The effects of centipedegrass extract on hair growth via promotion of anagen inductive activity.

To investigate the CGE on hair growth and to explore the mechanism that is involved in the acceleration of anagen induction, we investigated the effects of CGE studied on cell proliferation and molecular mechanism in human hair dermal papilla cells (hDPCs) and keratinocytes (HaCaT cells). Additionally, hair growth evaluation was carried out following topical treatment of the dorsal skin of telogen C57BL/6 mice with CGE for 14 days. As result, CGE increased cell viability and ALP activity in hDPCs. Moreover, CGE increased the expression of catenin beta 1 (CTNNB1), ALP, sex-determining region Y-box 2 (SOX2), insulin-like growth factor 1 (IGF1), and vascular endothelial growth factor A (VEGFA) genes in hDPCs. CGE increased the expression of proteins such as ALP, ß-catenin, and phosphorylation of glycogen synthase kinase 3ß (pGSK3ß), and protein kinase B (pAKT) in hDPCs. Furthermore, CGE induced the proliferation of HaCaT cells and up-regulated AKT-ERK-GSKß-ß-catenin signaling in HaCaT cells. Additionally, the anagen induction effects of CGE were confirmed on the telogen-anagen transition mice model. these findings demonstrated that CGE promoted the entering the growth phase of hair follicle via activation of ß-catenin signaling pathways in vivo. Thus, this study suggests that CGE might be a potential therapeutic reagent for hair growth.

Centipedegrass extract enhances radiosensitivity in melanoma cells by inducing G2/M cell cycle phase arrest.

Melanoma is aggressive, highly metastatic, and potentially fatal. In the case of patients with advanced melanoma, it is difficult to expect a good prognosis, since this cancer has low sensitivity to chemotherapy and radiation therapy. The use of natural ingredients may enhance existing therapies. Centipedegrass extract (CGE) which contains phenolic structures and C-glycosyl flavones, has been shown to have anti-inflammatory effects and anti-cancer effects. The purpose of this study was to evaluate the radio sensitizing effects of CGE in combination with ionizing radiation (IR). Two melanoma cell lines were exposed to IR after treatment with CGE at concentrations that were not toxic alone. The effects of CGE + IR on cell survival, cell cycle, and apoptotic cell death were examined using MTT and Muse® Cell Analyzer, and fluorescence microscopy. Molecular signaling mechanisms were explored by western blots. Our findings showed that co-treatment of CGE + IR reduced the survival of melanoma cells more than IR alone. Also, cell cycle arrest in CGE-treated cells was enhanced and these cells became more radiosensitive. CGE + IR increased apoptotic cell death more than IR alone. Western blot results showed that the effect of CGE + IR involved MAPKs (ERK1/2, p38, and JNK) pathway. Our study suggests that CGE + IR treatment enhanced radio-sensitization and cell death of melanoma cells via cell cycle arrest and the MAPKs pathway.

Boehmite enhances hair follicle growth via stimulation of dermal papilla cells by upregulating ß-catenin signalling.

Hair growth, a complex process, has long been the subject of intense research. Recent developments in material technology have revealed boehmite as a new therapeutic modality for use in wound healing and scar reduction, indicating its beneficial effects. Nonetheless, the biological bases of the beneficial effects of boehmite remain unknown. We investigated the hair growth properties of boehmite in vitro and in vivo and observed dose-dependent proliferation of human dermal papilla cells (hDPCs) in vitro and hair regrowth in a mouse model. To investigate the effects of boehmite on the promotion of cell transition to the anagen phase, we evaluated hDPC viability, alkaline phosphatase (ALP) activity, protein expression and vascular endothelial growth factor (VEGF) secretion in vitro and assessed the anagen-promoting effects of boehmite via gross observation and histological analysis in a mouse model. Boehmite increased hDPC viability, ALP activity, AKT/GSK3ß/ß-catenin pathway activity, anagen-related gene expression and VEGF secretion; moreover, it accelerated hair regrowth in a catagen-anagen transition model via upregulation of ß-catenin signalling and follicular cell proliferation. Collectively, our results indicate that boehmite accelerates hair growth, partly via its effects on critical events in the active phase of the hair follicle cycle, including the promotion of the proliferation of hDPCs and their immediate progeny to the follicle base.

Therapeutic potential of topically administered γ-AlOOH on 2,4-dinitrochlorobenzene-induced atopic dermatitis-like lesions in Balb/c mice.

Boehmite (γ-AlOOH) has a wide range of applications in a variety of industrial and biological fields. However, little is known about its potential roles in skin diseases. The current study investigated its effect on atopic dermatitis (AD). Following characterization, cytotoxicity, pro-inflammatory response and oxidative stress associated with boehmite were assessed, using TNF-α-induced keratinocytes and mast cells. In addition, therapeutic effects of boehmite, topically administered to Balb/c mice induced by 2,4-dinitrochlorobenzene (DNCB), were evaluated. Expression of cytokines (TLSP, IL-25 and IL-33) and the generation of ROS from keratinocytes induced by TNF-α were significantly inhibited by boehmite without affecting cell viability. MAPKs (ERK, JNK and p38) required for cytokine expression were suppressed by boehmite treatment. Up-regulation of cytokines (TSLP, IL-4, IL-5, IL-13, RANTES) in human mast cells treated with phorbol 12-myristate 13-acetate and calcium ionophore was also suppressed by boehmite. Boehmite improved the AD severity score, epidermal hyperplasia and transepidermal water loss in DNCB-induced AD-like lesions. Moreover, Th2-mediated cytokine expression, mast cell hyperplasia and destruction of the skin barrier were improved by boehmite treatment. Overall, we demonstrated that boehmite may potentially protect against AD.

Effects on skin of Stichopus japonicus viscera extracts detected with saponin including Holothurin A: Down-regulation of melanin synthesis and up-regulation of neocollagenesis mediated by ERK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Stichopus japonicus (sea cucumber), edible traditional food in Asia, and its extracts are renowned for their wound healing, pain relieving, and cosmetic effects in traditional medicine. Holothurins, toxins isolated from sea cucumber, are thought to be active components for their beneficial effects. However, researchers have yet to outline specific mechanisms thereof. AIM OF THE STUDY: The present study was designed to evaluate the anti-melanogenic and anti-wrinkle properties of S. japonicus viscera extracts (VF) on the skin via in vitro and ex vivo experiments and to assess the anti-aging effects of S. japonicus viscera extracts in relation to known wound healing and cosmetic processes. MATERIALS AND METHODS: The viscera of live S. japonicus specimens were freeze dried and ground into a powder. Aqueous extracts were subsequently prepared from the concentrated powder using a water extraction method. To investigate the inhibitory effects of VF on melanogenesis, mushroom tyrosinase activity assay and melanin assay were performed on Melan-A cells. To further delineate the anti-melanogenic properties of VF, western blot analysis for tyrosinase, TRP-1, TRP-2, MITF, and ERK was conducted. Changes in collagen synthesis in human dermal fibroblast (HDF) were evaluated via CCK-8 assay and immunocytochemistry to determine the anti-wrinkle effects of VF. Finally, anti-aging properties were examined in a human skin equivalent ex vivo model. RESULTS: In Melan-A cells, VF treatment reduced melanin contents in a concentration-dependent manner. The anti-melanogenic effects of VF appeared to be due to enzymatic inhibition of tyrosinase. In CCK-8 assay, VF also significantly increased the viability of HDFs in a concentration-dependent manner. Immunoblot analysis revealed phosphorylation of ERK in HDFs treated with VF. In a human skin equivalent ex vivo model (Neoderm®-ED), VF treatment at a concentration of 50 µg/ml enhanced collagen type IV and Ki-67 expression and downregulated MMP-9 expression. CONCLUSION: This study demonstrated that aqueous extracts from S. japonicus viscera are effective whitening and anti-aging agents that stimulate ERK signaling to inhibit melanin synthesis and promote collagen synthesis.

Neuroprotective effects of 20(S)-protopanaxadiol against glutamate-induced mitochondrial dysfunction in PC12 cells.

Ginseng (Panax ginseng C.A. Mey.) is commonly used in traditional oriental medicine for its wide spectrum of medicinal properties, including anti-inflammatory, antitumorigenic, adaptogenic and anti-aging properties. 20(S)-Protopanaxadiol (PPD), the main intestinal metabolite of ginsenosides, is one of the active ingredients in ginseng. In this study, we aimed to investigate the neuroprotective effects of PPD on PC12 cells; however, the underlying mechanisms remain elusive. We examined cell viability by MTT assay and the morphological changes of PC12 cells following glutamate­induced cell damage and evaluated the anti­apoptotic effects of PPD using Hoechst 33258 staining, western blot analysis and Muse™ Cell Analyzer and the antioxidant effects of PPD using FACS analysis and immunofluorescence. Furthermore, PPD exerted protective effects on PC12 cells via the inhibition of mitochondrial damage against glutamate-induced excitotoxicity using immunofluorescence, electron microscopy and FACS analysis. We demonstrate that treatment with PPD suppresses apoptosis, which contributes to the neuroprotective effects of PPD against glutamate­induced excitotoxicity in PC12 cells. Treatment with PPD inhibited nuclear condensation and decreased the number of Annexin V-positive cells. In addition, PPD increased antioxidant activity and mitochondrial homeostasis in the glutamate-exposed cells. These antioxidant effects were responsible for the neuroprotection and enhanced mitochondrial function following treatment with PPD. Furthermore, PD inhibited the glutamate-induced morphological changes in the mitochondria and scavenged the mitochondrial and cytosolic reactive oxygen species (ROS) induced by glutamate. In addition, mitochondrial function was significantly improved in terms of mitochondrial membrane potential (MMP) and enhanced mitochondrial mass compared with the cells exposed to glutamate and not treated with PPD. Taken together, the findings of our study indicate that the antioxidant effects and the enhanced mitochondrial function triggered by PPD contribute to the inhibition of apoptosis, thus leading to a neuroprotective response, as a novel survival mechanism.