δ-Tocotrienol, Isolated from Rice Bran, Exerts an Anti-Inflammatory Effect via MAPKs and PPARs Signaling Pathways in Lipopolysaccharide-Stimulated Macrophages

Junjun Shen; Tao Yang; Youzhi Xu; Yi Luo; Xinyue Zhong; Limin Shi; Tao Hu; Tianyi Guo; Ying Nie; Feijun Luo; Qinlu Lin

doi:10.3390/ijms19103022

δ-Tocotrienol, Isolated from Rice Bran, Exerts an Anti-Inflammatory Effect via MAPKs and PPARs Signaling Pathways in Lipopolysaccharide-Stimulated Macrophages

Int J Mol Sci. 2018 Oct 4;19(10):3022. doi: 10.3390/ijms19103022.

Authors

Junjun Shen¹, Tao Yang², Youzhi Xu³, Yi Luo⁴, Xinyue Zhong⁵, Limin Shi⁶, Tao Hu⁷, Tianyi Guo⁸, Ying Nie⁹, Feijun Luo¹⁰, Qinlu Lin¹¹

Affiliations

¹ Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha 410004, Hunan, China. shenjunjun@yeah.net.
² Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha 410004, Hunan, China. yangtao807@163.com.
³ Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha 410004, Hunan, China. xuyouzhi123@hotmail.com.
⁴ Department of Clinic Medicine, Xiangya School of Medicine, Central South University, Changsha 410008, Hunan, China. YiLuo603@hotmail.com.
⁵ Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha 410004, Hunan, China. zhongxinyue111@163.com.
⁶ Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha 410004, Hunan, China. Shilm6666@126.com.
⁷ Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha 410004, Hunan, China. hutao0829@hotmail.com.
⁸ Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha 410004, Hunan, China. guotianyib11@hotmail.com.
⁹ Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha 410004, Hunan, China. ny198722@hotmail.com.
¹⁰ Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha 410004, Hunan, China. luofeijun888@csuft.edu.cn.
¹¹ Hunan Key Laboratory of Grain-Oil Deep Process and Quality Control, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, National Engineering Laboratory for Deep Process of Rice and Byproducts, Central South University of Forestry and Technology, Changsha 410004, Hunan, China. linqinlu@hotmail.com.

Abstract

δ-Tocotrienol, an important component of vitamin E, has been reported to possess some physiological functions, such as anticancer and anti-inflammation, however their molecular mechanisms are not clear. In this study, δ-tocotrienol was isolated and purified from rice bran. The anti-inflammatory effect and mechanism of δ-tocotrienol against lipopolysaccharides (LPS) activated pro-inflammatory mediator expressions in RAW264.7 cells were investigated. Results showed that δ-tocotrienol significantly inhibited LPS-stimulated nitric oxide (NO) and proinflammatory cytokine (TNF-α, IFN-γ, IL-1β and IL-6) production and blocked the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 (ERK1/2). δ-Tocotrienol repressed the transcriptional activations and translocations of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1), which were closely related with downregulated cytokine expressions. Meanwhile, δ-tocotrienol also affected the PPAR signal pathway and exerted an anti-inflammatory effect. Taken together, our data showed that δ-tocotrienol inhibited inflammation via mitogen-activated protein kinase (MAPK) and peroxisome proliferator-activated receptor (PPAR) signalings in LPS-stimulated macrophages.

Keywords: MAPKs; PPARs; RAW264.7; inflammation; rice bran; δ-tocotrienol.

MeSH terms

Animals
Anti-Inflammatory Agents / pharmacology*
Cell Line
Cytokines / metabolism
Lipopolysaccharides / toxicity
MAP Kinase Kinase 4 / metabolism
MAP Kinase Signaling System*
Macrophages / drug effects*
Macrophages / metabolism
Mice
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
NF-kappa B / metabolism
Nitric Oxide / metabolism
Oryza / chemistry*
Peroxisome Proliferator-Activated Receptors / metabolism
Vitamin E / analogs & derivatives*
Vitamin E / analysis
Vitamin E / pharmacology

Substances

Anti-Inflammatory Agents
Cytokines
Lipopolysaccharides
NF-kappa B
Peroxisome Proliferator-Activated Receptors
Vitamin E
tocotrienol, delta
Nitric Oxide
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
MAP Kinase Kinase 4

Abstract

MeSH terms

Substances

Grants and funding