Saw Palmetto Extract Enhances Erectile Responses by Inhibition of Phosphodiesterase 5 Activity and Increase in Inducible Nitric Oxide Synthase Messenger Ribonucleic Acid Expression in Rat and Rabbit Corpus Cavernosum

SummaryProteolytically active forms of thrombin (α- and γ-thrombin) and thrombin receptor peptides inhibited the release of nitrite, a stable endproduct of nitric oxide, evoked by interleukin-1 β(IL-1 β) in cultured vascular smooth muscle cells while proteolytically inactive forms [D-Phe-Pro-Arg chloromethyl ketone-α-thrombin (PPACK-α- thrombin) and diisopropylphosphoryl-α-thrombin (DIP-α-thrombin)] had either no or only minimal inhibitory effects. Under bioassay conditions, perfusates from columns containing IL-1 β-activated vascular smooth muscle cells or cells treated with IL-1βplus PPACK-α-thrombin relaxed detector blood vessels. These relaxations were abolished by the inhibitor of nitric oxide synthesis, NG-nitro-L arginine. No relaxations were obtained with untreated cells or IL-1 β-treated cells in the presence of α-thrombin. The expression of inducible nitric oxide synthase mRNA and protein in vascular smooth muscle cells by IL-1 β was impaired by α-thrombin. These results demonstrate that thrombin regulates the expression of the inducible nitric oxide synthase at a transcriptional level via the proteolytic activation of the thrombin receptor in vascular smooth muscle cells

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Faculty Opinions recommendation of Reversal of inducible nitric oxide synthase uncoupling unmasks tolerance to ischemia/reperfusion injury in the diabetic rat heart.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.8515956.8992054 ◽

2011 ◽

Author(s):

Michael Irwin ◽

Zhengyuan Xia

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Reperfusion Injury ◽

Inducible Nitric Oxide Synthase ◽

Rat Heart ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Diabetic Rat ◽

Oxide Synthase ◽

Inducible Nitric Oxide

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Search for Potential Inducible Nitric Oxide Synthase Inhibitors with Favorable ADMET Profiles for the Therapy of Helicobacter pylori Infections

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666191112105650 ◽

2020 ◽

Vol 19 (30) ◽

pp. 2795-2804 ◽

Cited By ~ 2

Author(s):

Ricardo Pereira Rodrigues ◽

Juliana Santa Ardisson ◽

Rita de Cássia Ribeiro Gonçalves ◽

Tiago Branquinho Oliveira ◽

Vinicius Barreto da Silva ◽

...

Keyword(s):

Nitric Oxide ◽

Helicobacter Pylori ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Crucial Role ◽

Chemical Space ◽

Target Selection ◽

Oxide Synthase ◽

Inos Inhibition ◽

Inducible Nitric Oxide

Background: Helicobacter pylori is a gram-negative bacterium related to chronic gastritis, peptic ulcer and gastric carcinoma. During its infection process, promotes excessive inflammatory response, increasing the release of reactive species and inducing the production of pro-inflammatory mediators. Inducible Nitric Oxide Synthase (iNOS) plays a crucial role in the gastric carcinogenesis process and a key mediator of inflammation and host defense systems, which is expressed in macrophages induced by inflammatory stimuli. In chronic diseases such as Helicobacter pylori infections, the overproduction of NO due to the prolonged induction of iNOS is of major concern. Objective: In this sense, the search for potential iNOS inhibitors is a valuable strategy in the overall process of Helicobacter pylori pathogeny. Method: In silico techniques were applied in the search of interesting compounds against Inducible Nitric Oxide Synthase enzyme in a chemical space of natural products and derivatives from the Analyticon Discovery databases. Results: The five compounds with the best iNOS inhibition profile were selected for activity and toxicity predictions. Compound 9 (CAS 88198-99-6) displayed significant potential for iNOS inhibition, forming hydrogen bonds with residues from the active site and an ionic interaction with heme. This compound also displayed good bioavailability and absence of toxicity/or from its probable metabolites. Conclusion: The top-ranked compounds from the virtual screening workflow show promising results regarding the iNOS inhibition profile. The results evidenced the importance of the ionic bonding during docking selection, playing a crucial role in binding and positioning during ligand-target selection for iNOS.

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