Synergistic anticancer effects of curcumin and 3',4'-didemethylnobiletin in combination on colon cancer cells.

Chemoprevention strategies employing the use of multiple dietary bioactive components and their metabolites in combination offer advantages due to their low toxicity and potential synergistic interactions. Herein, for the first time, we studied the combination of curcumin and 3',4'-didemethylnobiletin (DDMN), a primary metabolite of nobiletin, to determine their combinatory effects in inhibiting growth of human colon cancer cells. Isobologram analysis revealed a synergistic interaction between curcumin and DDMN in the inhibition of cell growth of HCT116 colon cancer cells. The combination treatment induced significant G2 -M cell-cycle arrest and extensive apoptosis, which greatly exceeded the effects of individual treatments with curcumin or DDMN. Proteins associated with these heightened anticarcinogenic effects were p53, p21, HO-1, c-poly(ADP-ribose) polymerase, Cdc2, and Cdc25c; each of the proteins was confirmed to be substantially impacted by the combination treatment, more than by individual treatments alone. Interestingly, an increase in the stability of curcumin was also observed with the presence of DDMN in cell culture medium, which could offer an explanation in part for the synergistic interaction between curcumin and DDMN. This newly identified synergy between curcumin and DDMN should be explored further to determine its chemopreventive potential against colon cancer in vivo. PRACTICAL APPLICATION: This study identifies for the first time the synergistic inhibition of colon cancer cell growth by the dietary component curcumin present in turmeric, in combination with a metabolite of nobiletin, a unique citrus flavonoid. The synergism of the combination may be due to cell-cycle arrest and apoptosis induced by the combination as well as an improvement in the stability of curcumin as a result of the antioxidant property of the nobiletin metabolite. These significant findings of synergism between curcumin and the nobiletin metabolite could offer potential chemopreventive value against colon cancer.

Characterization of polymethoxyflavone demethylation during drying processes of citrus peels.

Polymethoxyflavones (PMFs) are found almost exclusively in citrus peel and have attracted much attention due to their potential health benefits. Dried citrus peel is an important ingredient for applications in food and traditional Chinese medicine. However, the structural changes of PMFs during drying processes of citrus peel remain unknown. In this study, for the first time we discovered that four major permethoxylated PMFs, i.e. sinensetin, nobiletin, heptamethoxyflavone and tangeretin, underwent demethylation at the 5-position on the A ring of their flavonoid structures to yield corresponding 5-demethylated PMFs during the drying process of citrus peel. Our results further demonstrated that the aforementioned PMF demethylation was through two mechanisms: acid hydrolysis and enzyme-mediated catalysis. PMF demethylation in citrus peels was systematically characterized during hot-air drying (HAD), vacuum-freeze drying (VFD) and sun drying (SD). The highest PMF demethylation was obtained in SD followed by HAD and VFD. This study provided a solid scientific basis for rational control of PMF demethylation in citrus peels, which could facilitate the production of high-quality citrus peel and related products.

Efficiency of four different dietary preparation methods in extracting functional compounds from dried tangerine peel.

Dried tangerine peel (DTP) is an excellent plant resource that has been used as ingredients for both food and traditional Chinese medicine. In this study, the efficiency of four different dietary preparation methods (i.e. soaking, boiling, steaming, and ethanol extraction) in extraction of functional compounds (i.e. flavonoids and essential oil constituents) from DTP was evaluated systematically for the first time. To conduct a comprehensive evaluation of the extraction of the functional compounds, a synthetic evaluation model based on a weighting method was established. The optimum conditions of each dietary preparation method (e.g., time, temperature, solid-liquid ratio, etc.) were determined by response surface methodology. Ethanol extraction showed the best extraction efficiency, followed by soaking, boiling, and steaming. Additionally, different DTP extracts were shown to be clearly distinguished by electronic eye and electronic tongue. This research provides essential findings for the effective dietary instruction of DTP consumption.

Citrus Oil Emulsions Stabilized by Citrus Pectin: The Influence Mechanism of Citrus Variety and Acid Treatment.

Citrus pectin and citrus oil are the main functional components of citrus residuals in the processing industry. In this study, citrus oil emulsions were fabricated for the first time using four different citrus pectins (orange, mandarin, grapefruit, and commercial citrus pectins) as the emulsifier. The influence mechanism of citrus variety and acid treatment (pH 1, 2, 3, 4, 5, 6, and 7) on the emulsifying capacity of citrus pectins was systematically investigated by understanding the relationship between molecular structure, solution property, interfacial property, and emulsion property. The results suggest that citrus variety and acid treatment can significantly influence the emulsifying capacity in relation to the molecular structure and molecular state of citrus pectins. A smaller molecular size of citrus pectin and lower pH between 2 and 7 produced a reduction in aggregate size, which improved the interfacial capacity and emulsifying ability by promoting their distribution at the interface. Although hydrolyzed citrus pectins at pH 1 with a lower molecular size exhibited better interfacial capacity, citrus oil emulsions were unstable due to electrostatic attraction caused by partially positive charged citrus pectins. Fine stable citrus oil emulsion was prepared using mandarin pectin with a relative high methyl ester content and small molecular size at pH 2. Our results provide a scientific basis for the fabrication of citrus oil emulsion based on citrus pectin and facilitate the application of citrus residuals in the food industry.

The stability of three different citrus oil-in-water emulsions fabricated by spontaneous emulsification.

In this study, emulsions were prepared through spontaneous emulsification, using three different citrus oils as the oil phase and Tween 80 as the surfactant. Utilizing 4% Tween 80, three types of citrus oil emulsions were prepared with small particle size, monomodal distribution and high transmission. After 24 h, each emulsion exhibited different degrees of gravitational separation. Mandarin oil emulsions were the most unstable, showing coalescence of small droplets with an obvious cream layer formed at 9 h. Bergamot oil emulsions possessed small droplets with the best stability over 24 h, due to their relatively polar components (e.g. linalyl acetate) and water-insoluble constituents (e.g. γ-terpinene). These results suggest that the emulsifying properties and instability mechanism of citrus oil emulsions are strongly dependent on the inherent properties and composition of citrus oils. This study is significant for the development of an effective strategy to improve the stability of citrus oil-based colloidal systems.

Diet-based strategies for cancer chemoprevention: the role of combination regimens using dietary bioactive components.

Chemopreventive agents that the general population can consume for prolonged periods of time with minimal risk of any side effects are of great interest to all in search of a solution to the pervasive incidence of cancer. Dietary bioactive components have been found to modulate many deregulated molecular pathways associated with the initiation and progression of different types of cancer. Combination regimens with dietary bioactive components are a promising strategy for cancer chemoprevention because they may offer enhanced protective effects against cancer development but cause little or no adverse effects. This article provides an overview of studies examining the combination of dietary bioactive components for the chemoprevention of major types of cancer. A better understanding of existing research on the combination of dietary bioactive components will provide an important basis for the rational design of future combination studies and the successful development of cancer chemoprevention strategies.