Subscriber access provided by EAST TENNESSEE STATE UNIV
Article
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
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
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.
Page 1 of 38
Journal of Agricultural and Food Chemistry
1
Metabolomics Analysis To Evaluate The
2
Anti-Inflammatory Effects Of Polyphenols: Glabridin
3
Reversed Metabolism Change Caused By LPS In
4
RAW 264.7 Cells.
5
Kaiqin Liua, Fuwei Pia, Hongxia Zhangb, Jian JIa, Shuang Xiaa, Fangchao Cuia,
6
Jiadi Suna, Xiulan Suna*
7
a
8
Technology, National Engineering Research Center for Functional Food,
9
Jiangnan University, Wuxi, Jiangsu 214122, PR China
*
School of Food Science and Technology, Laboratory of Food Science and
10 11
b
School of Foreign Studies, Shaanxi University of Technology, 723000, China
12 13 14 15 16 17 18
Corresponding author*: Xiulan Sun (E-mail:
[email protected])
19
Address: Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122,PR
20
China.
21
E-mail:
[email protected]; Tel:+86-510-85912330
22
Fax: 85329015
23
running title: Metabolomics Analysis To Evaluate The Anti-Inflammatory Effects
24
1
ACS Paragon Plus Environment
Journal of Agricultural and Food Chemistry
Page 2 of 38
25
ABSTRACT:
26
Inflammation has been shown to play a critical role in the development of many
27
diseases. In this study, we used metabolomics to evaluate the inflammatory effect of
28
lipopolysaccharide (LPS) and anti-inflammatory effect of glabridin (GB, a polyphenol
29
from Glycurrhiza glabra L. roots) in RAW 264.7 cells. Multivariate statistical analysis
30
showed that compared with the LPS group, the metabolic profile of the GB group was
31
more similar to that of the control group. LPS impacted the amino acid, energy and
32
lipid metabolisms in RAW 264.7 cells and metabolic pathway analysis showed that
33
GB reversed some of those LPS impacts. Metabolomics analysis provided us a new
34
perspective to better understand the inflammatory response and the anti-inflammatory
35
effects of GB. Metabolic pathway analysis can be an effective tool to elucidate the
36
mechanism of inflammation and to potentially find new anti-inflammatory agents.
37
Keywords:
38
anti-inflammatory effect; polyphenols
cells
metabolomics;
metabolism
pathway
39 40 41 42 43 44 45 46 2
ACS Paragon Plus Environment
analysis;
LPS;
Page 3 of 38
Journal of Agricultural and Food Chemistry
47
1.Introduction
48
Inflammation is a normal protective response of the innate immune system to tissue
49
injury or detrimental external stimuli such as pathogens, allergens, and other irritants1.
50
Efficient control of inflammation is vital to protect the host from external stimuli.
51
Defective resolution of inflammation and ‘misreading’ of inflammatory signals
52
increases the risk of developing autoimmune and chronic inflammatory diseases.
53
During the inflammatory reaction, immune system cells can recognize foreign
54
pathogenic molecules, such as lipopolysaccharide (LPS), which is recognized by
55
Toll-like receptors (TLRs) or NOD-like receptors1. This process can lead to the
56
activation of major MAP kinase cascades and translocation of the regulator nuclear
57
factor-κB (NF-κB) , resulting in the increased expression of pro-inflammatory
58
cytokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α
59
(TNF-α), monocyte chemotactic factor 2(CCL-2)2. In addition, it will lead to
60
increased expression of nitric oxide (NO) synthase and thus excess NO accumulation.
61
Pro-inflammatory cytokines play a key role in some cardiovascular disease (CVD)
62
and chronic inflammatory diseases, such as insulin resistance3, diabetes4, 5,
63
atherosclerosis6 and depression2, 7.
64
Polyphenols are one of the most important group of natural antioxidants and
65
chemopreventive agents found in fruits, vegetables, grains, tea and essential oils8, 9.
66
Many investigations have repeatedly reported the anti-inflammatory functions of
67
different flavonoid molecules, such as suppressing inflammatory cytokines10,
68
modulating transcription factors and inflammation-related pathways, reducing 3
ACS Paragon Plus Environment
Journal of Agricultural and Food Chemistry
69
accumulation of NO or reactive oxygen species (ROS). Glabridin (GB) is a
70
species-specific isoflavan from Glycurrhiza glabra L. roots. It is reported that its
71
biological activities include antimicrobial, anti-inflammatory and cardiovascular
72
protective11. GB was found to attenuate LPS-induced production of inflammatory
73
mediators, including NO, TNF-α and IL-1β in THP-1 cells12, RAW 264.7 cells13 and
74
J774a.1 cells14. GB inhibited dendritic cell maturation by blocking NF-κB and MAPK
75
signalings15. Cao et al.16 have performed a pharmacokinetics of GB in
76
Sprague-Dawley rats. At 4.5 h after oral administration of 20 mg/kg GB, the peak
77
plasma level of GB up to 60.41 ng/mL (