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Curcumin and Salsalate Suppresses Colonic Inflammation and Procarcinogenic Signaling in High-Fat-Fed, Azoxymethane-Treated Mice
journal contribution
posted on 2017-07-26, 00:00 authored by Xian Wu, Anna C. Pfalzer, Gar Yee Koh, Sanyuan Tang, Jimmy W. Crott, Michael J. Thomas, Mohsen Meydani, Joel B. MasonHigh-fat diets (HFDs) and excess
adiposity increase proinflammatory
cytokines in the colon, altering gene expression in a manner that
promotes the development of colorectal cancer (CRC). Thus, compounds
that reduce this biochemical inflammation are potential chemopreventive
agents. Curcumin (CUR), a dietary polyphenol, and salsalate (SAL),
a non-steroidal anti-inflammatory drug, are both anti-inflammatories.
We investigated the inhibitory effects of CUR with or without SAL
on inflammatory cytokines and procarcinogenic signaling in azoxymethane
(AOM)-treated A/J mice. A sub-tumorigenic AOM dose was chosen to produce
a biochemical and molecular procarcinogenic colonic environment without
tumors. Mice were fed either a HFD (60% of kilocalories) or low-fat
diet (LFD) (10% of kilocalories). One HFD treatment group received
0.2% CUR in the diet; one received 0.2% CUR + 0.15% SAL; and one received
0.4% CUR + 0.3% SAL. The HFD mice developed 30% greater fat mass than
the LFD mice (p < 0.05). The colonic concentrations
of interleukin-1β (IL-1β) and interleukin-6 (IL-6) in
the HFD mice were decreased by 50–69% by the high-dose combination
regimen (p < 0.015). Only the combination regimens
significantly suppressed phosphorylation of protein kinase B (Akt)
and nuclear factor-κB (NF-κB) p65 (p <
0.044). The combination of CUR and SAL reduces the concentration of
proinflammatory cytokines and diminishes activation of Akt and NF-κB
more effectively than CUR alone, providing a scientific basis for
examining whether this combination mitigates the risk of CRC in obese
individuals.