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Front Pharmacol. 2018 Jan 9;8:959. doi: 10.3389/fphar.2017.00959. eCollection 2017.

Traditional Herbal Medicine-Derived Sulforaphene LFS-01 Reverses Colitis in Mice by Selectively Altering the Gut Microbiota and Promoting Intestinal Gamma-Delta T Cells.

Author information

1
Department of Microecology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
2
Center for Molecular Medicine, School of Life Sciences and Biotechnology, Dalian University of Technology, Dalian, China.
3
DrivingForce Therapeutics, Venture Harbor, Dalian, China.
4
School of Software, Dalian University of Technology, Dalian, China.
5
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China.
6
Department of Chemistry and Physics, State University of New York, Stony Brook, NY, United States.

Abstract

Sulforaphene (LFS-01) is a natural compound derived from traditional herbal medicine. Here, we show that oral administration of LFS-01 is able to dramatically alter the skewed gut microbiota and reverse colitis in model mice associated with an increase of intestinal γδT cells. Through 16S rDNA sequencing, we showed that LFS-01 can selectively suppress enteric pathogens such as Escherichia-Shigella and Helicobacter whereas the protective strains including Lactobacillus and Lachnospiraceae were significantly expanded after LFS-01 treatment. Interestingly, we demonstrated that LFS-01 administration can significantly promote the IL-17+γδT cells in model mice in response to the expanded Lactobacillus. We verified that the intracellular components of Lactobacillus can stimulate the growth of IL-17+γδT cells upon preincubation. The increased IL-17A after LFS-01 treatment in turn recovers the disrupted occludin subcellular location and protects the epithelial barrier in the colon of model mice. Remarkably, LFS-01 does not show apparent toxicity to animals and we demonstrated that LFS-01 also exerts strong protective effects in TNBS-induced colitis rats. Therefore, LFS-01 holds great promise for the treatment of inflammatory bowel disease (IBD) and warrants translation for use in clinical trials. Our work provided a new avenue for the treatment of IBD based on the strategy of harnessing intestinal symbiosis.

KEYWORDS:

barrier function; colitis; herbal medicine; microbiota; sulforaphene; γδT cells

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