Curcumin and Salsalate Suppresses Colonic Inflammation and Procarcinogenic Signaling in High-Fat-Fed, Azoxymethane-Treated Mice.

Abstract

High-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.

• Authors: Xian Wu, Anna C Pfalzer, Gar Yee Koh, Sanyuan Tang, Jimmy W Crott, Michael J Thomas, Mohsen Meydani, Joel B Mason
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 65 Issue 33 Pg. 7200-7209 (Aug 23 2017) ISSN: 1520-5118 [Electronic] United States
• PMID: 28745498 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Interleukin-6
• NF-kappa B
• Salicylates
• Curcumin
• Azoxymethane
• salicylsalicylic acid

Topics

• Animals
• Anti-Inflammatory Agents
• Azoxymethane (adverse effects)
• Colorectal Neoplasms (chemically induced, drug therapy, genetics, immunology)
• Curcumin (administration & dosage)
• Diet, High-Fat (adverse effects)
• Humans
• Interleukin-6 (genetics, immunology)
• Male
• Mice
• NF-kappa B (genetics, immunology)
• Salicylates (administration & dosage)