TAK1/AP-1-Targeted Anti-Inflammatory Effects of <i>Barringtonia augusta</i> Methanol Extract
<i>Barringtonia augusta</i> methanol extract (Ba-ME) is a folk medicine found in the wetlands of Thailand that acts through an anti-inflammatory mechanism that is not understood fully. Here, we examine how the methanol extract of <i>Barringtonia augusta</i> (<i>B. augus...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/10/3053 |
| _version_ | 1827691960506253312 |
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| author | Anh Thu Ha Mi-Yeon Kim Jae Youl Cho |
| author_facet | Anh Thu Ha Mi-Yeon Kim Jae Youl Cho |
| author_sort | Anh Thu Ha |
| collection | DOAJ |
| description | <i>Barringtonia augusta</i> methanol extract (Ba-ME) is a folk medicine found in the wetlands of Thailand that acts through an anti-inflammatory mechanism that is not understood fully. Here, we examine how the methanol extract of <i>Barringtonia augusta</i> (<i>B. augusta)</i> can suppress the activator protein 1 (AP-1) signaling pathway and study the activities of Ba-ME in the lipopolysaccharide (LPS)-treated RAW264.7 macrophage cell line and an LPS-induced peritonitis mouse model. Non-toxic concentrations of Ba-ME downregulated the mRNA expression of cytokines, such as cyclooxygenase and chemokine ligand 12, in LPS-stimulated RAW264.7 cells. Transfection experiments with the AP-1-Luc construct, HEK293T cells, and luciferase assays were used to assess whether Ba-ME suppressed the AP-1 functional activation. A Western blot assay confirmed that C-Jun N-terminal kinase is a direct pharmacological target of Ba-ME action. The anti-inflammatory effect of Ba-ME, which functions by β-activated kinase 1 (TAK1) inhibition, was confirmed by using an overexpression strategy and a cellular thermal shift assay. In vivo experiments in a mouse model of LPS-induced peritonitis showed the anti-inflammatory effect of Ba-ME on LPS-stimulated macrophages and acute inflammatory mouse models. We conclude that Ba-ME is a promising anti-inflammatory drug targeting TAK1 in the AP-1 pathway. |
| first_indexed | 2024-03-10T11:12:49Z |
| format | Article |
| id | doaj.art-01fba81121b2405f9ecfb3d93e2a31d1 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T11:12:49Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-01fba81121b2405f9ecfb3d93e2a31d12023-11-21T20:36:20ZengMDPI AGMolecules1420-30492021-05-012610305310.3390/molecules26103053TAK1/AP-1-Targeted Anti-Inflammatory Effects of <i>Barringtonia augusta</i> Methanol ExtractAnh Thu Ha0Mi-Yeon Kim1Jae Youl Cho2Department of Integrative Biotechnology, and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, KoreaSchool of Systems Biomedical Science, Soongsil University, Seoul 06978, KoreaDepartment of Integrative Biotechnology, and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea<i>Barringtonia augusta</i> methanol extract (Ba-ME) is a folk medicine found in the wetlands of Thailand that acts through an anti-inflammatory mechanism that is not understood fully. Here, we examine how the methanol extract of <i>Barringtonia augusta</i> (<i>B. augusta)</i> can suppress the activator protein 1 (AP-1) signaling pathway and study the activities of Ba-ME in the lipopolysaccharide (LPS)-treated RAW264.7 macrophage cell line and an LPS-induced peritonitis mouse model. Non-toxic concentrations of Ba-ME downregulated the mRNA expression of cytokines, such as cyclooxygenase and chemokine ligand 12, in LPS-stimulated RAW264.7 cells. Transfection experiments with the AP-1-Luc construct, HEK293T cells, and luciferase assays were used to assess whether Ba-ME suppressed the AP-1 functional activation. A Western blot assay confirmed that C-Jun N-terminal kinase is a direct pharmacological target of Ba-ME action. The anti-inflammatory effect of Ba-ME, which functions by β-activated kinase 1 (TAK1) inhibition, was confirmed by using an overexpression strategy and a cellular thermal shift assay. In vivo experiments in a mouse model of LPS-induced peritonitis showed the anti-inflammatory effect of Ba-ME on LPS-stimulated macrophages and acute inflammatory mouse models. We conclude that Ba-ME is a promising anti-inflammatory drug targeting TAK1 in the AP-1 pathway.https://www.mdpi.com/1420-3049/26/10/3053<i>Barringtonia augusta</i>anti-inflammatory effectTAK1 |
| spellingShingle | Anh Thu Ha Mi-Yeon Kim Jae Youl Cho TAK1/AP-1-Targeted Anti-Inflammatory Effects of <i>Barringtonia augusta</i> Methanol Extract Molecules <i>Barringtonia augusta</i> anti-inflammatory effect TAK1 |
| title | TAK1/AP-1-Targeted Anti-Inflammatory Effects of <i>Barringtonia augusta</i> Methanol Extract |
| title_full | TAK1/AP-1-Targeted Anti-Inflammatory Effects of <i>Barringtonia augusta</i> Methanol Extract |
| title_fullStr | TAK1/AP-1-Targeted Anti-Inflammatory Effects of <i>Barringtonia augusta</i> Methanol Extract |
| title_full_unstemmed | TAK1/AP-1-Targeted Anti-Inflammatory Effects of <i>Barringtonia augusta</i> Methanol Extract |
| title_short | TAK1/AP-1-Targeted Anti-Inflammatory Effects of <i>Barringtonia augusta</i> Methanol Extract |
| title_sort | tak1 ap 1 targeted anti inflammatory effects of i barringtonia augusta i methanol extract |
| topic | <i>Barringtonia augusta</i> anti-inflammatory effect TAK1 |
| url | https://www.mdpi.com/1420-3049/26/10/3053 |
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