Silibinin is a flavonolignan isolated from milk thistle (Silybum marianum). Silibinin has been reported to possess multiple biological activities; however, its effect on melanogenesis remains unclear. This study investigated the effect of silibinin on melanogenesis in melanoma cells and the associated molecular mechanism. Our findings demonstrated that silibinin markedly increased melanin content in murine B16-F1 and human HMV-II melanoma cells. Silibinin activated intracellular tyrosinase activity and expression of tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2, and microphthalmia-associated transcription factor (MITF). Furthermore, silibinin enhanced the phosphorylation of cyclic AMP-responsive element-binding protein (CREB), protein kinase A (PKA), and p38 mitogen-activated protein kinase (MAPK) but not of Akt and extracellular signal-regulated kinase (ERK). The specific PKA (H-89) and p38 (SB203580) inhibitors significantly attenuated silibinin-mediated melanin synthesis. These results suggest that silibinin is an effective stimulator of melanogenesis through upregulation of the protein expression of melanogenic enzymes activated by the PKA and p38 pathways, leading to CREB phosphorylation and MITF expression. Therefore, silibinin may have potential for use in the treatment of hypopigmentation disorders.

Bone fracture is an important trauma frequently encountered into emergency medicine as well as orthopedics reflecting an aging society. Oncostatin M, an inflammatory cytokine produced by osteal macrophages, has been considered to play a crucial role in fracture healing. Macrophage colony-stimulating factor (M-CSF) secreted from osteoblasts is essential in osteoclastgenesis, and the secretion is stimulated by transforming growth factor-β (TGF-β). The aim of this study is to elucidate the effects of oncostatin M on the TGF-β-induced M-CSF synthesis in osteoblast-like MC3T3-E1 cells and the underlying mechanisms. Oncostatin M attenuated the TGF-β-stimulated M-CSF release and the mRNA expressions. SMAD3 inhibitor SIS3, p38 MAP kinase inhibitor SB203580, MEK1/2 inhibitor PD98059, and SAPK/JNK inhibitor SP600125 significantly suppressed the M-CSF release. Oncostatin M suppressed the TGF-β-induced phosphorylation of p44/p42 MAP kinase and SAPK/JNK, but failed to affect the phosphorylation of SMAD3 and p38 MAP kinase. Oncostatin M attenuated the TGF-β-stimulated vascular endothelial growth factor (VEGF) release and the TGF-β-induced mRNA expressions of VEGF. These results strongly suggest that oncostatin M downregulates TGF-β signaling upstream of p44/p42 MAP kinase and SAPK/JNK, but not SMAD 2/3 and p38 MAP kinase, in osteoblasts, leading to the attenuation of M-CSF synthesis. Our findings might provide a new therapeutic strategy for the acceleration of fracture healing process.

Torpor, a state of lowered body temperature due to active reduction of the metabolic rate, has potential medical benefits. The aim of this study was to establish a novel laboratory animal that enter torpor without imposing complex conditions. When house musk shrews (Suncus murinus) were kept at an ambient temperature of 24°C, most of the animals did not enter daily torpor. However, when the ambient temperature was lowered to below 20°C, all of the shrews showed torpor in the absence of fasting and short-day photoperiod. The shrews that were exposed to a stepwise decrease in ambient temperature from 24°C to 8°C entered torpor even after returning them to a room kept at 24°C. In conclusion, this study indicates that Suncus murinus may be a suitable model animal for elucidating the mechanism of daily torpor. Elucidation of the mechanisms of torpor by using this model may be useful for inducing a state of artificial hibernation in various species including humans.