneshwar S. Role of prebiotics, probiotics, and synbiotics in management of inflammatory bowel disease: Current perspectives. World J Gastroenterol 2023; 29(14): 2078-100.
[http://dx.doi.org/10.3748/wjg.v29.i14.2078] [PMID: 37122604]
[73]
Langedijk J, Mantel-Teeuwisse AK, Slijkerman DS, Schutjens MHDB. Drug repositioning and repurposing: Terminology and definitions in literature. Drug Discov Today 2015; 20(8): 1027-34.
[http://dx.doi.org/10.1016/j.drudis.2015.05.001] [PMID: 25975957]
[74]
Doan TL, Pollastri M, Walters MA, Georg GI. The future of drug repositioning. Annu Rep Med Chem 2011; 46: 385-401.
[http://dx.doi.org/10.1016/B978-0-12-386009-5.00004-7]
[75]
Wang X, Gao Y, Wang L, et al. Troxerutin improves dextran sulfate sodium-induced ulcerative colitis in mice. J Agric Food Chem 2021; 69(9): 2729-44.
[http://dx.doi.org/10.1021/acs.jafc.0c06755] [PMID: 33621077]
[76]
Schirmer B, Bringmann L, Seifert R, Neumann D. In vivo evidence for partial activation of eosinophils via the histamine H4-receptor: Adoptive transfer experiments using eosinophils from H4R-/- and H4R+/+ mice. Front Immunol 2018; 9: 2119.
[http://dx.doi.org/10.3389/fimmu.2018.02119] [PMID: 30319608]
[77]
Wang X, Wang S, Hu C, et al. A new pharmacological effect of levornidazole: Inhibition of NLRP3 inflammasome activation. Biochem Pharmacol 2015; 97(2): 178-88.
[http://dx.doi.org/10.1016/j.bcp.2015.06.030] [PMID: 26212544]
[78]
Mendes AF, Caramona MM, De Carvalho AP, Lopes MC. Diacerhein and rhein prevent interleukin-1β-induced nuclear factor-kappaB activation by inhibiting the degradation of inhibitor kappaB-α. Pharmacol Toxicol 2002; 91(1): 22-8.
[http://dx.doi.org/10.1034/j.1600-0773.2002.910104.x] [PMID: 12193257]
[79]
Almezgagi M, Zhang Y, Hezam K, et al. Diacerein: Recent insight into pharmacological activities and molecular pathways. Biomed Pharmacother 2020; 131: 110594.
[http://dx.doi.org/10.1016/j.biopha.2020.110594] [PMID: 32858499]
[80]
Zohny MH, Alrouji M, Alhajlah S, et al. Diacetylrhein, an anthraquinone antiarthritic agent, suppresses dextran sodium sulfate-induced inflammation in rats: A possible mechanism for a protective effect against ulcerative colitis. Biomed Pharmacother 2022; 154: 113651.
[http://dx.doi.org/10.1016/j.biopha.2022.113651] [PMID: 36081290]
[81]
Wong RSY. Apoptosis in cancer: From pathogenesis to treatment. J Exp Clin Cancer Res 2011; 30(1): 87.
[http://dx.doi.org/10.1186/1756-9966-30-87] [PMID: 21943236]
[82]
Roy S, Dhaneshwar S, Mahmood T. Exploring the potential of il-1β inhibitor diacerein and its combination with 5-aminosalicylic acid for the possible ameliorating effect in tnbsinduced experimental colitis in wistar rats. Curr Drug Ther 2022; 17(2): 132-46.
[http://dx.doi.org/10.2174/1574885517666220328142715]
[83]
Russo C, Scott KA, Pirmohamed M. Dimethyl fumarate induced lymphopenia in multiple sclerosis: A review of the literature. Pharmacol Ther 2021; 219: 107710.
[http://dx.doi.org/10.1016/j.pharmthera.2020.107710] [PMID: 33091427]
[84]
Blair HA. Dimethyl fumarate: A review in moderate to severe plaque psoriasis. Drugs 2018; 78(1): 123-30.
[http://dx.doi.org/10.1007/s40265-017-0854-6] [PMID: 29236231]
[85]
Linker RA, Lee DH, Ryan S, et al. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain 2011; 134(3): 678-92.
[http://dx.doi.org/10.1093/brain/awq386] [PMID: 21354971]
[86]
Mills EA, Ogrodnik MA, Plave A, Mao-Draayer Y. Emerging understanding of the mechanism of action for dimethyl fumarate in the treatment of multiple sclerosis. Front Neurol 2018; 9(JAN): 5.
[http://dx.doi.org/10.3389/fneur.2018.00005] [PMID: 29410647]
[87]
Patel V, Joharapurkar A, Kshirsagar S, et al. Repurposing dimethyl fumarate for gastric ulcer and ulcerative colitis: Evidence of local efficacy without systemic side effect. Med in Drug Discov 2022; 16: 100142.
[http://dx.doi.org/10.1016/j.medidd.2022.100142]
[88]
Asatsuma-Okumura T, Ito T, Handa H. Molecular mechanisms of the teratogenic effects of thalidomide. Pharmaceuticals 2020; 13(5): 95.
[http://dx.doi.org/10.3390/ph13050095] [PMID: 32414180]
[89]
Miyazato K, Tahara H, Hayakawa Y. Antimetastatic effects of thalidomide by inducing the functional maturation of peripheral natural killer cells. Cancer Sci 2020; 111(8): 2770-8.
[http://dx.doi.org/10.1111/cas.14538] [PMID: 32573072]
[90]
Faver IR, Guerra SG, Su WPD, el-Azhary R. Thalidomide for dermatology: A review of clinical uses and adverse effects. Int J Dermatol 2005; 44(1): 61-7.
[http://dx.doi.org/10.1111/j.1365-4632.2004.02445.x] [PMID: 15663665]
[91]
Vargesson N. Thalidomide-induced teratogenesis: History and mechanisms. Birth Defects Res C Embryo Today 2015; 105(2): 140-56.
[http://dx.doi.org/10.1002/bdrc.21096] [PMID: 26043938]
[92]
Ito T, Handa H. Molecular mechanisms of thalidomide and its derivatives. Proc Jpn Acad, Ser B 2020; 96(6): 189-203.
[http://dx.doi.org/10.2183/pjab.96.016] [PMID: 32522938]
[93]
Holstein SA, McCarthy PL. Immunomodulatory drugs in multiple myeloma: Mechanisms of action and clinical experience. Drugs 2017; 77(5): 505-20.
[http://dx.doi.org/10.1007/s40265-017-0689-1] [PMID: 28205024]
[94]
Okada Y, Murayama N, Yanagida C, Shimizu M, Guengerich FP, Yamazaki H. Drug interactions of thalidomide with midazolam and cyclosporine A: Heterotropic cooperativity of human cytochrome P450 3A5. Drug Metab Dispos 2009; 37(1): 18-23.
[http://dx.doi.org/10.1124/dmd.108.024679] [PMID: 18948377]
[95]
Bramuzzo M, Ventura A, Martelossi S, Lazzerini M. Thalidomide for inflammatory bowel disease. Medicine 2016; 95(30): e4239.
[96]
Carvalho AT, Souza H, Carneiro AJ, et al. Therapeutic and prophylactic thalidomide in TNBS-induced colitis: Synergistic effects on TNF-α IL-12 and VEGF production. World J Gastroenterol 2007; 13(15): 2166-73.
[http://dx.doi.org/10.3748/wjg.v13.i15.2166] [PMID: 17465495]
[97]
Avitzur Y, Guo C, Mastropaolo LA, et al. Mutations in tetratricopeptide repeat domain 7A result in a severe form of very early onset inflammatory bowel disease. Gastroenterology 2014; 146(4): 1028-39.
[http://dx.doi.org/10.1053/j.gastro.2014.01.015] [PMID: 24417819]
[98]
Bigorgne AE, Farin HF, Lemoine R, et al. TTC7A mutations disrupt intestinal epithelial apicobasal polarity. J Clin Invest 2014; 124(1): 328-37.
[http://dx.doi.org/10.1172/JCI71471] [PMID: 24292712]
[99]
Jardine S, Dhingani N, Muise AM. TTC7A: Steward of intestinal health. Cell Mol Gastroenterol Hepatol 2019; 7(3): 555-70.
[http://dx.doi.org/10.1016/j.jcmgh.2018.12.001] [PMID: 30553809]
[100]
Lien R, Lin YF, Lai MW, et al. Novel mutations of the tetratricopeptide repeat domain 7a gene and phenotype/genotype comparison. Front Immunol 2017; 8: 1066.
[http://dx.doi.org/10.3389/fimmu.2017.01066] [PMID: 28936210]
[101]
Blatch GL, Lässle M. The tetratricopeptide repeat: A structural motif mediating protein-protein interactions. BioEssays 1999; 21(11): 932-9.
[http://dx.doi.org/10.1002/(SICI)1521-1878(199911)21:11<932:AID-BIES5>3.0.CO;2-N] [PMID: 10517866]
[102]
Jardine S, Anderson S, Babcock S, Leung G, Pan J, Dhingani N. Drug screen identifies leflunomide for treatment of inflammatory bowel disease caused by TTC7A deficiency. Gastroenterology 2020; 158(4): 1000-15.
[http://dx.doi.org/10.1053/j.gastro.2019.11.019]
[103]
Breedveld FC, Dayer JM. Leflunomide: Mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis 2000; 59(11): 841-9.
[http://dx.doi.org/10.1136/ard.59.11.841] [PMID: 11053058]
[104]
Al-Bawardy B, Shivashankar R, Proctor DD. Novel and emerging therapies for inflammatory bowel disease. Front Pharmacol 2021; 12: 651415.
[http://dx.doi.org/10.3389/fphar.2021.651415]
[105]
De Winter BY, De Man JG. Interplay between inflammation, immune system and neuronal pathways: Effect on gastrointestinal motility. World J Gastroenterol 2010; 16(44): 5523-35.
[http://dx.doi.org/10.3748/wjg.v16.i44.5523] [PMID: 21105185]
[106]
Bumb A, Diederich N, Beyenburg S. Adding topiramate to valproate therapy may cause reversible hepatic failure. Epileptic Disord 2003; 5(3): 157-9.
[PMID: 14684351]
[107]
Stremmel W, Staffer S, Schneider MJ, et al. Genetic mouse models with intestinal-specific tight junction deletion resemble an ulcerative colitis phenotype. J Crohn’s Colitis 2017; 11(10): 1247-57.
[http://dx.doi.org/10.1093/ecco-jcc/jjx075] [PMID: 28575164]
[108]
Mumolo MG, Bertani L, Ceccarelli L, et al. From bench to bedside: Fecal calprotectin in inflammatory bowel diseases clinical setting. World J Gastroenterol 2018; 24(33): 3681-94.
[http://dx.doi.org/10.3748/wjg.v24.i33.3681] [PMID: 30197475]
[109]
Silva I, Mendes P, Guerra S, Pinto R, Mateus V. Anti-inflammatory effect of topiramate in a chronic model of TNBS-induced colitis. Int J Mol Sci 2022; 23(16): 9127.
[http://dx.doi.org/10.3390/ijms23169127] [PMID: 36012393]
[110]
Meng Y, Ma N, Lyu H, et al. Recent pharmacological advances in the repurposing of artemisinin drugs. Med Res Rev 2021; 41(6): 3156-81.
[http://dx.doi.org/10.1002/med.21837] [PMID: 34148245]
[111]
Chen YX, Zhang XQ, Yu CG, et al. Artesunate exerts protective effects against ulcerative colitis via suppressing Toll like receptor 4 and its downstream nuclear factor -κB signaling pathways. Mol Med Rep 2019; 20(2): 1321-32.
[http://dx.doi.org/10.3892/mmr.2019.10345] [PMID: 31173225]
[112]
Yan YX, Shao MJ, Qi Q, Xu YS, Yang XQ, Zhu FH. Artemisinin analogue SM934 ameliorates DSS-induced mouse ulcerative colitis via suppressing neutrophils and macrophages. Acta Pharmacol Sin 2018; 39(10): 1633-44.
[http://dx.doi.org/10.1038/aps.2017.185]
[113]
Ge X, Chen Z, Xu Z, Lv F, Zhang K, Yang Y. The effects of dihydroartemisinin on inflammatory bowel disease-related bone loss in a rat model. Exp Biol Med 2018; 243(8): 715-24.
[http://dx.doi.org/10.1177/1535370218769420] [PMID: 29763384]
[114]
Si CY, Ya JW, Yu JL. Dihydroartemisinin regulates the th/treg balance by inducing activated CD4+ T cell apoptosis via heme oxygenase-1 induction in mouse models of inflammatory bowel disease. Molecules 2019; 24(13): 2475.
[115]
Horrobin DF, Manku MS, Karmazyn M, Ally AI, Morgan RO, Karmali RA. Quinacrine is a prostaglandin antagonist. Biochem Biophys Res Commun 1977; 76: 1188-93.
[116]
Kara M, Yumrutas O, Atilgan R, Baspinar M, Sapmaz E, Kuloglu T. Expression changes of antioxidant, apoptotic, anti-apoptotic genes and miR-15b-34a-21-98 in over tissue by using erythromycin, quinacrine and tetracycline in non-surgical sterilization. Mol Biol Rep 2014; 41(12): 8093-8.
[http://dx.doi.org/10.1007/s11033-014-3707-3] [PMID: 25195052]
[117]
Ehsanian R, Van Waes C, Feller SM. Beyond DNA binding - a review of the potential mechanisms mediating quinacrine’s therapeutic activities in parasitic infections, inflammation, and cancers. Cell Commun Signal 2011; 9(1): 13.
[http://dx.doi.org/10.1186/1478-811X-9-13] [PMID: 21569639]
[118]
Zeitz J, Mullhaupt B, Fruehauf H, Rogler G, Vavricka SR. Hepatic failure due to hepatitis B reactivation in a patient with ulcerative colitis treated with prednisone. Hepatology 2009; 50(2): 653-4.
[http://dx.doi.org/10.1002/hep.23035] [PMID: 19575458]
[119]
Mohapatra P, Preet R, Das D, et al. Quinacrine-mediated autophagy and apoptosis in colon cancer cells is through a p53-and p21-dependent mechanism. Oncol Res Featur Preclin Clin Cancer Ther 2012; 20: 81-91.
[120]
Bai L, Scott MKD, Steinberg E, et al. Computational drug repositioning of atorvastatin for ulcerative colitis. J Am Med Inform Assoc 2021; 28(11): 2325-35.
[http://dx.doi.org/10.1093/jamia/ocab165] [PMID: 34529084]
[121]
Dhamija P, Hota D, Kochhar R, Sachdev A, Chakrabarti A. Randomized clinical trial: Atorvastatin versus placebo in patients with acute exacerbation of mild to moderate ulcerative colitis. Indian J Gastroenterol 2014; 33(2): 151-6.
[http://dx.doi.org/10.1007/s12664-013-0420-4] [PMID: 24222372]
[122]
Grip O, Janciauskiene S. Atorvastatin reduces plasma levels of chemokine (CXCL10) in patients with Crohn’s disease. PLoS One 2009; 4(5): e5263.
[http://dx.doi.org/10.1371/journal.pone.0005263] [PMID: 19421322]
[123]
Ruemmele FM, Seidman EG, Lentze MJ. Regulation of intestinal epithelial cell apoptosis and the pathogenesis of inflammatory bowel disorders. J Pediatr Gastroenterol Nutr 2002; 34(3): 254-60.
[http://dx.doi.org/10.1097/00005176-200203000-00005] [PMID: 11964947]
[124]
McCarey DW, McInnes IB, Madhok R, et al. Trial of atorvastatin in rheumatoid arthritis (TARA): Double-blind, randomised placebo-controlled trial. Lancet 2004; 363(9426): 2015-21.
[http://dx.doi.org/10.1016/S0140-6736(04)16449-0] [PMID: 15207950]
[125]
Dhaneshwar SS, Sharma M, Vadnerkar G. Co-drugs of aminosalicylates and nutraceutical amino sugar for ulcerative colitis. J Drug Deliv Sci Technol 2011; 21(6): 527-33.
[http://dx.doi.org/10.1016/S1773-2247(11)50085-1]
[126]
Li Y, Chen L, Liu Y, Zhang Y, Liang Y, Mei Y. Anti-inflammatory effects in a mouse osteoarthritis model of a mixture of glucosamine and chitooligosaccharides produced by bi-enzyme single-step hydrolysis. Sci Rep 2018; 8(1): 5624.
[http://dx.doi.org/10.1038/s41598-018-24050-6] [PMID: 29618773]
[127]
Roy S, Dhaneshwar S, Mahmood T, Kumar S, Saxena SK. Pre-clinical investigation of protective effect of nutraceutical D-glucosamine on TNBS-induced colitis. Immunopharmacol Immunotoxicol 2022; 45(2): 172-84.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy