Prevention of Vascular Inflammation by Pterostilbene via Trimethylamine-N-Oxide Reduction and Mechanism of Microbiota Regulation.

Abstract

SCOPE:

A gut-microbiota-dependent metabolite of L-carnitine, trimethylamine-N-oxide (TMAO), has been recently discovered as an independent and dose-dependent risk factor for cardiovascular disease (CVD). This study aims to investigate the effects of pterostilbene on reducing TMAO formation and on decreasing vascular inflammation in carnitine-feeding mice.

METHODS AND RESULTS:

C57BL/6 mice are treated with 1.3% carnitine in drinking water with or without pterostilbene supplementation. Using LC-MS/MS, the result shows that mice treated with 1.3% carnitine only significantly increased the plasma TMAO and pterostilbene supplementation group can reverse it. Additionally, pterostilbene decreases hepatic flavin monooxygenase 3 (FMO3) mRNA levels compared to carnitine only group. It appears that pterostilbene can alter host physiology and create an intestinal microenvironment favorable for certain gut microbiota. Gut microbiota analysis reveals that pterostilbene increases the abundance of Bacteroides. Further, pterostilbene decreases mRNA levels of vascular inflammatory markers tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin).

CONCLUSION:

These data suggest that amelioration of carnitine-induced vascular inflammation after consumption of pterostilbene is partially mediated via modulation of gut microbiota composition and hepatic enzyme FMO3 gene expression.

• Authors: Yen-Chun Koh, Shiming Li, Pei-Yu Chen, Jia-Ching Wu, Nagabhushanam Kalyanam, Chi-Tang Ho, Min-Hsiung Pan
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 63 Issue 20 Pg. e1900514 (10 2019) ISSN: 1613-4133 [Electronic] Germany
• PMID: 31368236 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Methylamines
• Stilbenes
• Tumor Necrosis Factor-alpha
• pterostilbene
• Oxygenases
• dimethylaniline monooxygenase (N-oxide forming)
• trimethyloxamine
• Carnitine

Topics

• Animals
• Carnitine (toxicity)
• Female
• Gastrointestinal Microbiome (physiology)
• Methylamines (metabolism)
• Mice
• Mice, Inbred C57BL
• Oxidation-Reduction
• Oxygenases (genetics)
• Stilbenes (pharmacology)
• Tumor Necrosis Factor-alpha (genetics)
• Vasculitis (prevention & control)