Elder (Sambucus nigra), identified by high-content screening, counteracts foam cell formation without promoting hepatic lipogenesis
Abstract Cholesterol deposition in intimal macrophages leads to foam cell formation and atherosclerosis. Reverse cholesterol transport (RCT), initiated by efflux of excess cholesterol from foam cells, counteracts atherosclerosis. However, targeting RCT by enhancing cholesterol efflux was so far acco...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-54108-7 |
| _version_ | 1827327875487891456 |
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| author | Stefanie Steinbauer Alice König Cathrina Neuhauser Bettina Schwarzinger Herbert Stangl Marcus Iken Julian Weghuber Clemens Röhrl |
| author_facet | Stefanie Steinbauer Alice König Cathrina Neuhauser Bettina Schwarzinger Herbert Stangl Marcus Iken Julian Weghuber Clemens Röhrl |
| author_sort | Stefanie Steinbauer |
| collection | DOAJ |
| description | Abstract Cholesterol deposition in intimal macrophages leads to foam cell formation and atherosclerosis. Reverse cholesterol transport (RCT), initiated by efflux of excess cholesterol from foam cells, counteracts atherosclerosis. However, targeting RCT by enhancing cholesterol efflux was so far accompanied by adverse hepatic lipogenesis. Here, we aimed to identify novel natural enhancers of macrophage cholesterol efflux suitable for the prevention of atherosclerosis. Plant extracts of an open-access library were screened for their capacity to increase cholesterol efflux in RAW264.7 macrophages trace-labeled with fluorescent BODIPY-cholesterol. Incremental functional validation of hits yielded two final extracts, elder (Sambucus nigra) and bitter orange (Citrus aurantium L.) that induced ATP binding cassette transporter A1 (ABCA1) expression and reduced cholesteryl ester accumulation in aggregated LDL-induced foam cells. Aqueous elder extracts were subsequently prepared in-house and both, flower and leaf extracts increased ABCA1 mRNA and protein expression in human THP-1 macrophages, while lipogenic gene expression in hepatocyte-derived cells was not induced. Chlorogenic acid isomers and the quercetin glycoside rutin were identified as the main polyphenols in elder extracts with putative biological action. In summary, elder flower and leaf extracts increase macrophage ABCA1 expression and reduce foam cell formation without adversely affecting hepatic lipogenesis. |
| first_indexed | 2024-03-07T15:08:45Z |
| format | Article |
| id | doaj.art-00bf50f0f31c46ada9dc0a8e8d00b5e6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:08:45Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-00bf50f0f31c46ada9dc0a8e8d00b5e62024-03-05T18:45:50ZengNature PortfolioScientific Reports2045-23222024-02-0114111210.1038/s41598-024-54108-7Elder (Sambucus nigra), identified by high-content screening, counteracts foam cell formation without promoting hepatic lipogenesisStefanie Steinbauer0Alice König1Cathrina Neuhauser2Bettina Schwarzinger3Herbert Stangl4Marcus Iken5Julian Weghuber6Clemens Röhrl7University of Applied Sciences Upper AustriaUniversity of Applied Sciences Upper AustriaAustrian Competence Center for Feed and Food Quality, Safety and InnovationUniversity of Applied Sciences Upper AustriaCenter for Pathobiochemistry and Genetics, Institute of Medical Chemistry, Medical University of ViennaPM International AGUniversity of Applied Sciences Upper AustriaUniversity of Applied Sciences Upper AustriaAbstract Cholesterol deposition in intimal macrophages leads to foam cell formation and atherosclerosis. Reverse cholesterol transport (RCT), initiated by efflux of excess cholesterol from foam cells, counteracts atherosclerosis. However, targeting RCT by enhancing cholesterol efflux was so far accompanied by adverse hepatic lipogenesis. Here, we aimed to identify novel natural enhancers of macrophage cholesterol efflux suitable for the prevention of atherosclerosis. Plant extracts of an open-access library were screened for their capacity to increase cholesterol efflux in RAW264.7 macrophages trace-labeled with fluorescent BODIPY-cholesterol. Incremental functional validation of hits yielded two final extracts, elder (Sambucus nigra) and bitter orange (Citrus aurantium L.) that induced ATP binding cassette transporter A1 (ABCA1) expression and reduced cholesteryl ester accumulation in aggregated LDL-induced foam cells. Aqueous elder extracts were subsequently prepared in-house and both, flower and leaf extracts increased ABCA1 mRNA and protein expression in human THP-1 macrophages, while lipogenic gene expression in hepatocyte-derived cells was not induced. Chlorogenic acid isomers and the quercetin glycoside rutin were identified as the main polyphenols in elder extracts with putative biological action. In summary, elder flower and leaf extracts increase macrophage ABCA1 expression and reduce foam cell formation without adversely affecting hepatic lipogenesis.https://doi.org/10.1038/s41598-024-54108-7 |
| spellingShingle | Stefanie Steinbauer Alice König Cathrina Neuhauser Bettina Schwarzinger Herbert Stangl Marcus Iken Julian Weghuber Clemens Röhrl Elder (Sambucus nigra), identified by high-content screening, counteracts foam cell formation without promoting hepatic lipogenesis Scientific Reports |
| title | Elder (Sambucus nigra), identified by high-content screening, counteracts foam cell formation without promoting hepatic lipogenesis |
| title_full | Elder (Sambucus nigra), identified by high-content screening, counteracts foam cell formation without promoting hepatic lipogenesis |
| title_fullStr | Elder (Sambucus nigra), identified by high-content screening, counteracts foam cell formation without promoting hepatic lipogenesis |
| title_full_unstemmed | Elder (Sambucus nigra), identified by high-content screening, counteracts foam cell formation without promoting hepatic lipogenesis |
| title_short | Elder (Sambucus nigra), identified by high-content screening, counteracts foam cell formation without promoting hepatic lipogenesis |
| title_sort | elder sambucus nigra identified by high content screening counteracts foam cell formation without promoting hepatic lipogenesis |
| url | https://doi.org/10.1038/s41598-024-54108-7 |
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