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Crocetin Exerts Its Anti-inflammatory Property in LPS-Induced RAW264.7 Cells Potentially via Modulation on the Crosstalk between MEK1/JNK/NF-κB/iNOS Pathway and Nrf2/HO-1 Pathway
Crocetin is a main bioactive component with a carotenoid skeleton in Gardenia jasminoides, a typical traditional Chinese medicine with a long history in Southeast Asia. Crocetin is being commonly consumed as spices, dyes, and food colorants. Recent pharmacological studies had implied that crocetin m...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449229/ https://www.ncbi.nlm.nih.gov/pubmed/34545298 http://dx.doi.org/10.1155/2021/6631929 |
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author | Wen, Yi-Ling He, Ziyu Hou, De-Xing Qin, Si |
author_facet | Wen, Yi-Ling He, Ziyu Hou, De-Xing Qin, Si |
author_sort | Wen, Yi-Ling |
collection | PubMed |
description | Crocetin is a main bioactive component with a carotenoid skeleton in Gardenia jasminoides, a typical traditional Chinese medicine with a long history in Southeast Asia. Crocetin is being commonly consumed as spices, dyes, and food colorants. Recent pharmacological studies had implied that crocetin may possess potent anti-inflammatory properties; however, the underlying molecular mechanism is not fully elucidated. In the present study, the regulatory effect of crocetin on redox balance was systematically investigated in lipopolysaccharide- (LPS-) stimulated RAW264.7 cells. The results showed that crocetin dose-dependently inhibited LPS-induced nitric oxide production and inducible nitric oxide synthase (iNOS) expression in RAW264.7 cells. Molecular data revealed that crocetin exerted its anti-inflammatory property by inhibiting the MEK1/JNK/NF-κB/iNOS pathway and activating the Nrf2/HO-1 pathway. The shRNA-knockdown (KD) of MEK1 and ERK1 confirmed that the activation of MEK1 and inhibition of JNK mediated the anti-inflammatory effect of crocetin. Moreover, the pull-down assay and computational molecule docking showed that crocetin could directly bind to MEK1 and JNK1/2. It is noticed that both KD and knockout (KO) of HO-1 gene blocked this action. More detailed data have shown that HO-1-KO blocked the inhibition of p-IκB-α by crocetin. These data indicated that crocetin exerted its anti-inflammatory property via modulating the crosstalk between the MEK1/JNK/NF-κB/iNOS pathway and the Nrf2/HO-1 pathway, highlighting HO-1 as a major player. Therefore, the present study reveals that crocetin can act as a potential candidate for redox-balancing modulation in charge of its anti-inflammatory and chemopreventive effect, which strengthens its potency in the subsequent clinic application in the near future. |
format | Online Article Text |
id | pubmed-8449229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-84492292021-09-19 Crocetin Exerts Its Anti-inflammatory Property in LPS-Induced RAW264.7 Cells Potentially via Modulation on the Crosstalk between MEK1/JNK/NF-κB/iNOS Pathway and Nrf2/HO-1 Pathway Wen, Yi-Ling He, Ziyu Hou, De-Xing Qin, Si Oxid Med Cell Longev Research Article Crocetin is a main bioactive component with a carotenoid skeleton in Gardenia jasminoides, a typical traditional Chinese medicine with a long history in Southeast Asia. Crocetin is being commonly consumed as spices, dyes, and food colorants. Recent pharmacological studies had implied that crocetin may possess potent anti-inflammatory properties; however, the underlying molecular mechanism is not fully elucidated. In the present study, the regulatory effect of crocetin on redox balance was systematically investigated in lipopolysaccharide- (LPS-) stimulated RAW264.7 cells. The results showed that crocetin dose-dependently inhibited LPS-induced nitric oxide production and inducible nitric oxide synthase (iNOS) expression in RAW264.7 cells. Molecular data revealed that crocetin exerted its anti-inflammatory property by inhibiting the MEK1/JNK/NF-κB/iNOS pathway and activating the Nrf2/HO-1 pathway. The shRNA-knockdown (KD) of MEK1 and ERK1 confirmed that the activation of MEK1 and inhibition of JNK mediated the anti-inflammatory effect of crocetin. Moreover, the pull-down assay and computational molecule docking showed that crocetin could directly bind to MEK1 and JNK1/2. It is noticed that both KD and knockout (KO) of HO-1 gene blocked this action. More detailed data have shown that HO-1-KO blocked the inhibition of p-IκB-α by crocetin. These data indicated that crocetin exerted its anti-inflammatory property via modulating the crosstalk between the MEK1/JNK/NF-κB/iNOS pathway and the Nrf2/HO-1 pathway, highlighting HO-1 as a major player. Therefore, the present study reveals that crocetin can act as a potential candidate for redox-balancing modulation in charge of its anti-inflammatory and chemopreventive effect, which strengthens its potency in the subsequent clinic application in the near future. Hindawi 2021-09-10 /pmc/articles/PMC8449229/ /pubmed/34545298 http://dx.doi.org/10.1155/2021/6631929 Text en Copyright © 2021 Yi-Ling Wen et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Wen, Yi-Ling He, Ziyu Hou, De-Xing Qin, Si Crocetin Exerts Its Anti-inflammatory Property in LPS-Induced RAW264.7 Cells Potentially via Modulation on the Crosstalk between MEK1/JNK/NF-κB/iNOS Pathway and Nrf2/HO-1 Pathway |
title | Crocetin Exerts Its Anti-inflammatory Property in LPS-Induced RAW264.7 Cells Potentially via Modulation on the Crosstalk between MEK1/JNK/NF-κB/iNOS Pathway and Nrf2/HO-1 Pathway |
title_full | Crocetin Exerts Its Anti-inflammatory Property in LPS-Induced RAW264.7 Cells Potentially via Modulation on the Crosstalk between MEK1/JNK/NF-κB/iNOS Pathway and Nrf2/HO-1 Pathway |
title_fullStr | Crocetin Exerts Its Anti-inflammatory Property in LPS-Induced RAW264.7 Cells Potentially via Modulation on the Crosstalk between MEK1/JNK/NF-κB/iNOS Pathway and Nrf2/HO-1 Pathway |
title_full_unstemmed | Crocetin Exerts Its Anti-inflammatory Property in LPS-Induced RAW264.7 Cells Potentially via Modulation on the Crosstalk between MEK1/JNK/NF-κB/iNOS Pathway and Nrf2/HO-1 Pathway |
title_short | Crocetin Exerts Its Anti-inflammatory Property in LPS-Induced RAW264.7 Cells Potentially via Modulation on the Crosstalk between MEK1/JNK/NF-κB/iNOS Pathway and Nrf2/HO-1 Pathway |
title_sort | crocetin exerts its anti-inflammatory property in lps-induced raw264.7 cells potentially via modulation on the crosstalk between mek1/jnk/nf-κb/inos pathway and nrf2/ho-1 pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449229/ https://www.ncbi.nlm.nih.gov/pubmed/34545298 http://dx.doi.org/10.1155/2021/6631929 |
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