Subscriber access provided by CAL STATE UNIV SAN FRANCISCO
Article
Curcumin and Salsalate Suppresses Colonic Inflammation and ProCarcinogenic Signaling in High-Fat Fed, Azoxymethane-Treated Mice Xian Wu, Anna C Pfalzer, Gar Yee Koh, Sanyuan Tang, Jimmy W Crott, Michael J Thomas, Mohsen Meydani, and Joel B Mason J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.7b02648 • Publication Date (Web): 26 Jul 2017 Downloaded from http://pubs.acs.org on July 27, 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 30
Journal of Agricultural and Food Chemistry
Curcumin and Salsalate Suppresses Colonic Inflammation and Pro-Carcinogenic Signaling in High-Fat Fed, Azoxymethane-Treated Mice Xian Wu1 *, Anna C. Pfalzer1,3, Gar Yee Koh1, Sanyuan Tang1,6, Jimmy W. Crott1,3, Michael J. Thomas2, Mohsen Meydani2, Joel B. Mason1,3,4,5 * 1
Vitamins & Carcinogenesis and 2Vascular Biology Laboratories, Jean Mayer U.S.D.A. Human Nutrition
Research Center on Aging at Tufts University University
4
Division of Gastroenterology and
5
3
Friedman School of Nutrition Science and Policy, Tufts
Division of Clinical Nutrition, Tufts Medical Center
6
The First
Affiliated Hospital, University of South China, Hengyang, Hunan, P.R. China
*Corresponding author: Joel B. Mason,
[email protected], USDA HNRCA at Tufts University. 711 Washington St, Boston, MA 02111. Tel. 617-556-3194/FAX 617-556-3234
Xian Wu,
[email protected], USDA HNRCA at Tufts University. 711 Washington St, Boston, MA 02111.
Sources of support: Funded in part by the Agricultural Research Service, Cooperative Agreement #58-1950-0014 (JBM and JWC), a Tufts Collaborates Grant (JBM), the Drs. Joan and Peter Cohn Research Award and HNRCA Director’s Student Innovation Fund (ACP). Any opinions, findings, conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the U.S. Department of Agriculture. We thank the Sabinsa Corporation for their generous donation of the curcumin. Disclaimers: none Short running head: Curcumin and salsalate reduce inflammation and pro-carcinogenic signaling in high-fat fed mice Abbreviations: CUR, curcumin; SAL, salsalate; AOM, azoxymethane; HFD, high fat diet; LFD, low fat diet; CRC, colorectal cancer; NSAID, non-steroidal anti-inflammatory drug; BMI, body mass index; TNF-α, tumor necrosis factor α; IL-1β, interleukin-1β; IL-6, interleukin-6; Akt, protein kinase B; NF-κB, nuclear factor-κB.
ACS Paragon Plus Environment
Journal of Agricultural and Food Chemistry
1
Page 2 of 30
Abstract
2
High fat diets (HFD) and excess adiposity increase pro-inflammatory cytokines in the colon, altering gene
3
expression in a manner that promotes the development of colorectal cancer (CRC). Thus, compounds that reduce
4
this biochemical inflammation are potential chemopreventive agents. Curcumin (CUR), a dietary polyphenol, and
5
salsalate (SAL), a non-steroidal anti-inflammatory drug, are both anti-inflammatory. We investigated the
6
inhibitory effects of CUR with or without SAL on inflammatory cytokines and pro-carcinogenic signaling in
7
azoxymethane (AOM)-treated A/J mice. A sub-tumorigenic AOM dose was chosen to produce a biochemical and
8
molecular pro-carcinogenic colonic environment without tumors. Mice were fed either a high- (60% of kcals) or
9
low- (10%) fat diet (LFD). One HFD treatment group received 0.2% CUR in the diet, one received 0.2%
10
CUR+0.15% SAL, and one received 0.4% CUR+0.3% SAL. The HFD-mice developed 30% greater fat mass than
11
did LFD-mice (p
