[en] Dietary choline and its containing foods are biotransformed to trimethylamine (TMA) via gut microbial metabolism. Subsequently, as an intermediate molecule, TMA is quickly transported and oxidized in the liver by hepatic flavin monooxygenases to form trimethylamine oxide (TMAO). TMAO was treated as a waste byproduct from choline metabolism, but recent convincing evidence demonstrated the association between the small molecule TMAO and inflammation-related diseases, including blood vessel inflammation and vascular diseases. The scope of this study is to investigate the preventive effect of nobiletin on TMAO-induced blood vessel inflammation. Our results from Western blot showed that the inhibition of TMAO-induced cardiovascular inflammation was correlated with nobiletin-mediated inhibitory effects on NF-κB and MAPK/ERK related pathways. More specifically, nobiletin prevented the oxidative damage of vascular sites (proximal aorta), inhibited the activity of MAPK/ERK, reduced the expression of NF-κB p65 and phospho-NF-κB p65, and consequently decreased the inflammatory response. Flow cytometry analyses showed that nobiletin decreased TMAO-induced apoptosis of HUVEC cells and counteracted TMAO-induced HUVEC cell proliferation. Results from HE staining and immunohistochemical results also showed that nobiletin reduced the degree of inflammation of the proximal aorta in Sprague-Dawley rats. In summary, nobiletin significantly reduced TMAO-induced vascular inflammation via inhibition of the NF-κB/MAPK pathways.
Disciplines :
Food science
Author, co-author :
Yang, Guliang; Hubei Key Laboratory of EFGIR , Huanggang Normal University , Huanggang , Hubei 438000 , China ; Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science , Tianjin University of Commerce , Tianjin 300072 , China ; National Engineering Laboratory for Rice and Byproducts Processing, Food Science and Engineering College , Central South University of Forestry and Technology , Changsha , Hunan 410004 , China
Lin, Chi-Chen; Institute of Biomedical Science , National Chung-Hsing University , Taichung 40227 , Taiwan
Yang, Yiwen; Hubei Key Laboratory of EFGIR , Huanggang Normal University , Huanggang , Hubei 438000 , China
Yuan, Li; Hubei Key Laboratory of EFGIR , Huanggang Normal University , Huanggang , Hubei 438000 , China
Wang, Peilei; Hubei Key Laboratory of EFGIR , Huanggang Normal University , Huanggang , Hubei 438000 , China
Wen, Xiang ; Université de Liège - ULiège > GIGA > GIGA Stem Cells - Medical Chemistry ; Hubei Key Laboratory of EFGIR , Huanggang Normal University , Huanggang , Hubei 438000 , China ; Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science , Tianjin University of Commerce , Tianjin 300072 , China
Pan, Min-Hsiung ; Institute of Food Sciences and Technology , National Taiwan University , Taipei 10617 , Taiwan
Zhao, Hui ; Tianjin Key Laboratory of Food and Biotechnology, School of Biotechnology and Food Science , Tianjin University of Commerce , Tianjin 300072 , China
Ho, Chi-Tang; Department of Food Science , Rutgers University , New Brunswick , New Jersey 08901 , United States
Li, Shiming ; Hubei Key Laboratory of EFGIR , Huanggang Normal University , Huanggang , Hubei 438000 , China
Language :
English
Title :
Nobiletin Prevents Trimethylamine Oxide-Induced Vascular Inflammation via Inhibition of the NF-κB/MAPK Pathways.
NSCF - National Natural Science Foundation of China [CN]
Funding text :
National Nature Science Fund of China (SL, Grant No. 31571832), Tianjin Innovative Research Team Grant (TD13-5087), and Tianjin Key Laboratory of Food Biotechnology Grant (H.Z., TJCU-KLFB-18101).
