Skip to main content

Correlation between laxative effects of uridine and suppression of ER stress in loperamide induced constipated SD rats


A correlation between endoplasmic reticulum (ER) stress and laxative effects was first reported in a constipation model treated with an aqueous extract of Liriope platyphylla (AEtLP) roots. To investigate the correlation between the laxative effect of uridine (Urd) and ER stress response, alterations in the key parameters for ER stress were measured in loperamide (Lop) induced constipation Sprague Dawley (SD) rats treated with Urd. The efficacy of the laxative effect of Urd was notable on the symptoms of chronic constipation, including alteration of stool parameters and structure of the transverse colon, in Lop induced constipated SD rats. In the PERK/eIF2-ATF4 pathway of ER stress response, the levels of eukaryotic initiation factor 2 alpha (eIF2a) phosphorylation and DNA damage-inducible protein (GADD34) transcripts were significantly enhanced in the Lop+Vehicle treated group. However, the levels were restored in the Lop+Urd treated group, although few differences were detected in the decrease rate. Similar changes were observed for levels of inositol-requiring enzyme 1 beta (IRE1ß) phosphorylation and X-box binding protein 1 (XBP-1) transcript in the IRE1α/XBP pathway. Furthermore, the number of ER stress-induced apoptotic cells and Bax and Bcl-2 expression were recovered in the Lop+Urd treated group compared to the Lop+Vehicle treated group. The results of the present study therefore provide first evidence that the laxative effects of Urd may be tightly correlated with the recovery of ER stress response in constipation models.


  1. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell, 5th ed, Garland Science, New York, 2008; pp 723–748.

    Google Scholar 

  2. Schönthal AH. Endoplasmic reticulum stress: Its role in disease and novel prospects for therapy. Scientifica 2012; 2012: 857516.

  3. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 2007; 8(2): 519–529.

    Article  CAS  Google Scholar 

  4. Yoshida H. ER stress and disease. FEBS J 2007; 274(4): 630–658.

    Article  CAS  Google Scholar 

  5. Forman MS, Lee VM, Trojanowski JQ. ‘Unfolding’ pathways in neurodegenerative disease. Trends Neurosci 2003; 26(3): 407–410.

    Article  CAS  Google Scholar 

  6. Ozcan L, Tabas I. Role of endoplasmic reticulum stress in metabolic disease and other disorders. Annu Rev Med 2012; 63: 317–328.

    Article  CAS  Google Scholar 

  7. Kim JE, Go J, Sung JE, Lee HA, Seo EJ, Yun WB, Hwang DY. Laxative effects of Liriope platyphylla are tightly correlated with suppression of endoplasmic reticulum stress in loperamideinduced constipation of SD rats. Lab Anim Res 2016; 32(3): 16–23.

    Article  Google Scholar 

  8. Kim JE, Go J, Sung JE, Lee HA, Yun WB, Hong JT, Hwang DY. Uridine stimulate laxative effect in the loperamide-induced constipation of SD rats through regulation of the mAChRs signaling pathway and mucin secretion. BMC Gastroenterol 2017; 17(3): 21.

    Article  Google Scholar 

  9. Kim JE, Lee YJ, Kwak MH, Ko J, Hong JT, Hwang DY. Aqueous extracts of Liriope platyphylla induced significant laxative effects on loperamide-induced constipation of SD rats. BMC Complement Altern Med 2013; 13: 333.

    Article  Google Scholar 

  10. Scull CM, Tabas I. Mechanisms of ER stress-induced apoptosis in atherosclerosis. Arterioscler Thromb Vasc Biol 2011; 31(12): 2792–2797.

    Article  CAS  Google Scholar 

  11. Sano R, Reed JC. ER stress-induced cell death mechanisms. Biochim Biophys Acta 2013; 1833(12): 3460–3470.

    Article  Google Scholar 

  12. Doughty D. Structure and function of the gastrointestinal tract in infants and children. J Wound Ostomy Continence Nurs 2004; 31(3): 207–212.

    Article  Google Scholar 

  13. Shen L. Functional morphology of the gastrointestinal tract. Curr Top Microbiol Immunol 2009; 337: 1–35.

    CAS  PubMed  Google Scholar 

  14. Alves GA, Silva LR, Rosa EF, Aboulafia J, Freymüller-Haapalainen E, Souccar C, Nouailhetas VL. Intestine of dystrophic mice presents enhanced contractile resistance to stretching despite morphological impairment. Am J Physiol Gastrointest Liver Physiol 2014; 306(4): G191–199.

    Article  Google Scholar 

  15. Chan OT, Chiles L, Levy M, Zhai J, Yerian LM, Xu H, Xiao SY, Soffer EE, Conklin JL, Dhall D, Kahn ME, Balzer BL, Amin MB, Wang HL. Smoothelin expression in the gastrointestinal tract: implication in colonic inertia. Appl Immunohistochem Mol Morphol 2013; 21(3): 452–459.

    Article  Google Scholar 

  16. Tóth S, Jonecová Z, Varga J, Staško P, Kovavalcinová B, Maretta M, Veselá J. Mesenteric ischemia-reperfusion injury: specific impact on different cell populations within the jejunal wall in rats. Acta Histochem 2012; 114(4): 276–284.

    Article  Google Scholar 

  17. Karri S, Acosta-Martinez V, Coimbatore G. Effect of dihydrotestosterone on gastrointestinal tract of male Alzheimer’s disease transgenic mice. Indian J Exp Biol 2010; 48(3): 453–465.

    CAS  PubMed  Google Scholar 

  18. Cao W, Fiocchi C, Pricolo VE. Production of IL-1beta, hydrogen peroxide, and nitric oxide by colonic mucosa decreases sigmoid smooth muscle contractility in ulcerative colitis. Am J Physiol Cell Physiol 2005; 289(4): C1408–1416.

    Article  Google Scholar 

  19. Oakes SA, Lin SS, Bassik MC. The control of endoplasmic reticulum-initiated apoptosis by the BCL-2 family of proteins. Curr Mol Med 2006; 6(2): 99–109.

    Article  CAS  Google Scholar 

  20. Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 2001; 292(5517): 727–730.

    Article  CAS  Google Scholar 

  21. McCullough KD, Martindale JL, Klotz LO, Aw TY, Holbrook NJ. Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol Cell Biol 2001; 21: 1249–1259.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Dae Youn Hwang.

Rights and permissions

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, J.E., Song, B.R., Yun, W.B. et al. Correlation between laxative effects of uridine and suppression of ER stress in loperamide induced constipated SD rats. Lab Anim Res 33, 298–307 (2017).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: