Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity.
10.4196/kjpp.2015.19.5.441
- Author:
Nak Yoon SUNG
1
;
Mi Yeon KIM
;
Jae Youl CHO
Author Information
1. Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Korea. jaecho@skku.edu
- Publication Type:Original Article
- Keywords:
Anti-inflammatory effect;
Flavonoid;
Macrophages;
NF-kappaB;
Scutellarein;
Src
- MeSH:
Brazil;
China;
Clerodendrum;
Erigeron;
Flavonoids;
Genes, Reporter;
Humans;
Interferon-beta;
Kidney;
Luciferases;
Macrophages;
NF-kappa B;
Nitric Oxide;
Nitric Oxide Synthase;
Phosphorylation;
Phosphotransferases*;
Plants;
Polymerase Chain Reaction;
RNA, Messenger;
Transfection;
Tumor Necrosis Factor-alpha
- From:The Korean Journal of Physiology and Pharmacology
2015;19(5):441-449
- CountryRepublic of Korea
- Language:English
-
Abstract:
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)-alpha in lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, SCT also dampened nuclear factor (NF)-kappaB-driven expression of a luciferase reporter gene upon transfection of a TIR-domain-containing adapter-inducing interferon-beta (TRIF) construct into Human embryonic kidney 293 (HEK 293) cells; similarly, NF-kappa B nuclear translocation was inhibited by SCT. Moreover, the phosphorylation levels of various upstream signaling enzymes involved in NF-kappaB 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-kappaB activation.
