Substantial human and preclinical studies have shown that curcumin, a dietary compound from turmeric, has a variety of health-promoting effects including but not limited to antioxidant, antimicrobial, anti-inflammatory, and anticancer actions. However, curcumin has poor bioavailability, and high doses of curcumin are usually needed to exert its health-promoting effects in vivo, limiting its applications for disease prevention. Here, we discuss the health-promoting effects of curcumin, factors limiting its bioavailability, and strategies to improve its oral bioavailability.

Scope Substantial studies have shown that curcumin, a dietary compound from turmeric, has beneficial effects on many diseases. However, curcumin rapidly degrades at physiological pH, making it difficult to interpret whether the observed actions of curcumin are from curcumin itself or its degradation products. Therefore, it is important to better understand the mechanisms involved in curcumin degradation and the roles of degradation in its biological actions. Methods and results Here, we show that a series of redox active antioxidants with diverse chemical structures, including gallic acid, ascorbate (vitamin C), tert‐butylhydroquinone (TBHQ), caffeic acid, rosmarinic acid, and Trolox (a water‐soluble analog of vitamin E), dramatically increased curcumin stability in phosphate buffer at physiological pH. When treated in basal cell culture medium in MC38 colon cancer cells, curcumin rapidly degraded with a half‐life of several minutes and showed a weak antiproliferative effect; co‐addition of antioxidants enhanced stability and antiproliferative effect of curcumin. Finally, co‐administration of antioxidant significantly increased plasma level of curcumin in animal models. Conclusion Together, these studies strongly suggest that a redox‐dependent mechanism plays a critical role in mediating curcumin degradation. In addition, curcumin itself, instead of its degradation products, is largely responsible for the observed biological actions of curcumin.

Substantial pre-clinical and human studies have shown that curcumin, a dietary compound from turmeric, has a variety of health-promoting biological activities. A better understanding of the biochemical mechanisms for the health-promoting effects of curcumin could facilitate the development of effective strategies for disease prevention. Recent studies have shown that in aqueous buffer, curcumin rapidly degrades and leads to formation of various degradation products. In this review, we summarized and discussed the biological activities of chemical degradation products of curcumin, including alkaline hydrolysis products (such as ferulic acid, vanillin, ferulaldehyde, and feruloyl methane), and autoxidation products (such as bicyclopentadione). Though many of these degradation products are biologically active, they are substantially less-active compared to curcumin, supporting that chemical degradation has a limited contribution to the biological activities of curcumin.

Curcumin, a dietary compound from turmeric, has beneficial effects on inflammatory diseases such as inflammatory bowel disease. Most previous studies have focused on the structure-activity relationship of the thiol-reactive α,β-unsaturated carbonyl groups of curcumin, so little is known about the roles of methoxy groups in biological activities of curcumin. Here we synthesized a series of curcumin analogues with different substitution groups (R = H-, Br-, Cl-, F-, NO-, CH-, and OH-) to replace the methoxy group and evaluated their biological effects in vitro and in vivo. Curcumin, Cur-OH, and Cur-Br (25 μM) suppressed 74.91 ± 0.88, 77.75 ± 0.89, and 71.75 ± 0.90% of LPS-induced NO production, respectively (P < 0.05). Similarly, these compounds also decreased iNOS expression, COX-2 expression, and NF-κB signaling in RAW 264.7 macrophage cells (P < 0.05). However, other analogues, especially Cur-NO, were inactive (P > 0.05). In the dextran sulfate sodium (DSS)-induced colitis mouse model, the Cur-Br analogue also showed a beneficial effect the same as curcumin (P < 0.05), whereas the Cur-NO analogue had no effect in the animal model (P > 0.05). Together, the analogues have dramatically different effects on inflammation, supporting that the substitution group on the methoxy position plays an important role in the anti-inflammatory effects of curcumin. The methoxy group is a potential structural candidate for modification to design curcumin-based drugs for inflammatory diseases.

Many studies have shown that dietary intake of ω-3 polyunsaturated fatty acids (PUFAs) reduces the risks of colorectal cancer, however the underlying mechanisms are not well understood. Here we used a LC-MS/MS-based lipidomics to explore the roles of eicosanoid signaling in the anti-colorectal cancer effects of ω-3 PUFAs. Our results showed that dietary feeding of ω-3 PUFAs-rich diets suppressed growth of MC38 colorectal tumor, and modulated profiles of fatty acids and eicosanoid metabolites in C57BL/6 mice. Notably, we found that dietary feeding of ω-3 PUFAs significantly increased levels of epoxydocosapentaenoic acids (EDPs, metabolites of ω-3 PUFA produced by cytochrome P450 enzymes) in plasma and tumor tissue of the treated mice. We further showed that systematic treatment with EDPs (dose = 0.5 mg/kg/day) suppressed MC38 tumor growth in mice, with reduced expressions of pro-oncogenic genes such as c-myc, Axin2, and C-jun in tumor tissues. Together, these results support that formation of EDPs might contribute to the anti-colorectal cancer effects of ω-3 PUFAs.