Investigation on the Epoxidation of Piperitenone, and Structure-activity Relationships of Piperitenone Oxide for Differentiation-inducing Activity.

Piperitenone oxide, a major chemical constituent of the essential oil of spearmint, Mentha spicata, induces differentiation in human colon cancer RCM-1 cells. In this study, piperitenone oxide and trans-piperitenone dioxide were prepared as racemic forms by epoxidation of piperitenone. The relative configuration between two epoxides in piperitenone dioxide was determined to be trans by 1H NMR analysis and nuclear Overhauser effect spectroscopy (NOESY) in conjunction with density functional theory (DFT) calculations. Optical resolution of (±)-piperitenone oxide by high-performance liquid chromatography (HPLC) using a chiral stationary phase (CSP) afforded both enantiomers with over 98% enantiomeric excess (ee). Evaluation of the differentiation-inducing activity of the synthetic compounds revealed that the epoxide at C-1 and C-6 in piperitenone oxide is important for the activity, and (+)-piperitenone oxide has stronger activity than (-)-piperitenone oxide. The results obtained in this study provide new information on the application of piperitenone oxide and spearmint for differentiation-inducing therapy. Furthermore, natural piperitenone oxide was isolated from M. spicata. The enantiomeric excess of the isolated natural piperitenone oxide was 66% ee. Epoxidation of piperitenone with hydrogen peroxide proceeded in a phosphate buffer under weak basic conditions to give (±)-piperitenone oxide. These results suggest that the nonenzymatic epoxidation of piperitenone, which causes a decrease in the enantiomeric excess of natural piperitenone oxide, is accompanied by an enzymatic epoxidation in the biosynthesis of piperitenone oxide.

Contribution of Katsura-uri (Japan's Heirloom Pickling Melon, Cucumis melo var. conomon) at the Completely Ripe Stage to Diabetes Control.

The fruit of Katsura-uri (Japan's heirloom pickling melon, Cucumis melo var. conomon) possesses a fruity aroma and moderate sweetness. The fruit juice has potential to minimize human postprandial blood glucose levels. This study provides information regarding the health benefits of Katsura-uri and its utility in treating diabetes. The study methodology involved measuring the color and firmness of Katsura-uri fruit at five ripening stages, and quantitation of the aroma substances, proximate composition, and sugars. Significant changes were detected in the color, firmness, and level of aroma substances with ripening of Katsura-uri fruit, albeit with no major changes in proximate composition, with the exception of dietary fiber, and sugars. To determine the effects of Katsura-uri juice, the blood glucose levels of ten diabetic volunteers aged 46-75 y were monitored after its consumption, and compared with after consumption of muskmelon juice equivalent to the total weight of Katsura-uri juice. The blood glucose area under the curve level was significantly lower after consumption of Katsura-uri juice (16±5 h • mg/dL) than after consumption of muskmelon juice (55±17 h • mg/dL; p<0.05). The level of the glucose spike was also significantly lower after consumption of Katsura-uri juice (22±5 mg/dL) than after consumption of muskmelon juice (64±6 mg/dL; p<0.05). The completely ripe Katsura-uri fruit provides the best results for diabetic subjects, which is the first case of fruits sweetened with the addition of zero-calorie sweeteners.

Toxic effects of 4-methylthio-3-butenyl isothiocyanate (Raphasatin) in the rat urinary bladder without genotoxicity.

We recently reported that 4-methylthio-3-butenyl isothiocyanate (MTBITC) exerts chemopreventive effects on the rat esophageal carcinogenesis model at a low dose of 80 ppm in a diet. In contrast, some isothiocyanates (ITCs) have been reported to cause toxic effects, promotion activity, and/or carcinogenic potential in the urinary bladder of rats. In the present study, we investigated whether MTBITC had toxic effects in the urinary bladder similar to other ITCs, such as phenethyl ITC (PEITC). First, to examine the early toxicity of MTBITC, rats were fed a diet supplemented with 100, 300 or 1000 ppm MTBITC for 14 days. Treatment with 1000 ppm MTBITC caused increased organ weights and histopathological changes in the urinary bladder, producing lesions similar to those of 1000 ppm PEITC. In contrast, rats treated with 100 or 300 ppm MTBITC showed no signs of toxicity. Additionally, we performed in vivo genotoxicity studies to clarify whether MTBITC may exhibit a carcinogenic potential through a genotoxic mechanism in rats. Rats were treated with MTBITC for 3 days at doses of 10, 30 or 90 mg kg-1 body weight by gavage, and comet assays in the urinary bladder and micronucleus assays in the bone marrow were performed. No genotoxic changes were observed after treatment with MTBITC at all doses. Overall, these results suggested that the effects of MTBITC in the rat urinary bladder are less than those of PEITC, but that MTBITC could have toxic effects through a nongenotoxic mechanism in the urinary bladder of rats at high doses. Copyright © 2016 John Wiley & Sons, Ltd.