Abstract
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.
Highlights
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
These levels were dramatically enhanced by 44 and 121% after Lop+Urd co-treatment, as compared with the Lop+Vehicle treated group (Figure 2). These results indicate that Urd treatment symptomatically improves chronic constipation in Lop-induced Sprague Dawley (SD) rats, without any changes in the feeding behavior
ER stress is considered as an attractive target for therapeutic discovery, since ER stress-induced cellular dysfunction and cell death is commonly detected in numerous diseases including neurodegenerative diseases, ophthalmology disorders, inflammation, viral infection, constipation, cancer, metabolic diseases and atherosclerosis [11]
Summary
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. The degradation of ER functions results in an ER stress response, which includes various molecular mechanisms such as attenuation of protein synthesis, induction of ER chaperone genes, increased ER-associated degradation (ERAD), and induction of apoptosis to safely dispose cells injured by ER stress [3] These processes are accompanied by accumulation of unfolded or misfolded proteins, leading to the activation of the unfolded protein response (UPR) [3]. The alterations of key indicators associated with ER stress significantly increased in the Lop-induced constipation SD rats compared with that of No treated group These levels were restored in the Lop+AEtLP treated group, the decrease rate was varied [7]. These results provide the first evidence that the laxative effects of Urd improve the ER stress induced during Lop treatment
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