Panduratin A Inhibits TNF Alpha-Stimulated Endothelial Cell Activation Through Suppressing the NF-κB Pathway
Upon exposure to inflammatory stimuli including TNF-α, endothelial cells are activated leading to the adhesion of monocytes to their surface. These events are involved in the pathophysiology of atherosclerosis. Since TNF-α activates the NF-κB pathway, which contributes to atherosclerosis, targeting...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/15/1/34 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832588974175027200 |
|---|---|
| author | Kriangkrai Kiatsoonthon Nitchakarn Phimthong Saranyapin Potikanond Nitwara Wikan Wutigri Nimlamool |
| author_facet | Kriangkrai Kiatsoonthon Nitchakarn Phimthong Saranyapin Potikanond Nitwara Wikan Wutigri Nimlamool |
| author_sort | Kriangkrai Kiatsoonthon |
| collection | DOAJ |
| description | Upon exposure to inflammatory stimuli including TNF-α, endothelial cells are activated leading to the adhesion of monocytes to their surface. These events are involved in the pathophysiology of atherosclerosis. Since TNF-α activates the NF-κB pathway, which contributes to atherosclerosis, targeting this signaling pathway may help prevent the risk of developing the disease. The current study elucidated the inhibitory effect of panduratin A (PA) on TNF-α-induced endothelial activation and monocyte adhesion. We discovered that PA reduced the level of pro-inflammatory cytokine IL-6 and chemokine MCP-1 in the media collected from endothelial cells stimulated with TNF-α. In addition, PA inhibited the expression of ICAM-1 and VCAM-1 on the surface of TNF-α-induced endothelial cells resulting in a decrease in the number of monocytes attached to endothelial cell surface. Mechanistically, PA prevented IκB degradation and specifically suppressed NF-κB phosphorylation and nuclear translocation in endothelial cells. However, PA had no inhibitory effect on the phosphorylation of AKT, ERK1/2, p38, and JNK. Taken together, PA blocked the production of cytokine and chemokine, adhesion molecules, and monocyte adhesion in response to TNF-α stimulation, in part, through NF-κB inhibition. Our study suggests that PA may possibly be effective in blocking the pathophysiology of atherosclerosis. |
| format | Article |
| id | doaj-art-5ee0acaef0394315ad49d78514542a57 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-5ee0acaef0394315ad49d78514542a572025-01-24T13:24:56ZengMDPI AGBiomolecules2218-273X2024-12-011513410.3390/biom15010034Panduratin A Inhibits TNF Alpha-Stimulated Endothelial Cell Activation Through Suppressing the NF-κB PathwayKriangkrai Kiatsoonthon0Nitchakarn Phimthong1Saranyapin Potikanond2Nitwara Wikan3Wutigri Nimlamool4Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandUpon exposure to inflammatory stimuli including TNF-α, endothelial cells are activated leading to the adhesion of monocytes to their surface. These events are involved in the pathophysiology of atherosclerosis. Since TNF-α activates the NF-κB pathway, which contributes to atherosclerosis, targeting this signaling pathway may help prevent the risk of developing the disease. The current study elucidated the inhibitory effect of panduratin A (PA) on TNF-α-induced endothelial activation and monocyte adhesion. We discovered that PA reduced the level of pro-inflammatory cytokine IL-6 and chemokine MCP-1 in the media collected from endothelial cells stimulated with TNF-α. In addition, PA inhibited the expression of ICAM-1 and VCAM-1 on the surface of TNF-α-induced endothelial cells resulting in a decrease in the number of monocytes attached to endothelial cell surface. Mechanistically, PA prevented IκB degradation and specifically suppressed NF-κB phosphorylation and nuclear translocation in endothelial cells. However, PA had no inhibitory effect on the phosphorylation of AKT, ERK1/2, p38, and JNK. Taken together, PA blocked the production of cytokine and chemokine, adhesion molecules, and monocyte adhesion in response to TNF-α stimulation, in part, through NF-κB inhibition. Our study suggests that PA may possibly be effective in blocking the pathophysiology of atherosclerosis.https://www.mdpi.com/2218-273X/15/1/34endothelial activationVCAM-1ICAM-1monocyte adhesionatherosclerosisTNF-alpha |
| spellingShingle | Kriangkrai Kiatsoonthon Nitchakarn Phimthong Saranyapin Potikanond Nitwara Wikan Wutigri Nimlamool Panduratin A Inhibits TNF Alpha-Stimulated Endothelial Cell Activation Through Suppressing the NF-κB Pathway Biomolecules endothelial activation VCAM-1 ICAM-1 monocyte adhesion atherosclerosis TNF-alpha |
| title | Panduratin A Inhibits TNF Alpha-Stimulated Endothelial Cell Activation Through Suppressing the NF-κB Pathway |
| title_full | Panduratin A Inhibits TNF Alpha-Stimulated Endothelial Cell Activation Through Suppressing the NF-κB Pathway |
| title_fullStr | Panduratin A Inhibits TNF Alpha-Stimulated Endothelial Cell Activation Through Suppressing the NF-κB Pathway |
| title_full_unstemmed | Panduratin A Inhibits TNF Alpha-Stimulated Endothelial Cell Activation Through Suppressing the NF-κB Pathway |
| title_short | Panduratin A Inhibits TNF Alpha-Stimulated Endothelial Cell Activation Through Suppressing the NF-κB Pathway |
| title_sort | panduratin a inhibits tnf alpha stimulated endothelial cell activation through suppressing the nf κb pathway |
| topic | endothelial activation VCAM-1 ICAM-1 monocyte adhesion atherosclerosis TNF-alpha |
| url | https://www.mdpi.com/2218-273X/15/1/34 |
| work_keys_str_mv | AT kriangkraikiatsoonthon panduratinainhibitstnfalphastimulatedendothelialcellactivationthroughsuppressingthenfkbpathway AT nitchakarnphimthong panduratinainhibitstnfalphastimulatedendothelialcellactivationthroughsuppressingthenfkbpathway AT saranyapinpotikanond panduratinainhibitstnfalphastimulatedendothelialcellactivationthroughsuppressingthenfkbpathway AT nitwarawikan panduratinainhibitstnfalphastimulatedendothelialcellactivationthroughsuppressingthenfkbpathway AT wutigrinimlamool panduratinainhibitstnfalphastimulatedendothelialcellactivationthroughsuppressingthenfkbpathway |