Cacao beans contain abundant polyphenols such as catechins and their polymers procyanidins. Intake of cacao product in particular dark chocolate has various health promotion effects including prevention of lifestyle diseases. We here show that prevention effects of cacao polyphenols on hyperglycemia and adiposity: Cacao polyphenols promote translocation of glucose transporter 4 to the plasma membrane of muscle cells accompanied by phosphorylation of AMP-activated kinase (AMPK) and GLP-1 secretion; and they increase energy expenditure-related factors such as uncoupling proteins and peroxisome proliferator-activated receptor gamma coactivator 1 trough phosphorylation of AMPK.

Flavonols are a class of flavonoids that consist of a large group of polyphenols. Epidemiological studies have suggested that flavonols, including quercetin, have a protective effect against cardiocascular diseases. Onions are the major food source of quercetin in Japan. The mean estimated quercetin intakes by residents of a town in Japan were 15-16 mg (as quercetin aglycon) / day in summer and winter. Recently, quercetin-rich onion ‘Quergold’ containing about 75 mg quercetin / 100 g of fresh weight in the edible portion is registered. Dietary patterns have been reported to be associated with risks of dementia and Altzheimer’s diseases. Dietary administration of quercetin was shown to improve the cognitive function in both Altzheimer’s disease model mice and healthy aged mice. The results of intervention trials suggested that consumption of quercetin rich onion improved memory recall in early-stage Alzheimer’s patients, and cognitive function in elderly people. Quercetin-rich onion is expected to be contribute to prevent lifestyle-related diseases and cognitive decline through dietary life.

Much attention has long been paid on the biological activity of dietary flavonoids in human health. Although flavonoids and other polyphenols are metabolized into their phase-II conjugates, glucuronides and sulfates, after absorption in vivo, the actions of these conjugates underlying the health-beneficial activity, including the target sites/molecules, have not been understood. Here, this review summarized our recent findings on the molecular mechanisms for specific accumulation of quercetin-3-glucuronide, a major quercetin metabolite found in human plasma, in macrophages and the following deconjugation into the biologically active aglycones. Understanding how flavonoid conjugates could exhibit their biological activity in specific tissues and cells will provide useful information in developing new strategies for the effective utilization of the biological activity of natural flavonoids in daily diet.

Although understanding the high-resolution spatial distribution of bioactive small molecules is indispensable for elucidating their biological or pharmacological effects, there has been no analytical technique that can easily visualize the naïve molecular localization in mammalian tissues. In this review, we represent a novel in situ label-free imaging technique of bioactive small molecules, such as polyphenol. A matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) technique visualized epigallocatechin-3-O-gallate (EGCG), the major bioactive green tea polyphenol, within mouse tissue micro-regions after oral dosing. Furthermore, the combination of this label-free MALDI-MSI method and a standard-independent metabolite identification method allowed for the visualization of spatially-resolved biotransformation based on simultaneous mapping of EGCG and its phase II metabolites. This approach will overcome the drawbacks associated with conventional molecular imaging techniques, and could contribute to biological discovery.

Polyphenols are abundant phytochemicals in many plant diet, and reveal many benefits to human health, of which, the antioxidant activities have been considered as a major role. Although polyphenols show higher antioxidant activities in vitro, their bioavailability are very low. Thus, the antioxidant activities in vivo are limited. Recent studies revealed that some of polyphenols or their metabolites could modulate some protein kinases locating in the cellular signaling cascades, and could directly bind to the protein kinases and modulate their activations. These modulations by polyphenols finally regulate signaling transductions and the expressions of many downstream genes. In this review, we summarize the recent results on the molecular targets of polyphenols based on the interactions of polyphenols and the target proteins.