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Metabolomics analysis to evaluate the antiinflammatory effects of polyphenols: glabridin reversed metabolism change caused by LPS in RAW 264.7 cells. Kaiqin Liu, FuWei Pi, Hongxia Zhang, Jian Ji, Shuang Xia, Fangchao Cui, Jiadi Sun, and Xiulan Sun J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.7b01692 • Publication Date (Web): 23 Jun 2017 Downloaded from http://pubs.acs.org on June 24, 2017
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Journal of Agricultural and Food Chemistry is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
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Journal of Agricultural and Food Chemistry
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Metabolomics Analysis To Evaluate The
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Anti-Inflammatory Effects Of Polyphenols: Glabridin
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Reversed Metabolism Change Caused By LPS In
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RAW 264.7 Cells.
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Kaiqin Liua, Fuwei Pia, Hongxia Zhangb, Jian JIa, Shuang Xiaa, Fangchao Cuia,
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Jiadi Suna, Xiulan Suna*
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a
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Technology, National Engineering Research Center for Functional Food,
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Jiangnan University, Wuxi, Jiangsu 214122, PR China
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School of Food Science and Technology, Laboratory of Food Science and
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b
School of Foreign Studies, Shaanxi University of Technology, 723000, China
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Corresponding author*: Xiulan Sun (E-mail:
[email protected])
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Address: Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122,PR
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China.
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E-mail:
[email protected]; Tel:+86-510-85912330
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Fax: 85329015
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running title: Metabolomics Analysis To Evaluate The Anti-Inflammatory Effects
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ABSTRACT:
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Inflammation has been shown to play a critical role in the development of many
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diseases. In this study, we used metabolomics to evaluate the inflammatory effect of
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lipopolysaccharide (LPS) and anti-inflammatory effect of glabridin (GB, a polyphenol
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from Glycurrhiza glabra L. roots) in RAW 264.7 cells. Multivariate statistical analysis
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showed that compared with the LPS group, the metabolic profile of the GB group was
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more similar to that of the control group. LPS impacted the amino acid, energy and
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lipid metabolisms in RAW 264.7 cells and metabolic pathway analysis showed that
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GB reversed some of those LPS impacts. Metabolomics analysis provided us a new
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perspective to better understand the inflammatory response and the anti-inflammatory
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effects of GB. Metabolic pathway analysis can be an effective tool to elucidate the
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mechanism of inflammation and to potentially find new anti-inflammatory agents.
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Keywords:
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anti-inflammatory effect; polyphenols
cells
metabolomics;
metabolism
pathway
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analysis;
LPS;
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Journal of Agricultural and Food Chemistry
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1.Introduction
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Inflammation is a normal protective response of the innate immune system to tissue
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injury or detrimental external stimuli such as pathogens, allergens, and other irritants1.
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Efficient control of inflammation is vital to protect the host from external stimuli.
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Defective resolution of inflammation and ‘misreading’ of inflammatory signals
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increases the risk of developing autoimmune and chronic inflammatory diseases.
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During the inflammatory reaction, immune system cells can recognize foreign
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pathogenic molecules, such as lipopolysaccharide (LPS), which is recognized by
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Toll-like receptors (TLRs) or NOD-like receptors1. This process can lead to the
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activation of major MAP kinase cascades and translocation of the regulator nuclear
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factor-κB (NF-κB) ， resulting in the increased expression of pro-inflammatory
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cytokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α
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(TNF-α), monocyte chemotactic factor 2(CCL-2)2. In addition, it will lead to
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increased expression of nitric oxide (NO) synthase and thus excess NO accumulation.
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Pro-inflammatory cytokines play a key role in some cardiovascular disease (CVD)
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and chronic inflammatory diseases, such as insulin resistance3, diabetes4, 5,
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atherosclerosis6 and depression2, 7.
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Polyphenols are one of the most important group of natural antioxidants and
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chemopreventive agents found in fruits, vegetables, grains, tea and essential oils8, 9.
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Many investigations have repeatedly reported the anti-inflammatory functions of
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different flavonoid molecules, such as suppressing inflammatory cytokines10,
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modulating transcription factors and inflammation-related pathways, reducing 3
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accumulation of NO or reactive oxygen species (ROS). Glabridin (GB) is a
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species-specific isoflavan from Glycurrhiza glabra L. roots. It is reported that its
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biological activities include antimicrobial, anti-inflammatory and cardiovascular
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protective11. GB was found to attenuate LPS-induced production of inflammatory
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mediators, including NO, TNF-α and IL-1β in THP-1 cells12, RAW 264.7 cells13 and
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J774a.1 cells14. GB inhibited dendritic cell maturation by blocking NF-κB and MAPK
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signalings15. Cao et al.16 have performed a pharmacokinetics of GB in
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Sprague-Dawley rats. At 4.5 h after oral administration of 20 mg/kg GB, the peak
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plasma level of GB up to 60.41 ng/mL (
