Effects of palmitoyl-KVK-L-ascorbic acid on skin wrinkles and pigmentation.

Wrinkle formation and abnormal pigmentation are major clinical alterations associated with skin aging. As the aim of our study was to investigate the effects of palmitoyl-KVK-L-ascorbic acid on skin aging, the anti-wrinkle and depigmentation effects of palmitoyl-KVK-L-ascorbic acid were evaluated by measuring collagen expression in dermal fibroblast cells and inhibition of melanogenesis in B16F1 cells, respectively. The anti-aging effect of palmitoyl-KVK-L-ascorbic acid cream was also evaluated against a placebo cream in a clinical trial. Our results confirmed that the expression of type Ι collagen in dermal fibroblast cells treated with palmitoyl-KVK-L-ascorbic acid (0.1-4 µg/mL) increased in a dose-dependent manner. In B16F1 cells, treatment with 20 µg/mL palmitoyl-KVK-L-ascorbic acid reduced the melanin content by approximately 20% compared to alpha-melanocyte stimulating hormone treatment. In the clinical trial, application of palmitoyl-KVK-L-ascorbic acid cream led to an improvement in skin roughness and lightness in 12 and 8 weeks, respectively. Our data show that palmitoyl-KVK-L-ascorbic acid is an effective anti-aging agent that reduces wrinkles and abnormal skin pigmentation.

Megestrol Acetate Increases the Proliferation, Migration, and Adipogenic Differentiation of Adipose-Derived Stem Cells via Glucocorticoid Receptor.

UNLABELLED: : Because adipose-derived stem cells (ASCs) are usually expanded to acquire large numbers of cells for therapeutic applications, it is important to increase the production yield and regenerative potential during expansion. Therefore, a tremendous need exists for alternative ASC stimuli during cultivation to increase the proliferation and adipogenic differentiation of ASCs. The present study primarily investigated the involvement of megestrol acetate (MA), a progesterone analog, in the stimulation of ASCs, and identifies the target receptors underlying stimulation. Mitogenic and adipogenic effects of MA were investigated in vitro, and pharmacological inhibition and small interfering (si) RNA techniques were used to identify the molecular mechanisms involved in the MA-induced stimulation of ASCs. MA significantly increased the proliferation, migration, and adipogenic differentiation of ASCs in a dose-dependent manner. Glucocorticoid receptor (GR) is highly expressed compared with other nuclear receptors in ASCs, and this receptor is phosphorylated after MA treatment. MA also upregulated genes downstream of GR in ASCs, including ANGPTL4, DUSP1, ERRF11, FKBP5, GLUL, and TSC22D3. RU486, a pharmacological inhibitor of GR, and transfection of siGR significantly attenuated MA-induced proliferation, migration, and adipogenic differentiation of ASCs. Although the adipogenic differentiation potential of MA was inferior to that of dexamethasone, MA had mitogenic effects in ASCs. Collectively, these results indicate that MA increases the proliferation, migration, and adipogenic differentiation of ASCs via GR phosphorylation. SIGNIFICANCE: Magestrol acetate (MA) increases the proliferation, migration, and adipogenic differentiation of adipose-derived stem cells (ASCs) via glucocorticoid receptor phosphorylation. Therefore, MA can be applied to increase the production yield during expansion and can be used to facilitate adipogenic differentiation of ASCs.

Korean mistletoe (Viscum album coloratum) extract extends the lifespan of nematodes and fruit flies.

Viscum album coloratum (Korean mistletoe) is a semi-parasitic plant that grows on various trees and has a variety of biological functions such as immunomodulation, apoptosis, and anti-tumor activity. In this study, we investigated the effects of Korean mistletoe extract (KME) on lifespan in experimental models using Caenorhabditis elegans and Drosophila melanogaster. Supplementation of KME at 50 µg/ml extended the mean survival time by 9.61 and 19.86 % in worms and flies, respectively. The longevity benefit of KME was not due to reduced feeding, reproduction, and/or locomotion in flies and worms. The supplementation of KME also did not increase resistance to various stresses including heat shock, oxidative, or starvation stresses. Furthermore, KME did not further extend the lifespan of flies fed a dietary restricted diet but did increase the expression of Sir2, one of the target genes of dietary restriction, suggesting that KME may function as a putative dietary restriction mimetic. These results also suggest that the longevity promoting effects of KME may be an example of mild stress-induced hormesis.

Korean mistletoe (Viscum album coloratum) extract improves endurance capacity in mice by stimulating mitochondrial activity.

The beneficial effects of exercise on overall health make it desirable to identify the orally active agents that enhance the effects of exercise in an effort to cure metabolic diseases. Natural compounds such as resveratrol (RSV) are known to increase endurance by potentiating mitochondrial function. Korean mistletoe (Viscum album coloratum) extract (KME) has characteristics similar to those of RSV. In the present study, we determined whether KME could increase mitochondrial activity and exert an anti-fatigue effect. We found that KME treatment significantly increased the mitochondrial oxygen consumption rate (OCR) in L6 cells and increased the expression of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and silent mating type information regulation 2 homolog 1 (SIRT1), two major regulators of mitochondria function, in C2C12 cells. In the treadmill test, KME-treated mice could run 2.5-times longer than chow-fed control mice. Additionally, plasma lactate levels of exhausted mice were significantly lower in the KME-treated group. In addition, the swimming time to exhaustion of mice treated with KME was prolonged by as much as 212% in the forced-swim test. Liver and kidney histology was similar between the KME-treated and phosphate-buffered saline-treated animals, indicating that KME was nontoxic. Taken together, our data show that KME induces mitochondrial activity, possibly by activating PGC-1α and SIRT1, and improves the endurance of mice, strongly suggesting that KME has great potential as a novel mitochondria-activating agent.