Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity
Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not f...
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The Korean Physiological Society and The Korean Society of Pharmacology
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553404/ |
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pubmed-45534042015-09-01 Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity Sung, Nak Yoon Kim, Mi-Yeon Cho, Jae Youl Original Article Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not fully elucidated yet. In this study, we aimed to evaluate the anti-inflammatory mechanism of scutellarein (SCT), a flavonoid isolated from Erigeron breviscapus, Clerodendrum phlomidis and Oroxylum indicum Vent that have been traditionally used to treat various inflammatory diseases in China and Brazil. For this purpose, a nitric oxide (NO) assay, polymerase chain reaction (PCR), nuclear fractionation, immunoblot analysis, a kinase assay, and an overexpression strategy were employed. Scutellarein significantly inhibited NO production in a dose-dependent manner and reduced the mRNA expression levels of inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, SCT also dampened nuclear factor (NF)-κB-driven expression of a luciferase reporter gene upon transfection of a TIR-domain-containing adapter-inducing interferon-β (TRIF) construct into Human embryonic kidney 293 (HEK 293) cells; similarly, NF-κ B nuclear translocation was inhibited by SCT. Moreover, the phosphorylation levels of various upstream signaling enzymes involved in NF-κB activation were decreased by SCT treatment in LPS-treated RAW264.7 cells. Finally, SCT strongly inhibited Src kinase activity and also inhibited the autophosphorylation of overexpressed Src. Therefore, our data suggest that SCT can block the inflammatory response by directly inhibiting Src kinase activity linked to NF-κB activation. The Korean Physiological Society and The Korean Society of Pharmacology 2015-09 2015-08-20 /pmc/articles/PMC4553404/ /pubmed/26330757 http://dx.doi.org/10.4196/kjpp.2015.19.5.441 Text en Copyright © 2015 The Korean Physiological Society and The Korean Society of Pharmacology http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Sung, Nak Yoon Kim, Mi-Yeon Cho, Jae Youl |
| spellingShingle |
Sung, Nak Yoon Kim, Mi-Yeon Cho, Jae Youl Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity |
| author_facet |
Sung, Nak Yoon Kim, Mi-Yeon Cho, Jae Youl |
| author_sort |
Sung, Nak Yoon |
| title |
Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity |
| title_short |
Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity |
| title_full |
Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity |
| title_fullStr |
Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity |
| title_full_unstemmed |
Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity |
| title_sort |
scutellarein reduces inflammatory responses by inhibiting src kinase activity |
| description |
Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not fully elucidated yet. In this study, we aimed to evaluate the anti-inflammatory mechanism of scutellarein (SCT), a flavonoid isolated from Erigeron breviscapus, Clerodendrum phlomidis and Oroxylum indicum Vent that have been traditionally used to treat various inflammatory diseases in China and Brazil. For this purpose, a nitric oxide (NO) assay, polymerase chain reaction (PCR), nuclear fractionation, immunoblot analysis, a kinase assay, and an overexpression strategy were employed. Scutellarein significantly inhibited NO production in a dose-dependent manner and reduced the mRNA expression levels of inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, SCT also dampened nuclear factor (NF)-κB-driven expression of a luciferase reporter gene upon transfection of a TIR-domain-containing adapter-inducing interferon-β (TRIF) construct into Human embryonic kidney 293 (HEK 293) cells; similarly, NF-κ B nuclear translocation was inhibited by SCT. Moreover, the phosphorylation levels of various upstream signaling enzymes involved in NF-κB activation were decreased by SCT treatment in LPS-treated RAW264.7 cells. Finally, SCT strongly inhibited Src kinase activity and also inhibited the autophosphorylation of overexpressed Src. Therefore, our data suggest that SCT can block the inflammatory response by directly inhibiting Src kinase activity linked to NF-κB activation. |
| publisher |
The Korean Physiological Society and The Korean Society of Pharmacology |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553404/ |
| _version_ |
1613470427839987712 |