Monodemethylated Metabolites of Orally Administered Nobiletin: Identification and Quantitation in Rat Plasma and Tissues.

Although nobiletin (Nob) is a promising functional food component in view of its multifaceted physiological activity, the metabolism of this flavonoid remains underexplored. Herein, we examine the pharmacokinetics and tissue distribution of orally ingested Nob in rats, focusing on the six monodemethylnobiletin (MDNob) isomers as the main Nob metabolites. Two of these metabolites, namely, 6-MDNob and 8-MDNob, are chemically prepared for the first time, and a method for the simultaneous determination of all six MDNobs is developed. The obtained results demonstrate the production of 8-MDNob as a novel Nob metabolite and confirm the previously reported generation of 6-MDNob and 7-MDNob as oral metabolites of Nob in vivo. Finally, a quantitative relationship is established between the amount of metabolically generated MDNobs and that of administered Nob. Thus, this work paves the way for the broad applications and safe usage of Nob.

In Utero Exposure to Di( n-butyl)phthalate Induces Morphological and Biochemical Changes in Rats Postpuberty.

Pregnant Sprague-Dawley rats were orally administered di( n-butyl)phthalate (DBP; 100 mg/kg/day) on gestation days (GD) 12 to 21. We investigated the male offspring and probed morphological alterations in Sertoli cells at 7, 9, 14, and 17 weeks of age. Parameters assessed in this study included offspring number, sex ratios, body weights, testis weights, seminiferous tubule (ST) profile numbers and diameters, number of vimentin-labeled Sertoli cells, and both testosterone and follicle-stimulating hormone (FSH) levels. Testicular weight/body weight ratios and the numbers and diameters of ST in maximum transverse testicular sections were statistically similar at weeks 7 and 9; however, at weeks 14 and 17, they were statistically different and displayed higher BrdU-positive Sertoli cells/Sertoli cell ratios in the DBP treatment group. Noteworthily, the serum FSH levels were higher and testicular testosterone levels were lower in the DBP treatment group. To our knowledge, the present study is the first to report that in utero DBP exposure significantly increased Sertoli cell numbers and their cellular proliferation from postpuberty to adulthood, with a significant decrease in testicular testosterone and an increase in FSH.

C(35)-terpenes from Bacillus subtilis KSM 6-10.

Four C(35)-terpenes (1-4) were isolated from a liquid culture of Bacillus subtilis KSM 6-10. Compounds 1 and 2, tetraprenyl-beta-curcumene and tetraprenyl-alpha-curcumene, respectively, were previously isolated from a spore preparation of the same species, whereas 3 and 4 are new C(35)-terpenols. The C(35)-terpenols (3 and 4) possess polycyclic skeletons. We propose that the C(35)-terpenols (3 and 4) are formed by cyclization of the acyclic C(35)-terpenes (1 and 2). Because only trace amounts of C(35)-terpenols 3 and 4 were found in the spore in contrast to the vegetative cells of B. subtilis KSM 6-10, it is assumed that the expression of terpene cyclase is not related to sporulation, as has been observed by other researchers in a different strain.