SAHA Alleviates Diarrhea-Predominant Irritable Bowel Syndrome Through Regulation of the p-STAT3/SERT/5-HT Signaling Pathway

References

• Enck P, Aziz Q, Barbara G, et al. Irritable bowel syndrome. Nat Rev Dis Primers. 2016;2:16014. doi:10.1038/nrdp.2016.14
   PubMed Web of Science ®Google Scholar
• Sultan S, Malhotra A. Irritable bowel syndrome. Ann Intern Med. 2017;166(11):ITC81–ITC96. doi:10.7326/AITC201706060
   PubMed Web of Science ®Google Scholar
• Holtmann GJ, Ford AC, Talley NJ. Pathophysiology of irritable bowel syndrome. Lancet Gastroenterol Hepatol. 2016;1(2):133–146. doi:10.1016/S2468-1253(16)30023-1
   PubMed Web of Science ®Google Scholar
• Ford AC, Lacy BE, Talley NJ. Irritable bowel syndrome. N Engl J Med. 2017;376(26):2566–2578. doi:10.1056/NEJMra1607547
   PubMed Web of Science ®Google Scholar
• Botschuijver S, Roeselers G, Levin E, et al. Intestinal fungal dysbiosis is associated with visceral hypersensitivity in patients with irritable bowel syndrome and rats. Gastroenterology. 2017;153(4):1026–1039. doi:10.1053/j.gastro.2017.06.004
   PubMed Web of Science ®Google Scholar
• Xu XJ, Zhang YL, Liu L, Pan L, Yao SK. Increased expression of nerve growth factor correlates with visceral hypersensitivity and impaired gut barrier function in diarrhoea-predominant irritable bowel syndrome: a preliminary explorative study. Aliment Pharmacol Ther. 2017;45(1):100–114. doi:10.1111/apt.13848
   PubMed Web of Science ®Google Scholar
• Gunn D, Garsed K, Lam C, et al. Abnormalities of mucosal serotonin metabolism and 5-HT3 receptor subunit 3C polymorphism in irritable bowel syndrome with diarrhoea predict responsiveness to ondansetron. Aliment Pharmacol Ther. 2019;50(5):538–546. doi:10.1111/apt.15420
   PubMed Web of Science ®Google Scholar
• Camilleri M. Intestinal secretory mechanisms in irritable bowel syndrome-diarrhea. Clin Gastroenterol Hepatol. 2015;13(6):1051–1057;quiz e1061–e1052. doi:10.1016/j.cgh.2014.07.020
   Web of Science ®Google Scholar
• Camilleri M. Management options for irritable bowel syndrome. Mayo Clin Proc. 2018;93(12):1858–1872. doi:10.1016/j.mayocp.2018.04.032
   PubMed Web of Science ®Google Scholar
• Qiu X, Xiao X, Li N, Li Y. Histone deacetylases inhibitors (HDACis) as novel therapeutic application in various clinical diseases. Prog Neuropsychopharmacol Biol Psychiatry. 2017;72:60–72. doi:10.1016/j.pnpbp.2016.09.002
   PubMed Web of Science ®Google Scholar
• Moloney RD, Stilling RM, Dinan TG, Cryan JF. Early-life stress-induced visceral hypersensitivity and anxiety behavior is reversed by histone deacetylase inhibition. Neurogastroenterol Motil. 2015;27(12):1831–1836. doi:10.1111/nmo.12675
   PubMed Web of Science ®Google Scholar
• Li B, Rui J, Ding X, Chen Y, Yang X. Deciphering the multicomponent synergy mechanisms of SiNiSan prescription on irritable bowel syndrome using a bioinformatics/network topology based strategy. Phytomedicine. 2019;63:152982. doi:10.1016/j.phymed.2019.152982
   PubMed Web of Science ®Google Scholar
• Kong E, Sucic S, Monje FJ, et al. STAT3 controls IL6-dependent regulation of serotonin transporter function and depression-like behavior. Sci Rep. 2015;5:9009. doi:10.1038/srep09009
   PubMed Web of Science ®Google Scholar
• Foley S, Garsed K, Singh G, et al. Impaired uptake of serotonin by platelets from patients with irritable bowel syndrome correlates with duodenal immune activation. Gastroenterology. 2011;140(5):1434–1443 e1431. doi:10.1053/j.gastro.2011.01.052
   PubMed Web of Science ®Google Scholar
• Yang H, Lan P, Hou Z, et al. Histone deacetylase inhibitor SAHA epigenetically regulates miR-17-92 cluster and MCM7 to upregulate MICA expression in hepatoma. Br J Cancer. 2015;112(1):112–121. doi:10.1038/bjc.2014.547
   PubMed Web of Science ®Google Scholar
• Zhang M, Wei W, Peng C, et al. Discovery of novel pyrazolopyrimidine derivatives as potent mTOR/HDAC bi-functional inhibitors via pharmacophore-merging strategy. Bioorg Med Chem Lett. 2021;49:128286. doi:10.1016/j.bmcl.2021.128286
   PubMed Web of Science ®Google Scholar
• Cao D-Y, Bai G, Ji Y, Karpowicz JM, Traub RJ. EXPRESS: histone hyperacetylation modulates spinal type II metabotropic glutamate receptor alleviating stress-induced visceral hypersensitivity in female rats. Mol Pain. 2016;12:174480691666072. doi:10.1177/1744806916660722
   Web of Science ®Google Scholar
• El-Ayache N, Galligan JJ. 5-HT3 receptor signaling in serotonin transporter-knockout rats: a female sex-specific animal model of visceral hypersensitivity. Am J Physiol Gastrointest Liver Physiol. 2019;316(1):G132–G143. doi:10.1152/ajpgi.00131.2018
   PubMed Web of Science ®Google Scholar
• Park JH, Rhee PL, Kim HS, et al. Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea predominant irritable bowel syndrome. J Gastroenterol Hepatol. 2006;21(1 Pt 1):71–78. doi:10.1111/j.1440-1746.2005.04143.x
   PubMed Web of Science ®Google Scholar
• Zhao JM, Lu JH, Yin XJ, et al. Comparison of electroacupuncture and moxibustion on brain-gut function in patients with diarrhea-predominant irritable bowel syndrome: a randomized controlled trial. Chin J Integr Med. 2015;21(11):855–865. doi:10.1007/s11655-015-2049-x
   PubMed Web of Science ®Google Scholar
• Zhang Y, Zhang H, Zhang W, Zhang Y, Wang W, Nie L. LncRNA XIST modulates 5-hydroxytrytophan-induced visceral hypersensitivity by epigenetic silencing of the SERT gene in mice with diarrhea-predominant IBS. Cell Signal. 2020;73:109674. doi:10.1016/j.cellsig.2020.109674
   PubMed Web of Science ®Google Scholar
• Zhuang X, Tian Z, Li L, Zeng Z, Chen M, Xiong L. Fecal microbiota alterations associated with diarrhea-predominant irritable bowel syndrome. Front Microbiol. 2018;9:1600. doi:10.3389/fmicb.2018.01600
   PubMed Web of Science ®Google Scholar
• Fellows R, Varga-Weisz P. Chromatin dynamics and histone modifications in intestinal microbiota-host crosstalk. Mol Metab. 2020;38:100925. doi:10.1016/j.molmet.2019.12.005
   PubMed Web of Science ®Google Scholar
• Chitkara DK, van Tilburg MA, Blois-Martin N, Whitehead WE. Early life risk factors that contribute to irritable bowel syndrome in adults: a systematic review. Am J Gastroenterol. 2008;103(3):765–774;quiz 775. doi:10.1111/j.1572-0241.2007.01722.x
   Web of Science ®Google Scholar
• Bednarska O, Walter SA, Casado-Bedmar M, et al. Vasoactive intestinal polypeptide and mast cells regulate increased passage of colonic bacteria in patients with irritable bowel syndrome. Gastroenterology. 2017;153(4):948–960 e943. doi:10.1053/j.gastro.2017.06.051
   PubMed Web of Science ®Google Scholar
• Grabauskas G, Wu X, Gao J, Li JY, Turgeon DK, Owyang C. Prostaglandin E2, produced by mast cells in colon tissues from patients with irritable bowel syndrome, contributes to visceral hypersensitivity in mice. Gastroenterology. 2020;158(8):2195–2207 e2196. doi:10.1053/j.gastro.2020.02.022
   PubMed Web of Science ®Google Scholar
• Coates MD, Tekin I, Vrana KE, Mawe GM. Review article: the many potential roles of intestinal serotonin (5-hydroxytryptamine, 5-HT) signalling in inflammatory bowel disease. Aliment Pharmacol Ther. 2017;46(6):569–580. doi:10.1111/apt.14226
   PubMed Web of Science ®Google Scholar
• Asagarasu A, Matsui T, Hayashi H, et al. Discovery of a novel 5-HT(3) antagonist/5-HT(1A) agonist 3-amino-5,6,7,8-tetrahydro-2-{4-[4-(quinolin-2-yl)piperazin-1-yl]butyl}quinazolin −4(3H)-one (TZB-30878) as an orally bioavailable agent for irritable bowel syndrome. J Med Chem. 2010;53(21):7549–7563. doi:10.1021/jm1002292
   PubMed Web of Science ®Google Scholar
• Rebholz H, Friedman E, Castello J. Alterations of expression of the serotonin 5-HT4 receptor in brain disorders. Int J Mol Sci. 2018;19(11). doi:10.3390/ijms19113581
   Web of Science ®Google Scholar
• Chen MX, Chen Y, Fu R, Liu SY, Yang QQ, Shen TB. Activation of 5-HT and NR2B contributes to visceral hypersensitivity in irritable bowel syndrome in rats. Am J Transl Res. 2016;8(12):5580–5590.
   PubMed Web of Science ®Google Scholar
• Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004;126(7):1657–1664. doi:10.1053/j.gastro.2004.03.013
   PubMed Web of Science ®Google Scholar
• Camilleri M, Andrews CN, Bharucha AE, et al. Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome. Gastroenterology. 2007;132(1):17–25. doi:10.1053/j.gastro.2006.11.020
   PubMed Web of Science ®Google Scholar
• Buckley MM, O’Halloran KD, Rae MG, Dinan TG, O’Malley D. Modulation of enteric neurons by interleukin-6 and corticotropin-releasing factor contributes to visceral hypersensitivity and altered colonic motility in a rat model of irritable bowel syndrome. J Physiol. 2014;592(23):5235–5250. doi:10.1113/jphysiol.2014.279968
   PubMed Web of Science ®Google Scholar