GNPS - Maytenus_woosonii_data_inmuno_paper
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Exploris 120
ORGANISM(S): Maytenus Woodsonii (ncbitaxon:1081529)
SUBMITTER: 
Giselle Tamayo-Castillo
PROVIDER: MSV000095590 | GNPS | Tue Aug 13 06:31:00 BST 2024
REPOSITORIES: GNPS
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Project description:Background: Dopamine has intrinsic receptor-independent anti-inflammatory properties when used at high concentrations. Since cellular uptake of N-octanoyl dopamine (NOD) is far better than of dopamine, NOD might display anti-inflammatory effects already at relative low concentrations. The present study was conducted to assess the anti-inflammatory potential of NOD and to elucidate how this was mediated. Methods: Human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-α in the presence of various NOD concentrations. Affymetrix gene expression profiling (GEP), Western blotting, adhesion of peripheral blood mononuclear cells (PBMC) to endothelial cells and NFκB activation was studied. Compounds that were structurally related to NOD were used to address the molecular entities within NOD that were required for its anti-inflammatory properties. Results: GEP revealed that NOD down-regulates a wide range of pro-inflammatory mediators. Down-regulation of adhesion molecules was confirmed at the protein level and resulted in a decreased adhesion of PBMC to endothelial cells under static and flow conditions. NOD inhibited NFκB independently of IκBα degradation. Inhibition was associated with an overall decrease in p65 expression and a significant decrease in p65 phosphorylation at Ser276. De novo protein synthesis was not required for inhibition and was not mediated via HO-1. Redox activity and hydrophobicity of NOD seemed to be important entities for its anti-inflammatory properties. Conclusion: Our data demonstrate that NOD has potent anti-inflammatory effects through its action on NFκB. Unlike dopamine, NOD has no adverse effects on blood pressure, making it a promising candidate drug to reduce excessive inflammation occurring under various pathological conditions. A total of 6 different HUVEC lines were used, n=3 for each group (TNF or TNF+ NOD).
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Project description:This study centered on detecting potentially anti-inflammatory active constituents in ethanolic extracts of Chinese Lonicera species by taking an UHPLC-HRMS-based metabolite profiling approach. Extracts from eight different Lonicera species were subjected to both UHPLC-HRMS analysis and to pharmacological testing in three different cellular inflammation-related assays. Compounds exhibiting high correlations in orthogonal projections to latent structures discriminant analysis (OPLS-DA) of pharmacological and MS data served as potentially activity-related candidates. Of these candidates, 65 were tentatively or unambiguously annotated. 7-Hydroxy-5,3',4',5'-tetramethoxyflavone and three bioflavonoids, as well as three C<sub>32</sub>- and one C<sub>34</sub>-acetylated polyhydroxy fatty acid, were isolated from <i>Lonicera hypoglauca</i> leaves for the first time, and their structures were fully or partially elucidated. Of the potentially active candidate compounds, 15 were subsequently subjected to pharmacological testing. Their activities could be experimentally verified in part, emphasizing the relevance of Lonicera species as a source of anti-inflammatory active constituents. However, some compounds also impaired the cell viability. Overall, the approach was found useful to narrow down the number of potentially bioactive constituents in the complex extracts investigated. In the future, the application of more refined concepts, such as extract prefractionation combined with bio-chemometrics, may help to further enhance the reliability of candidate selection.
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