Eri Matsubara

Inhibitory components from the buds of clove (Syzygium aromaticum) on melanin formation in B16 melanoma cells

In the course to find a new whitening agent, we evaluated the methanol extract from bud of clove (Syzygium aromaticum) on melanin formation in B16 melanoma cells. Eugenol and eugenol acetate were isolated as the active compounds and showed melanin inhibition of 60% and 40% in B16 melanoma cell with less cytotoxicity at the concentration of 100 and 200 μg/mL, respectively. Furthermore, an essential oil prepared from the bud of clove, which contain eugenol and eugenol acetate as dominant components, showed melanin inhibition of 50% and 80% in B16 melanoma cells at the concentration of 100 and 200 μg/mL, respectively.

GLI1, a crucial mediator of sonic hedgehog signaling in prostate cancer, functions as a negative modulator for androgen receptor.

Sonic hedgehog (SHH) signaling, acting in a combinatorial manner with androgen signaling, is essential for prostate patterning and development. Recently, elevated activation of SHH signaling has been shown to play important roles in proliferation, progression and metastasis of prostate cancer. In this report, we demonstrate for the first time, that GLI1, which has been shown to play a central role in SHH signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor (AR)-mediated transactivation, at least in part, by directly interacting with AR. Our observations suggest that the SHH-GLI pathway might be one of determinants governing the transition of prostate cancer from anandrogen-dependent to an androgen-independent state by compensating, or even superseding androgen signaling.

Roles for corticotropin-releasing factor receptor type 1 in energy homeostasis in mice

OBJECTIVE Expression of corticotropin-releasing factor type 1 receptor (CRFR1) has been shown on pancreatic β cells, and its activation potentiates glucose-stimulated insulin secretion (GSIS). However, the roles of CRFR1 in energy metabolism beyond insulin release remain elusive. MATERIALS/METHODS We characterized the metabolic phenotypes of mice lacking CRFR1 (CRFR1KO mice) under conditions of energy excess. RESULTS When fed a normal diet, the glucose profile of CRFR1KO mice in response to a glucose tolerance test was similar to that of wild-type (WT) mice, while serum insulin levels were significantly lower in CRFR1KO mice, reflecting high insulin sensitivity in part due to very low glucocorticoid levels. Histology of the pancreas revealed islet hypoplasia in CRFR1KO mice, suggesting a role of CRFR1 in maintaining the β cell mass in a manner similar to incretins. In response to a high-fat diet, CRFR1KO mice showed insulin resistance, but serum insulin levels during glucose challenge remained at a low level, indicating defective GSIS. In addition, CRFR1KO mice showed resistance to diet-induced obesity and hepatic steatosis. Although total food intake was not different between CRFR1KO and WT mice, oxygen consumption was significantly increased in CRFR1KO mice. The increased energy expenditure may explain the lean phenotype of CRFR1KO mice under conditions of energy excess. CONCLUSIONS Our results suggest that CRFR1 plays important roles in whole body energy homeostasis, providing compelling evidence of the close relationship between energy homeostasis and the function of the hypothalamic-pituitary-adrenal axis.

Inhalation of Japanese cedar ( Cryptomeria japonica ) wood odor causes psychological relaxation after monotonous work among female participants

Essential oils have potential to mitigate stress symptoms and treat symptoms related to mental health. Few studies have investigated the effects of wood-derived aromatics on endocrinological and psychological responses in an actual space. In this study, we evaluated the effects of essential oil derived from Japanese cedar (Cryptomeria japonica) wood on the recovery state of female participants after they performed monotonous work. We determined the levels of salivary stress markers to describe the endocrinological responses. And we also used questionnaires to assess the perception of the odor of experimental rooms and psychological states. We found that olfactory stimulation with the volatile compounds of essential oil derived from Japanese cedar wood modulates mood states, and may transiently decrease sympathetic nervous activity. We suggest that olfactory stimulation with the volatile compounds of essential oil derived from Japanese cedar wood could be useful for maintaining mental health among women.

Modulation of Androgen Receptor Transactivation by FoxH1. A Newly Identified Androgen Receptor Corepressor

Androgen signaling plays key roles in the development and progression of prostate cancer, and numerous ongoing studies focus on the regulation of androgen receptor (AR) transactivity to develop novel therapies for the treatment of androgen-independent prostate cancer. FoxH1, a member of the Forkhead-box (FOX) gene family of transcription factors, takes part in mediating transforming growth factor-beta/activin signaling through its interaction with the Smad2.Smad4 complex. Using a series of experiments, we found that FoxH1 repressed both ligand-dependent and -independent transactivation of the AR on androgen-induced promoters. This action of FoxH1 was independent of its transactivation capacity and activin A but relieved by Smad2.Smad4. In addition, the repression of the AR by FoxH1 did not require deacetylase activity. A protein-protein interaction was identified between the AR and FoxH1 independently of dihydrotestosterone. Furthermore, a confocal microscopic analysis of LNCaP cells revealed that the interaction between the AR and FoxH1 occurred in the nucleus and that FoxH1 specifically blocked the foci formation of dihydrotestosterone-activated AR, which has been shown to be correlated with the AR transactivation potential. Taken together, our results indicate that FoxH1 functions as a new corepressor of the AR. Our observations not only strengthen the role of FoxH1 in AR-mediated transactivation but also suggest that therapeutic interventions based on AR-coregulator interactions could be designed to block both androgen-dependent and -independent growth of prostate cancer.