Abstract
Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them, the most frequent diseases are gastric ulcer (GU) and ulcerative colitis (UC). DSS-induced UC and ethanol-stimulated GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. Our results indicate that terazosin dramatically activates Pgk1, and upregulates glycose metabolism, evidenced by the enhanced ATP production and higher LDH enzymatic activity. Also, terazosin significantly enhances p-AKT expression and inhibits NF-κB p65 activation through abrogating the phosphorylation of IKBα, as well as lowers Caspase-1 and GSDMD expression. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Meanwhile, we also find terazosin ameliorates ethanol-induced gastric mucosal damage in mice. Collectively, as a clinical drug, terazosin should be translated into therapeutics for gastrointestinal disease soon.
Highlights
Gastric ulcer (GU) models resemble the pathophysiology of human gastrointestinal disease
The effect of terazosin on cell viability in Caco-2 cells was examined via MTT assay, and the results showed that treatment with terazosin (100 and 10 nM) for 24 h did not show any cytotoxicity (Figure 1A)
This paper mainly introduced the effects of terazosin in acute gastrointestinal diseases, including Gastric ulcer (GU) and Ulcerative colitis (UC)
Summary
GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Common symptoms include vomiting and nausea, abdominal discomfort, diarrhea, acid reflux, unintentional weight loss, fatigue, swallowing difficulty, fever, black and bloody stool, gastrointestinal bleeding, and intestinal obstruction [3]. The occurrence of UC is thought to be complex and multifactorial, maybe due to environmental, infectious, immunological, psychological, and genetic factors [6] Under unfavorable conditions these factors induce the release of pro-inflammatory mediators, such as reactive oxygen species, cytokines, and neutrophil infiltration, which are considered as markers in the pathogenesis of colitis [7,8]. The common clinical manifestations of ulcerative colitis mainly include abdominal pain, diarrhea, blood in the stool, fever, reduced appetite, and weight loss [9]. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
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