Human Umbilical Cord Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Reduce Skin Inflammation In Vitro.

The protective roles of extracellular vesicles derived from human umbilical cord mesenchymal stem cells against oxazolone-induced damage in the immortalized human keratinocyte cell line HaCaT were investigated. The cells were pretreated with or without UCMSC-derived extracellular vesicles 24 h before oxazolone exposure. The pretreated UVMSC-EVs showed protective activity, elevating cell viability, reducing intracellular ROS, and reducing the changes in the mitochondrial membrane potential compared to the cells with a direct oxazolone treatment alone. The UCMSC-EVs exhibited anti-inflammatory activity via reducing the inflammatory cytokines IL-1ß and TNF-α. A mechanism study showed that the UCMSC-EVs increased the protein expression levels of SIRT1 and P53 and reduced P65 protein expression. It was concluded that UVMSC-EVs can induce the antioxidant defense systems of HaCaT cells and that they may have potential as functional ingredients in anti-aging cosmetics for skin care.

Nicotinamide Mononucleotide and Coenzyme Q10 Protects Fibroblast Senescence Induced by Particulate Matter Preconditioned Mast Cells.

Particulate matter (PM) pollutants impose a certain degree of destruction and toxicity to the skin. Mast cells in the skin dermis could be activated by PMs that diffuse across the blood vessel after being inhaled. Mast cell degranulation in the dermis provides a kind of inflammatory insult to local fibroblasts. In this study, we evaluated human dermal fibroblast responses to conditioned medium from KU812 cells primed with PM. We found that PM promoted the production of proinflammatory cytokines in mast cells and that the cell secretome induced reactive oxygen species and mitochondrial reactive oxygen species production in dermal fibroblasts. Nicotinamide mononucleotide or coenzyme Q10 alleviated the generation of excessive ROS and mitochondrial ROS induced by the conditioned medium from PM-activated KU812 cells. PM-conditioned medium treatment increased the NF-κB expression in dermal fibroblasts, whereas NMN or Q10 inhibited p65 upregulation by PM. The reduced sirtuin 1 (SIRT 1) and nuclear factor erythroid 2-related Factor 2 (Nrf2) expression induced by PM-conditioned medium was reversed by NMN or Q10 in HDFs. Moreover, NMN or Q10 attenuated the expression of senescent ß-galactosidase induced by PM-conditioned KU812 cell medium. These findings suggest that NMN or Q10 ameliorates PM-induced inflammation by improving the cellular oxidative status, suppressing proinflammatory NF-κB, and promoting the levels of the antioxidant and anti-inflammatory regulators Nrf2 and SIRT1 in HDFs. The present observations help to understand the factors that affect HDFs in the dermal microenvironment and the therapeutic role of NMN and Q10 as suppressors of skin aging.

IgE-Induced Mast Cell Activation Is Suppressed by Dihydromyricetin through the Inhibition of NF-κB Signaling Pathway.

Mast cells play a crucial role in the pathogenesis of type 1 allergic reactions by binding to IgE and allergen complexes and initiating the degranulation process, releasing pro-inflammatory mediators. Recently, research has focused on finding a stable and effective anti-allergy compound to prevent or treat anaphylaxis. Dihydromyricetin (DHM) is a flavonoid compound with several pharmacological properties, including free radical scavenging, antithrombotic, anticancer, and anti-inflammatory activities. In this study, we investigated the anti-allergic inflammatory effects and the underlying molecular mechanism of DHM in the DNP-IgE-sensitized human mast cell line, KU812. The cytokine levels and mast cell degranulation assays were determined by enzyme-linked immunosorbent assay (ELISA). The possible mechanism of the DHM-mediated anti-allergic signaling pathway was analyzed by western blotting. It was found that treatment with DHM suppressed the levels of inflammatory cytokines TNF-α and IL-6 in DNP-IgE-sensitized KU812 cells. The anti-allergic inflammatory properties of DHM were mediated by inhibition of NF-κB activation. In addition, DHM suppressed the phosphorylation of signal transducer and activator of transcription 5 (STAT5) and mast cell-derived tryptase production. Our study shows that DHM could mitigate mast cell activation in allergic diseases.

Investigation of the Anti-Melanogenic and Antioxidant Characteristics of Eucalyptus camaldulensis Flower Essential Oil and Determination of Its Chemical Composition.

The effects of essential oil from Eucalyptus camaldulensis flowers oil on melanogenesis and the oil's antioxidant characteristics were investigated. Assays of mushroom and cellular tyrosinase activities and melanin content of mouse melanoma cells were performed spectrophotometrically, and the expression of melanogenesis-related proteins was determined by Western blotting. The possible signaling pathways involved in essential oil-mediated depigmentation were also investigated using specific protein kinase inhibitors. The results revealed that E. camaldulensis flower essential oil effectively suppresses intracellular tyrosinase activity and decreases melanin amount in B16F10 mouse melanoma cells. The essential oil also exhibits antioxidant properties and effectively decreases intracellular reactive oxygen species (ROS) levels. The volatile chemical composition of the essential oil was analyzed with gas chromatography-mass spectrometry (GC/MS). The chemical constituents in the essential oil are predominately oxygenated monoterpenes (34.9%), followed by oxygenated sesquiterpenes (31.8%), monoterpene hydrocarbons (29.0%) and sesquiterpene hydrocarbons (4.3%). Our results indicated that E. camaldulensis flower essential oil inhibits melanogenesis through its antioxidant properties and by down-regulating both mitogen-activated protein kinases (MAPK) and protein kinase A (PKA) signaling pathways. The present study indicates that the essential oil has the potential to be developed into a skin care product.

Supercritical fluid extract of Lycium chinense Miller root inhibition of melanin production and its potential mechanisms of action.

BACKGROUND: The mode of action of Lycium chinense Miller root extract in skin care has never been explored. In the present study, Lycium chinense Miller root was extracted by the supercritical fluid CO2 extraction method. METHODS: In the present study, the components of the root extract were analyzed by HPLC. The effects of the extract on tyrosinase activity and melanin content were determined spectrophotometrically; the expression of melanogenesis-related proteins was determined by Western blotting; the possible signaling pathways involved in the root extract-mediated depigmentation were also investigated using specific inhibitors. RESULTS: The results revealed that the SFE of Lycium chinense Miller root (2.37-7.11 mg/mL) effectively suppressed intracellular tyrosinase activity and decreased the melanin content in B16F10 cells. The root extract also effectively decreased intracellular reactive oxygen species (ROS) levels. Furthermore, the root extract decreased the expression of melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase and tyrosinase-related protein-1 (TRP-1) and then inhibited melanogenesis in B16F10 cells. The root extract also showed antioxidant capacities and depleted cellular ROS. CONCLUSIONS: Our results indicate that the SFE of Lycium chinense Miller root inhibited melanogenesis in B16F10 cells by down-regulation of both mitogen-activated protein kinases (MAPK) and protein kinase A (PKA) signaling pathways or through its antioxidant properties.

Inhibitory effects of adlay extract on melanin production and cellular oxygen stress in B16F10 melanoma cells.

The aim of this study was to determine the effects of adlay extract on melanin production and the antioxidant characteristics of the extract. The seeds were extracted by the supercritical fluid CO2 extraction (SFE) method. The effect of adlay extract on melanin production was evaluated using mushroom tyrosinase activity assay, intracellular tyrosinase activity, antioxidant properties and melanin content. Those assays were performed spectrophotometrically. In addition, the expression of melanogenesis-related proteins was determined by western blotting. The results revealed that the adlay extract suppressed intracellular tyrosinase activity and decreased the amount of melanin in B16F10 cells. The adlay extract decreased the expression of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase related protein-1 (TRP-1) and tyrosinase related protein-2 (TRP-2). The extract also exhibited antioxidant characteristics such as free radical scavenging capacity and reducing power. It effectively decreased intracellular reactive oxygen species (ROS) levels in B16F10 cells. We concluded that the adlay extract inhibits melanin production by down-regulation of MITF, tyrosinase, TRP-1 and TRP-2. The antioxidant properties of the extract may also contribute to the inhibition of melanogenesis. The adlay extract can therefore be applied as an inhibitor of melanogenesis and could also act as a natural antioxidant in skin care products.

[8]-Gingerol inhibits melanogenesis in murine melanoma cells through down-regulation of the MAPK and PKA signal pathways.

[8]-Gingerol is an active component of Zinger and shows several pharmacological activities, such as antipyretic and anti-inflammation characteristics. To identify a potential skin-whitening agent, the inhibitory effects of [8]-gingerol on melanogenesis and its mechanism of action were investigated. In the present study, the effects of [8]-gingerol on mushroom tyrosinase, tyrosinase activity and melanin content were determined spectrophotometrically; the expression of melanogenesis-related proteins in B16F10 and B16F1 melanoma cells were determined by Western blotting. Furthermore, the possible signaling pathways involved in [8]-gingerol-mediated depigmentation were also investigated using specific inhibitors. The results revealed that [8]-gingerol (5-100µM) effectively suppressed intracellular tyrosinase activity and decreased the amount of melanin in B16F10 and B16F1 cells. In addition, [8]-gingerol also effectively decreased intracellular reactive species (RS) and reactive oxygen species (ROS) levels at the same dose range. Our results indicated that [8]-gingerol inhibited melanogenesis in B16F10 and B16F1 cells by down-regulation of both mitogen-activated protein kinases (MAPK) and protein kinase A (PKA) signaling pathways or through its antioxidant properties. Hence, [8]-gingerol could be used as an effective skin-whitening agent.

Dextromethorphan attenuates LPS-induced adhesion molecule expression in human endothelial cells.

OBJECTIVE: This study examines the effect of Dextromethorphan (d-3-methoxy-17-methylmorphinan; DXM), a commonly used cough-suppressing drug, on the expression of VCAM-1 and ICAM-1 in human umbilical vein endothelial cells (HUVECs) stimulated with lipopolysaccharide (LPS). METHODS: The effect of DXM on expression of cell adhesion molecules induced by LPS was evaluated by monocyte bindings in vitro and ex vivo and transmigration assays. The signaling pathways involved in the inflammation inhibitory effect of DXM were analyzed by Western blot and immunofluorescent stain. RESULTS: Pretreatment of HUVECs with DXM inhibited LPS-induced adhesion of THP-1 cells in vitro and ex vivo, and reduced transendothelial migration of these cells. Furthermore, treatment of HUVECs with DXM can significantly decrease LPS-induced expression of ICAM-1 and VCAM-1. DXM abrogated LPS-induced phosphorylation of ERK and Akt. The translocation of early growth response gene-1 (Egr-1), a downstream transcription factor involved in the mitogen-activated kinase (MEK)-ERK signaling pathway, was suppressed by DXM treatment. Furthermore, DXM inhibited LPS-induced IκBα degradation and nuclear translocation of p65. CONCLUSIONS: Dextromethorphan inhibits the adhesive capacity of HUVECs by reducing the LPS-induced ICAM-1 and VCAM-1 expression via the suppression of the ERK, Akt, and NF-κB signaling pathways. Thus, DXM is a potential anti-inflammatory therapeutic that may modulate atherogenesis.

The Dual Antimelanogenic and Antioxidant Activities of the Essential Oil Extracted from the Leaves of Acorus macrospadiceus (Yamamoto) F. N. Wei et Y. K. Li.

The antimelanogenic and antioxidant activities of the essential oil extracted from the leaves of Acorus macrospadiceus (Yamamoto) F. N. Wei et Y. K. Li have never been explored. The essential oil effectively inhibited mushroom tyrosinase activity (EC(50) = 1.57 mg/mL) and B16F10 tyrosinase activity (IC(50) = 1.01 mg/mL), decreased the melanin content (EC(50) = 1.04 mg/mL), and depleted the cellular level of the reactive oxygen species (ROS) (EC(50) = 1.87 mg/mL). The essential oil effectively scavenged 2,2-diphenyl-1-picryl-hydrazyl (DPPH) (EC(50) = 0.121 mg/mL) and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) ABTS(+) radicals (EC(50) = 0.122 mg/mL). It also exhibited an apparent reducing power (EC(50) = 0.021 mg/mL) and metal-ion chelating activity (EC(50) = 0.029 mg/mL). The chemical constituents of the essential oil are ethers (55.73%), ketones (19.57%), monoterpenes (7.82%), alcohols (3.85%), esters (3.77%), sesquiterpenes (3.72%), and aromatic compounds (2.85%). The results confirm that A. macrospadiceus essential oil is a natural antioxidant and inhibitor of melanogenesis.

Inhibition of melanogenesis and antioxidant properties of Magnolia grandiflora L. flower extract.

BACKGROUND: Magnolia grandiflora L. flower is wildly used in Asian as a traditional herbal medication. The purpose of the study was to investigate the antimelanogenic and antioxidant properties of Magnolia grandiflora L. flower extract. In the study, the inhibitory effects of M. grandiflora L. flower extract on mushroom tyrosinase, B16F10 intracellular tyrosinase activity and melanin content were determined spectrophotometrically. Meanwhile, the antioxidative capacity of the flower extract was also investigated. RESULTS: Our results revealed that M. grandiflora L. flower extract inhibit mushroom tyrosinase activity (IC(50) = 11.1%; v/v), the flower extract also effectively suppressed intracellular tyrosinase activity (IC(50) = 13.6%; v/v) and decreased the amount of melanin (IC(50) = 25.6%; v/v) in a dose-dependent manner in B16F10 cells. Protein expression level of tyrosinase and tyrosinase-related protein 1 (TRP-1) were also decreased by the flower extract. Additionally, antioxidant capacities such as ABTS(+) free radical scavenging activity, reducing capacity and total phenolic content of the flower extract were increased in a dose-dependent pattern. CONCLUSIONS: Our results concluded that M. grandiflora L. flower extract decreased the expression of tyrosinase and TRP-1, and then inhibited melanogenesis in B16F10 cells. The flower extract also show antioxidant capacities and depleted cellular reactive oxygen species (ROS). Hence, M. grandiflora L. flower extract could be applied as a type of dermatological whitening agent in skin care products.

Dual bioactivities of essential oil extracted from the leaves of Artemisia argyi as an antimelanogenic versus antioxidant agent and chemical composition analysis by GC/MS.

The study was aimed at investigating the antimelanogenic and antioxidant properties of essential oil when extracted from the leaves of Artemisia argyi, then analyzing the chemical composition of the essential oil. The inhibitory effect of the essential oil on melanogenesis was evaluated by a mushroom tyrosinase activity assay and B16F10 melanoma cell model. The antioxidant capacity of the essential oil was assayed by spectrophotometric analysis, and the volatile chemical composition of the essential oil was analyzed with gas chromatography-mass spectrometry (GC/MS). The results revealed that the essential oil significantly inhibits mushroom tyrosinase activity (IC(50) = 19.16 mg/mL), down-regulates B16F10 intracellular tyrosinase activity and decreases the amount of melanin content in a dose-dependent pattern. Furthermore, the essential oil significantly scavenged 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) ABTS radicals, showed an apparent reduction power as compared with metal-ion chelating activities. The chemicals constituents in the essential oil are ether (23.66%), alcohols (16.72%), sesquiterpenes (15.21%), esters (11.78%), monoterpenes (11.63%), ketones (6.09%), aromatic compounds (5.01%), and account for a 90.10% analysis of its chemical composition. It is predicted that eucalyptol and the other constituents, except for alcohols, in the essential oil may contribute to its antioxidant activities. The results indicated that essential oil extracted from A. argyi leaves decreased melanin production in B16F10 cells and showed potent antioxidant activity. The essential oil can thereby be applied as an inhibitor of melanogenesis and could also act as a natural antioxidant in skin care products.

Antioxidative characteristics of Anisomeles indica extract and inhibitory effect of ovatodiolide on melanogenesis.

The purpose of the study was to investigate the antioxidant characteristics of Anisomeles indica methanol extract and the inhibitory effect of ovatodiolide on melanogenesis. In the study, the antioxidant capacities of A. indica methanol extract such as DPPH assay, ABTS radical scavenging assay, reducing capacity and metal ion chelating capacity as well as total phenolic content of the extract were investigated. In addition, the inhibitory effects of ovatodiolide on mushroom tyrosinase, B16F10 intracellular tyrosinase and melanin content were determined spectrophotometrically. Our results revealed that the antioxidant capacities of A. indica methanol extract increased in a dose-dependent pattern. The purified ovatodiolide inhibited mushroom tyrosinase activity (IC(50) = 0.253 mM), the compound also effectively suppressed intracellular tyrosinase activity (IC(50) = 0.469 mM) and decreased the amount of melanin (IC(50) = 0.435 mM) in a dose-dependent manner in B16F10 cells. Our results concluded that A. indica methanol extract displays antioxidant capacities and ovatodiolide purified from the extract inhibited melanogenesis in B16F10 cells. Hence, A. indica methanol extract and ovatodiolide could be applied as a type of dermatological whitening agent in skin care products.

Inhibition of melanogenesis versus antioxidant properties of essential oil extracted from leaves of Vitex negundo Linn and chemical composition analysis by GC-MS.

This study was aimed at investigating the antimelanogenic and antioxidative properties of the essential oil extracted from leaves of V. negundo Linn and the analysis of the chemical composition of this essential oil. The efficacy of the essential oil was evaluated spectrophotometrically, whereas the volatile chemical compounds in the essential oil were analyzed by gas chromatography-mass spectrometry (GC-MS). The results revealed that the essential oil effectively suppresses murine B16F10 tyrosinase activity and decreases the amount of melanin in a dose-dependent manner. Additionally, the essential oil significantly scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radicals, and showed potent reducing power versus metal-ion chelating properties in a dose-dependent pattern. The chemical constituents in the essential oil are sesquiterpenes (44.41%), monoterpenes (19.25%), esters (14.77%), alcohols (8.53%), aromatic compound (5.90%), ketone (4.96%), ethers (0.4%) that together account for 98.22% of its chemical composition. It is predicted that the aromatic compound in the essential oil may contribute to its antioxidant activities. The results indicated that essential oil extracted from V. negundo Linn leaves decreased melanin production in B16F10 melanoma cells and showed potent antioxidant activities. The essential oil can thereby serve as an inhibitor of melanin synthesis and could also act as a natural antioxidant.

Antioxidative properties and inhibitory effect of Bifidobacterium adolescentis on melanogenesis.

Melanin is a dark pigment produced by melanocytes. Tyrosinase is a key enzyme which catalyzes the rate-limiting step of melanogenesis. However, accumulation of melanin leads to various skin hyperpigmentation disorders. To find a novel skin-whitening agent, the antioxidant capacity of Bifidobacterium adolescentis culture filtrate and inhibitory effect on melanogenesis were investigated. The antioxidant effects of B. adolescentis culture filtrate include 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging capacity, 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) radical cation scavenging activity and reducing power were measured spectrophotometrically. The reducing power is a useful index for the evaluation of potential antioxidants which carry out reduction of ferricyanide to ferrocyanide. Furthermore, the inhibitory effects of the bacterial culture filtrate on mushroom tyrosinase, B16F10 intracellular tyrosinase activity and melanin content were also determined. The results revealed that B. adolescentis culture filtrate (2.5, 5.0 and 7.5 %; v/v) effectively scavenged DPPH and ABTS radicals, and lower concentrations of the bacterial culture filtrates (0.5, 1.0 and 1.5 %; v/v) showed potent reducing power in a dose-dependent pattern. Additionally, the bacterial culture filtrate suppressed murine tyrosinase activity and decreased the amount of melanin in a dose-dependent manner. Our results demonstrated that B. adolescentis culture filtrate decreases the melanogenesis process of melanoma cells by inhibiting tyrosinase activity, which we suggest may be mediated through its antioxidant activity.

Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Attenuate Mast Cell Activation.

The therapeutic potential of extracellular vesicles isolated from stem cells have been reported in several clinical diseases. Preclinical studies have demonstrated the beneficial effects of extracellular vesicles in the treatment of heart, kidney, liver, brain, and skin injuries. To address the putative therapeutic effects and mechanisms of extracellular vesicles derived from human umbilical cord mesenchymal stem cells on allergic activation in mast cells, we isolated extracellular vesicles from human umbilical cord-derived mesenchymal stem cells (UCMSCs) by tangential-flow filtration methods. The characteristics and identification of UCMSC-derived extracellular vesicles were examined via nanoparticle tracking analysis, transmission electron microscopy and protein marker analysis. Cytokines and tryptase in the cultured supernatant of KU812 cells were analyzed using an ELISA kit. Proteins in the MAPK and STAT5 signaling pathways were detected by Western blotting. This study showed that different doses of UCMSC-derived extracellular vesicles abolish IgE-stimulated KU812 cell activation and reduce the level of NF-κB, which subsequently leads to cell degranulation and the release of IL-1ß, TNF-α and IL-6. Additionally, UCMSC-derived extracellular vesicles treatment blunted the IgE-induced signaling proteins p-P38, p-JNK and p-STAT5. Our results revealed a mechanism for anti-inflammation in which extracellular vesicles can affect the activation of mast cells and thus function in allergy regulation.

Inhibitory effect of [6]-gingerol on melanogenesis in B16F10 melanoma cells and a possible mechanism of action.

[6]-Gingerol is an active component of ginger that shows antipyretic and anti-inflammation activities. To find a novel skin-whitening agent, the melanogeneis inhibitory effects and action mechanisms of [6]-gingerol were investigated. In the present study, the effects of [6]-gingerol on mushroom tyrosinase, tyrosinase activity, and melanin content were determined spectrophotometrically, and the expression of tyrosinase and related proteins in B16F10 murine melanoma cells was evaluated by Western blotting. Furthermore, a possible signaling pathway involved in [6]-gingerolmediated depigmentation was investigated by means of specific inhibitors. The results revealed that [6]-gingerol (25-100 µM) effectively suppresses murine tyrosinase activity and decreases the amount of melanin in a dose-dependent manner. Additionally, it also effectively decreased the intracellular reactive oxygen species (ROS) level in a dose-dependent pattern in the same dose range. Our results indicate that [6]-gingerol inhibits melanogenesis of B16F10 melanoma and can function as a good skinwhitening agent.

Effects of salvianolic Acid B on protein expression in human umbilical vein endothelial cells.

Salvianolic acid B (Sal B), a pure water-soluble compound extracted from Radix Salviae miltiorrhizae, has been reported to possess potential cardioprotective efficacy. To identify proteins or pathways by which Sal B might exert its protective activities on the cardiovascular system, two-dimensional gel electrophoresis-based comparative proteomics was performed, and proteins altered in their expression level after Sal B treatment were identified by MALDI-TOF MS/MS. Human umbilical vein endothelial cells (HUVECs) were incubated at Sal B concentrations that can be reached in human plasma by pharmacological intervention. Results indicated that caldesmon, an actin-stabilizing protein, was downregulated in Sal B-exposed HUVECs. Proteins that showed increased expression levels upon Sal B treatment were vimentin, T-complex protein 1, protein disulfide isomerase, tropomyosin alpha, heat shock protein beta-1, UBX domain-containing protein 1, alpha enolase, and peroxiredoxin-2. Additionally, Sal B leads to increased phosphorylation of nucleophosmin in a dose-dependent manner and promotes proliferation of HUVECs. We found that Sal B exhibited a coordinated regulation of enzymes and proteins involved in cytoskeletal reorganization, oxidative stress, and cell growth. Our investigation would provide understanding to the endothelium protection information of Sal B.

Dictamnine delivered by PLGA nanocarriers ameliorated inflammation in an oxazolone-induced dermatitis mouse model.

Dictamnine is an active pharmaceutical ingredient in Dictamnus dasycarpus, a Chinese herbal medicine widely used for the treatment of skin inflammations such as atopic dermatitis (AD). Oxazolone has been demonstrated to induce significant skin inflammation and produce inflammatory cytokine expression identical to that of AD. An in vitro HaCaT inflammation model treated with dictamnine, which efficiently scavenged the reactive oxygen species (ROS) and mitochondrial ROS (mROS), and it reduced interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) expression, NLRP3 inflammasome activation, and NF-κB expression. To explore the anti-inflammatory mechanism of dictamnine and enhance sustained drug release and penetration into epidermal structures in a dermatitis mouse model, we prepared PLGA-nanocarrier-encapsulated dictamnine (Dic-PLGA-NC) in a specifically designed bioreactor, namely an ultrasound composite streams-impinging mixer (U-SiM). Mouse dermatitis model was treated with Dic-PLGA-NC medication, spleens were collected to evaluate body weight ratio, and skin was retrieved for histological examination and two-photon microscopy. The data demonstrate that Dic-PLGA-NC efficiently penetrated the dermal layer, making it superior to naked dictamnine; moreover, it ameliorated the dermatitis symptoms and inflammatory cytokine expression in vivo. Dic-PLGA-NC produced using the U-SiM bioreactor could be used in new manufacturing processes for drugs to treat AD.

Theophylline enhances melanogenesis in B16F10 murine melanoma cells through the activation of the MEK 1/2, and Wnt/ß-catenin signaling pathways.

Theophylline is a kind of methyl xanthine, which has been suggested to inhibit the activity of phosphodiesterase and increase the intracellular level of cyclic adenine monophosphate (cAMP). Theophylline has also been reported to increase the length and complexity of the dendritic process in melanocytes. However, the mode of action of theophylline in melanogenesis has never been reported. In this study, the effects of theophylline on melanogenesis were evaluated spectrophotometrically by the mushroom tyrosinase activity assay and by the determination of the intracellular tyrosinase activity and melanin content. The expression levels of melanogenesis-related proteins were analyzed by Western blot. The results indicated that theophylline (100-500 µM) effectively enhanced melanogenesis in the B16F10 murine melanoma cells. Moreover, theophylline increased the protein expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein 1 (TRP-1), and the level of phosphorylated extracellular regulated protein kinase (p-ERK) and phosphorylated glycogen synthase kinase-3ß (p-GSK3ß) were also increased. In summary, the results revealed that theophylline promoted melanogenesis in B16F10 cells by upregulating the mitogen-activated protein kinase kinase 1 (MEK 1/2) and Wnt/ß-catenin signaling pathways.

Lactic Acid Bacteria and Lactic Acid for Skin Health and Melanogenesis Inhibition.

Lactic acid bacteria are beneficial to human health. Lactic acid bacteria have wide applications in food, cosmetic and medicine industries due to being Generally Recognized As Safe (GRAS) and a multitude of therapeutic and functional properties. Previous studies have reported the beneficial effects of lactic acid bacteria, their extracts or ferments on skin health, including improvements in skin conditions and the prevention of skin diseases. Lipoteichoic acid isolated from Lactobacillus plantarum was reported to inhibit melanogenesis in B16F10 melanoma cells. In particular, lipoteichoic acid also exerted anti-photoaging effects on human skin cells by regulating the expression of matrix metalloproteinase- 1. The oral administration of Lactobacillus delbrueckii and other lactic acid bacteria has been reported to inhibit the development of atopic diseases. Additionally, the clinical and histologic evidence indicates that the topical application of lactic acid is effective for depigmentation and improving the surface roughness and mild wrinkling of the skin caused by environmental photo-damage. This review discusses recent findings on the effects of lactic acid bacteria on skin health and their specific applications in skin-whitening cosmetics.