Terazosin Stimulates Pgk1 to Remedy Gastrointestinal Disorders

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.

Targeting phosphoglycerate kinase 1 with terazosin improves motor neuron phenotypes in multiple models of amyotrophic lateral sclerosis

“…This is consistent with a role for PGK1 in regulating oxidative stress pathways. 43

Figure 4 Terazosin protects against NaArO 2 -induced cell death, increases glycolysis and decreases mitochondrial respiration in mESC-MNs . (a) TDP-43 M337V mESC-MNs show a decreased survival in response to sodium arsenite (NaArO 2 ) stress compared to unstressed controls.

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“…29 Terazosin has even been shown to be therapeutic in non-neurodegenerative indications such as gastrointestinal disorders. 43 The work presented here therefore builds on this body of evidence showing that terazosin can protect against degeneration across multiple diseases, and may be particularly important in the context of hard-to-treat neurodegenerative disorders due to the fact that terazosin can cross the blood-brain barrier. 31 Terazosin is an attractive candidate for therapy development due to its known safety profile in adults.…”

Polyaspartic Acid-Stabilized CaCO3-Containing In Situ Hydrogel for Protection and Treatment of Gastric Ulcer

“…Recent studies have shown that targeting GSDMD-executed pyroptosis effectively decreased the damage to gastric tissue. 8,42 Additionally, our animal and cell experiments have also demonstrated that Cur/SA/PC and Cur could regulate the NLRP3-mediated pyroptosis. These findings demonstrated that Cur/SA/PC could alleviate gastric injury by downregulating the NLRP3-mediated pyroptosis signaling pathway.…”

Nigakinone alleviates DSS‐induced experimental colitis via regulating bile acid profile and FXR/NLRP3 signaling pathways

“…As far as we know, the current study is the first to report the mechanism of nigakinone in UC treatment relating to BA profile regulation and anti‐inflammation via the activation of FXR. In our previous study, we showed that the mechanisms of nigakinone in colitis treatment might be related to anti‐inflammation and the regulation of BA metabolism according to non‐target metabolomics technology (Liu, Zhao, et al, 2021). Results of the present study have demonstrated that nigakinone treatment could substantially alleviate disease performance in DSS‐induced rats, such as body weight loss, diarrhea, hematochezia, secretion of MPO and iNOS, and colon tissue injury.…”