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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Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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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. |
format | Article |
id | doaj-art-12291e8ff5c544b0a1237407896e86a4 |
institution | Kabale University |
issn | 1932-6203 |
language | English |
publishDate | 2025-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
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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