Ginger Constituent 6-Shogaol Inhibits Inflammation- and Angiogenesis-Related Cell Functions in Primary Human Endothelial Cells
Rhizomes from Zingiber officinale Roscoe are traditionally used for the treatment of a plethora of pathophysiological conditions such as diarrhea, nausea, or rheumatoid arthritis. While 6-gingerol is the pungent principle in fresh ginger, in dried rhizomes, 6-gingerol is dehydrated to 6-shogaol. 6-S...
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| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.844767/full |
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| author | Iris Bischoff-Kont Tobias Primke Lea S. Niebergall Thomas Zech Robert Fürst Robert Fürst |
| author_facet | Iris Bischoff-Kont Tobias Primke Lea S. Niebergall Thomas Zech Robert Fürst Robert Fürst |
| author_sort | Iris Bischoff-Kont |
| collection | DOAJ |
| description | Rhizomes from Zingiber officinale Roscoe are traditionally used for the treatment of a plethora of pathophysiological conditions such as diarrhea, nausea, or rheumatoid arthritis. While 6-gingerol is the pungent principle in fresh ginger, in dried rhizomes, 6-gingerol is dehydrated to 6-shogaol. 6-Shogaol has been demonstrated to exhibit anticancer, antioxidative, and anti-inflammatory actions more effectively than 6-gingerol due to the presence of an electrophilic Michael acceptor moiety. In vitro, 6-shogaol exhibits anti-inflammatory actions in a variety of cell types, including leukocytes. Our study focused on the effects of 6-shogaol on activated endothelial cells. We found that 6-shogaol significantly reduced the adhesion of leukocytes onto lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs), resulting in a significantly reduced transmigration of THP-1 cells through an endothelial cell monolayer. Analyzing the mediators of endothelial cell–leukocyte interactions, we found that 30 µM of 6-shogaol blocked the LPS-triggered mRNA and protein expression of cell adhesion molecules. In concert with this, our study demonstrates that the LPS-induced nuclear factor κB (NFκB) promoter activity was significantly reduced upon treatment with 6-shogaol. Interestingly, the nuclear translocation of p65 was slightly decreased, and protein levels of the LPS receptor Toll-like receptor 4 remained unimpaired. Analyzing the impact of 6-shogaol on angiogenesis-related cell functions in vitro, we found that 6-shogaol attenuated the proliferation as well as the directed and undirected migration of HUVECs. Of note, 6-shogaol also strongly reduced the chemotactic migration of endothelial cells in the direction of a serum gradient. Moreover, 30 µM of 6-shogaol blocked the formation of vascular endothelial growth factor (VEGF)-induced endothelial sprouts from HUVEC spheroids and from murine aortic rings. Importantly, this study shows for the first time that 6-shogaol exhibits a vascular-disruptive impact on angiogenic sprouts from murine aortae. Our study demonstrates that the main bioactive ingredient in dried ginger, 6-shogaol, exhibits beneficial characteristics as an inhibitor of inflammation- and angiogenesis-related processes in vascular endothelial cells. |
| first_indexed | 2024-12-13T10:14:09Z |
| format | Article |
| id | doaj.art-7a92feef1e054169b43bbc30ae1797f2 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T10:14:09Z |
| publishDate | 2022-02-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-7a92feef1e054169b43bbc30ae1797f22022-12-21T23:51:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-02-011310.3389/fphar.2022.844767844767Ginger Constituent 6-Shogaol Inhibits Inflammation- and Angiogenesis-Related Cell Functions in Primary Human Endothelial CellsIris Bischoff-Kont0Tobias Primke1Lea S. Niebergall2Thomas Zech3Robert Fürst4Robert Fürst5Institute of Pharmaceutical Biology, Goethe University Frankfurt, Frankfurt, GermanyInstitute of Pharmaceutical Biology, Goethe University Frankfurt, Frankfurt, GermanyInstitute of Pharmaceutical Biology, Goethe University Frankfurt, Frankfurt, GermanyInstitute of Pharmaceutical Biology, Goethe University Frankfurt, Frankfurt, GermanyInstitute of Pharmaceutical Biology, Goethe University Frankfurt, Frankfurt, GermanyLOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG), Frankfurt, GermanyRhizomes from Zingiber officinale Roscoe are traditionally used for the treatment of a plethora of pathophysiological conditions such as diarrhea, nausea, or rheumatoid arthritis. While 6-gingerol is the pungent principle in fresh ginger, in dried rhizomes, 6-gingerol is dehydrated to 6-shogaol. 6-Shogaol has been demonstrated to exhibit anticancer, antioxidative, and anti-inflammatory actions more effectively than 6-gingerol due to the presence of an electrophilic Michael acceptor moiety. In vitro, 6-shogaol exhibits anti-inflammatory actions in a variety of cell types, including leukocytes. Our study focused on the effects of 6-shogaol on activated endothelial cells. We found that 6-shogaol significantly reduced the adhesion of leukocytes onto lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs), resulting in a significantly reduced transmigration of THP-1 cells through an endothelial cell monolayer. Analyzing the mediators of endothelial cell–leukocyte interactions, we found that 30 µM of 6-shogaol blocked the LPS-triggered mRNA and protein expression of cell adhesion molecules. In concert with this, our study demonstrates that the LPS-induced nuclear factor κB (NFκB) promoter activity was significantly reduced upon treatment with 6-shogaol. Interestingly, the nuclear translocation of p65 was slightly decreased, and protein levels of the LPS receptor Toll-like receptor 4 remained unimpaired. Analyzing the impact of 6-shogaol on angiogenesis-related cell functions in vitro, we found that 6-shogaol attenuated the proliferation as well as the directed and undirected migration of HUVECs. Of note, 6-shogaol also strongly reduced the chemotactic migration of endothelial cells in the direction of a serum gradient. Moreover, 30 µM of 6-shogaol blocked the formation of vascular endothelial growth factor (VEGF)-induced endothelial sprouts from HUVEC spheroids and from murine aortic rings. Importantly, this study shows for the first time that 6-shogaol exhibits a vascular-disruptive impact on angiogenic sprouts from murine aortae. Our study demonstrates that the main bioactive ingredient in dried ginger, 6-shogaol, exhibits beneficial characteristics as an inhibitor of inflammation- and angiogenesis-related processes in vascular endothelial cells.https://www.frontiersin.org/articles/10.3389/fphar.2022.844767/fullZingiber officinale Roscoe6-shogaolendothelial cellsinflammationangiogenesis-related cell functions |
| spellingShingle | Iris Bischoff-Kont Tobias Primke Lea S. Niebergall Thomas Zech Robert Fürst Robert Fürst Ginger Constituent 6-Shogaol Inhibits Inflammation- and Angiogenesis-Related Cell Functions in Primary Human Endothelial Cells Frontiers in Pharmacology Zingiber officinale Roscoe 6-shogaol endothelial cells inflammation angiogenesis-related cell functions |
| title | Ginger Constituent 6-Shogaol Inhibits Inflammation- and Angiogenesis-Related Cell Functions in Primary Human Endothelial Cells |
| title_full | Ginger Constituent 6-Shogaol Inhibits Inflammation- and Angiogenesis-Related Cell Functions in Primary Human Endothelial Cells |
| title_fullStr | Ginger Constituent 6-Shogaol Inhibits Inflammation- and Angiogenesis-Related Cell Functions in Primary Human Endothelial Cells |
| title_full_unstemmed | Ginger Constituent 6-Shogaol Inhibits Inflammation- and Angiogenesis-Related Cell Functions in Primary Human Endothelial Cells |
| title_short | Ginger Constituent 6-Shogaol Inhibits Inflammation- and Angiogenesis-Related Cell Functions in Primary Human Endothelial Cells |
| title_sort | ginger constituent 6 shogaol inhibits inflammation and angiogenesis related cell functions in primary human endothelial cells |
| topic | Zingiber officinale Roscoe 6-shogaol endothelial cells inflammation angiogenesis-related cell functions |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.844767/full |
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