Nutraceutical COMP-4 confers protection against endothelial dysfunction through the eNOS/iNOS-NO-cGMP pathway.

The nutraceutical COMP-4 -consisting of L-citrulline, ginger extract, and herbal components Paullinia cupana and muira puama-has been shown previously to stimulate the production of nitric oxide (NO) in a variety of tissue types. We hypothesized that COMP-4 may have a protective, stimulatory effect...

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Main Authors: Monica G Ferrini, Andrea Abraham, Revecca Millán, Leslie Graciano, Sriram V Eleswarapu, Jacob Rajfer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0316798
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author Monica G Ferrini
Andrea Abraham
Revecca Millán
Leslie Graciano
Sriram V Eleswarapu
Jacob Rajfer
author_facet Monica G Ferrini
Andrea Abraham
Revecca Millán
Leslie Graciano
Sriram V Eleswarapu
Jacob Rajfer
author_sort Monica G Ferrini
collection DOAJ
description The nutraceutical COMP-4 -consisting of L-citrulline, ginger extract, and herbal components Paullinia cupana and muira puama-has been shown previously to stimulate the production of nitric oxide (NO) in a variety of tissue types. We hypothesized that COMP-4 may have a protective, stimulatory effect on the vascular endothelial cell. Human umbilical arterial endothelial cells were incubated for 24 hours with or without COMP-4 and, to replicate impairment of endothelial function, co-incubated with or without H2O2. NO intracellular content, nitrite formation and cGMP content in culture media, nitric oxide synthase (NOS) isoforms and mRNA content, pro-inflammatory cytokines, and PAI-1 expression and activity were measured. COMP-4 increased endothelial cell production of NO and cGMP and the expression of both endothelial NOS (eNOS) and inducible NOS (iNOS), in tandem with a reduction in cytokine expression and activity of PAI-1. Co-incubation of COMP-4 with H2O2 reversed detrimental effects of H2O2 on endothelial function, evidenced by improvement in NO availability and abrogation of the pro-inflammatory milieu. These results suggest that COMP-4 exerts a stimulatory effect on endothelial cell eNOS and iNOS to increase NO bioavailability, leading to a reduction in pro-inflammatory cytokines, particularly the prothrombotic PAI-1.
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spelling doaj-art-12291e8ff5c544b0a1237407896e86a42025-02-12T05:31:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01202e031679810.1371/journal.pone.0316798Nutraceutical COMP-4 confers protection against endothelial dysfunction through the eNOS/iNOS-NO-cGMP pathway.Monica G FerriniAndrea AbrahamRevecca MillánLeslie GracianoSriram V EleswarapuJacob RajferThe nutraceutical COMP-4 -consisting of L-citrulline, ginger extract, and herbal components Paullinia cupana and muira puama-has been shown previously to stimulate the production of nitric oxide (NO) in a variety of tissue types. We hypothesized that COMP-4 may have a protective, stimulatory effect on the vascular endothelial cell. Human umbilical arterial endothelial cells were incubated for 24 hours with or without COMP-4 and, to replicate impairment of endothelial function, co-incubated with or without H2O2. NO intracellular content, nitrite formation and cGMP content in culture media, nitric oxide synthase (NOS) isoforms and mRNA content, pro-inflammatory cytokines, and PAI-1 expression and activity were measured. COMP-4 increased endothelial cell production of NO and cGMP and the expression of both endothelial NOS (eNOS) and inducible NOS (iNOS), in tandem with a reduction in cytokine expression and activity of PAI-1. Co-incubation of COMP-4 with H2O2 reversed detrimental effects of H2O2 on endothelial function, evidenced by improvement in NO availability and abrogation of the pro-inflammatory milieu. These results suggest that COMP-4 exerts a stimulatory effect on endothelial cell eNOS and iNOS to increase NO bioavailability, leading to a reduction in pro-inflammatory cytokines, particularly the prothrombotic PAI-1.https://doi.org/10.1371/journal.pone.0316798
spellingShingle Monica G Ferrini
Andrea Abraham
Revecca Millán
Leslie Graciano
Sriram V Eleswarapu
Jacob Rajfer
Nutraceutical COMP-4 confers protection against endothelial dysfunction through the eNOS/iNOS-NO-cGMP pathway.
PLoS ONE
title Nutraceutical COMP-4 confers protection against endothelial dysfunction through the eNOS/iNOS-NO-cGMP pathway.
title_full Nutraceutical COMP-4 confers protection against endothelial dysfunction through the eNOS/iNOS-NO-cGMP pathway.
title_fullStr Nutraceutical COMP-4 confers protection against endothelial dysfunction through the eNOS/iNOS-NO-cGMP pathway.
title_full_unstemmed Nutraceutical COMP-4 confers protection against endothelial dysfunction through the eNOS/iNOS-NO-cGMP pathway.
title_short Nutraceutical COMP-4 confers protection against endothelial dysfunction through the eNOS/iNOS-NO-cGMP pathway.
title_sort nutraceutical comp 4 confers protection against endothelial dysfunction through the enos inos no cgmp pathway
url https://doi.org/10.1371/journal.pone.0316798
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