Quercetin 3-O-Galactoside Isolated from Limonium tetragonum Inhibits Melanogenesis by Regulating PKA/MITF Signaling and ERK Activation.

Quercetin 3-O-galactoside (Q3G) is a common dietary flavanol that has been shown to possess several bioactivities, including anti-melanogenesis. However, how Q3G exerts its anti-melanogenic effect has not been studied. The current study, therefore aimed to investigate the anti-melanogenesis potential of Q3G and elucidate the underlying action mechanism in α-melanocyte-stimulating hormone (α-MSH)-induced hyperpigmentation model of B16F10 murine melanoma cells. Results showed that α-MSH stimulation significantly increased tyrosinase (TYR) and melanin production, which were significantly downregulated by Q3G treatment. The treatment with Q3G suppressed the transcriptional and protein expressions of melanogenesis-related enzymes TYR, tyrosinase related protein-1 (TRP-1), and TRP-2, along with the melanogenic transcription factor microphthalmia-associated transcription factor (MITF) in B16F10 cells. It was shown that Q3G downregulated MITF expression and suppressed its transcriptional activity by inhibiting the cAMP-dependent protein kinase A (PKA)-mediated activation of CREB and GSK3ß. In addition, MAPK-regulated MITF activation signaling was also involved in the inhibition of melanin production by Q3G. The results suggest that the anti-melanogenic properties of Q3G rationalize further studies in vivo to confirm its action mechanism and consequent utilization as a cosmetic ingredient against hyperpigmentation.

Dracunculin Inhibits Adipogenesis in Human Bone Marrow-Derived Mesenchymal Stromal Cells by Activating AMPK and Wnt/ß-Catenin Signaling.

Increased bone marrow adiposity is widely observed in patients with obesity and osteoporosis and reported to have deleterious effects on bone formation. Dracunculin (DCC) is a coumarin isolated from Artemisia spp. but, until now, has not been studied for its bioactive potential except antitrypanosomal activity. In this context, current study has reported the anti-adipogenic effect of DCC in human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). DCC dose-dependently inhibited the lipid accumulation and expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) in hBM-MSCs induced to undergo adipogenesis. To elucidate its action mechanism, the effect of DCC on Wnt/ß-catenin and AMPK pathways was examined. Results showed that DCC treatment activated Wnt/ß-catenin signaling pathway via AMPK evidenced by increased levels of AMPK phosphorylation and Wnt10b expression after DCC treatment. In addition, DCC treated adipo-induced hBM-MSCs exhibited significantly increased nuclear levels of ß-catenin compared with diminished nuclear PPARγ levels. In conclusion, DCC was shown to be able to hinder adipogenesis by activating the ß-catenin via AMPK, providing potential utilization of DCC as a nutraceutical against bone marrow adiposity.

Bypass surgery versus medical treatment for symptomatic moyamoya disease in adults.

OBJECTIVE In this study the authors evaluated whether extracranial-intracranial bypass surgery can prevent stroke occurrence and decrease mortality in adult patients with symptomatic moyamoya disease (MMD). METHODS The medical records of 249 consecutive adult patients with symptomatic MMD that was confirmed by digital subtraction angiography between 2002 and 2011 at 8 institutions were retrospectively reviewed. The study outcomes of stroke recurrence as a primary event and death during the 6-year follow-up and perioperative complications within 30 days as secondary events were compared between the bypass and medical treatment groups. RESULTS The bypass group comprised 158 (63.5%) patients, and the medical treatment group comprised 91 (36.5%) patients. For 249 adult patients with MMD, bypass surgery showed an HR of 0.48 (95% CI 0.27-0.86, p = 0.014) for stroke recurrence calculated by Cox regression analysis. However, for the 153 patients with ischemic MMD, the HR of bypass surgery for stroke recurrence was 1.07 (95% CI 0.43-2.66, p = 0.887). For the 96 patients with hemorrhagic MMD, the multivariable adjusted HR of bypass surgery for stroke recurrence was 0.18 (95% CI 0.06-0.49, p = 0.001). For the treatment modality, indirect bypass and direct bypass (or combined bypass) did not show any significant difference for stroke recurrence, perioperative stroke, or mortality (log rank; p = 0.524, p = 0.828, and p = 0.616, respectively). CONCLUSIONS During the treatment of symptomatic MMD in adults, bypass surgery reduces stroke recurrence for the hemorrhagic type, but it does not do so for the ischemic type. The best choice of bypass methods in adult patients with MMD is uncertain. In adult ischemic MMD, a prospective randomized study to evaluate the effectiveness and safety of bypass surgery to prevent recurrent stroke is necessary.