Perspective on Roseroot (Rhodiola rosea) studies.

Rhodiola rosea (roseroot) extract is a commercially successful product, primarily used to reduce the effect of fatigue on physical and mental performance. In this perspective we present our investigation of the most recent studies performed on human subjects. With a focus on the statistical methods we found considerable shortcomings in all but one of the studies that claim significant improvement from roseroot extract. Overall, the study designs have not been well explained. Experimental results have been confused and appear to be in some cases incorrect. Some of the conclusions are based on selected results and contradicting data have not been adequately taken into account. We point to other studies of higher quality performed on roseroot, several that found no significant effect and one that did. We conclude that the currently available evidence for the claimed effects is insufficient and that the effect of Rhodiola rosea is in need of further investigation before therapeutic claims can be made.

Localization of neuropeptide Y receptor Y5 mRNA in the guinea pig brain by in situ hybridization.

Neuropeptide Y (NPY) has prominent stimulatory effects on food intake in virtually all animals that have been studied. In mammals, the effect is primarily mediated by receptors Y1 and Y5, which seem to contribute to different aspects of feeding behavior in guinea pigs and rats/mice. Interestingly, differences in receptor distribution among mammalian species have been reported. To get a broader perspective on the role of Y5, we describe here studies of guinea pig (Cavia porcellus), a species which due to its phylogenetic position in the mammalian radiation is an interesting complement to previous studies in rat and mouse. Guinea pig brain sections were hybridized with two 35S-labeled oligonucleotides complementary to Y5 mRNA. The highest expression levels of Y5 mRNA were observed in the hippocampus and several hypothalamic and brain stem nuclei implicated in the regulation of feeding, such as the paraventricular, arcuate and ventromedial hypothalamic nuclei. This contrasts with autoradiography studies that detected low Y5-like binding in these areas, a discrepancy observed also in rat and human. Y5 mRNA expression was also seen in the striatum, in great contrast to mouse and rat. Taken together, these data show that Y5 mRNA distribution displays some interesting species differences, but that its expression in feeding centers seems to be essentially conserved among mammals, adding further support for an important role in food intake.

Pharmacological comparison of rat and human melanocortin 3 and 4 receptors in vitro.

The melanocortin 3 and 4 receptors are G-protein-coupled receptors found in the hypothalamus with important role in regulation of the energy balance. In this study, we performed pharmacological comparison of the rat and human melancortin (MC) 3 and MC4 receptors. We transiently expressed the genes for these receptors individually in a mammalian cell line and determined the binding affinities to several MSH peptides. The results showed no major difference between the rat and human MC3 receptors while the rat MC4 receptor had higher affinity to several peptides compared with the human MC4 receptor. NDP-, alpha-, beta-, gamma-MSH, ACTH(1-24), HS014 and MTII had from 5- to 34-fold higher affinity for the rat MC4 receptor, while SHU9119, HS024 and HS028 had similar affinity for both the MC4 receptors. Pharmacological species difference have earlier been reported for the MC1 and MC5 receptors but this is the first report showing important differences between the rat and human MC4 receptors.

Neuropeptide Y inhibits the biosynthesis of sulfated neurosteroids in the hypothalamus through activation of Y(1) receptors.

We have recently shown that hydroxysteroid sulfotransferase (HST), the enzyme responsible for the biosynthesis of pregnenolone sulfate (Delta(5)PS) and dehydroepiandrosterone sulfate (DHEAS), is expressed in neurons located in the anterior preoptic area and the dorsal magnocellular nucleus of the frog diencephalon. As these two nuclei are richly innervated by NPY-immunoreactive fibers, we investigated the possible implication of NPY in the control of Delta(5)PS and DHEAS biosynthesis. Double labeling of frog brain sections revealed that 42% of the HST-immunoreactive perikarya in the diencephalon were contacted by NPY-containing fibers. In situ hybridization studies showed that Y(1) and Y(5) receptor mRNAs are expressed in the anterior preoptic area and the dorsal magnocellular nucleus. Pulse-chase experiments with (35)S-labeled 3'-phosphoadenosine 5'-phosphosulfate as a sulfate donor demonstrated that frog NPY (fNPY) inhibited the conversion of [(3)H]Delta(5)P and [(3)H]dehydroepiandrosterone ([(3)H]DHEA) into [(3)H,(35)S]Delta(5)PS and [(3)H,(35)S]DHEAS by diencephalic explants. The inhibitory effect of fNPY on Delta(5)PS and DHEAS formation was mimicked by (pPYY) and [Leu(31),Pro(34)]pNPY, which is an agonist for non-Y(2) receptors in mammals, and was completely suppressed by the Y(1) receptor antagonist BIBP3226. Conversely, the Y(2) receptor agonist pNPY-(13-36) and the Y(5) receptor agonist [D-Trp(32)]pNPY did not significantly modify the biosynthesis of [(3)H,(35)S]Delta(5)PS and [(3)H,(35)S]DHEAS. The present study provides the first evidence for the innervation of neurosteroid-producing neurons by NPY fibers. Our data also demonstrate that NPY, acting via Y(1) receptors, exerts an inhibitory effect on the biosynthesis of sulfated neurosteroids.