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1.
J Cosmet Dermatol ; 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31328889

RESUMO

BACKGROUND: Botulinum toxin type A (BoNT-A) may directly remodel dermal tissues or induce a loss of normal morphology and cytoplasmic retraction and spread. Intradermal injection was claimed to produce a dermo-lifting effect, including midface lifting by using low concentration with variable dilution. OBJECTIVE: To understand how intradermal BoNT-A achieves tissue lifting, we examined different type of BoNT-A and their effects on dermal fibroblast contraction. METHODS: Normal human dermal fibroblasts were treated with onabotulinumtoxin (ONA), abobotulinumtoxin (ABO), prabotulinumtoxinA (PRABO), incobotulinumtoxinA (INCO), and letibotulinumtoxin A (LETI) in dilutions used in real-world practice. Fifty fibroblasts per dilution were photographed and measured the length to demonstrate their contraction every 2 hours from baseline (0 hours) to 12 hours post-treatment. RESULTS: ONA did not significantly decrease fibroblast lengths, at any timepoint or dilution. At 1:7 dilution ratios, ABO decreased fibroblast lengths after 2 hours and significantly after 10-12 hours. At 1:7, 1:8, 1:9, and 1:10 dilution, PRABO decreased length, and most rapidly at 1:7 and 1:8. At 1:6, 1:8, 1:9, and 1:10 dilution, INCO decreased lengths almost immediately. At 1:6 dilution, INCO decreased lengths almost immediately. At 1:7 dilution, INCO decreased lengths after 2-4 hours, while at 1:8, 1:9, and 1:10 dilution, INCO decreased lenghts nearly imediately. LETI decreased lengths at all dilutions except 1:9, with near-immediate effects at 1:6, 1:7, 1:8, and 1:10. At 1:4 dilution, LETI decreased lengths from 1 hour. CONCLUSIONS: Different commercial preparations of BoNT-A toxins cause different fibroblast contractions in vitro. Product selection and dilution used may affect the clinical outcome of intradermal injection of BoNT-A for face lifting.

2.
Int J Med Sci ; 16(4): 602-606, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31171912

RESUMO

Hyperpigmentation is a type of pigmentary disorder induced by overexpression of melanin content activated severe esthetic problems as melasma, freckle, ephelides, lentigo and other forms on human skin. Several whitening agents have restricted use because of their side effects or stability such as kojic acid, ascorbic acid and hydroquinone can act as cytotoxic substance which associated to dermatitis and skin cancer. To find for the safe substance, this study aimed to find for the ability of several components in Sucrier banana peel (SBP) extracts to inhibit melanogenesis process through p38 signaling pathway in B16F10 mouse melanoma cells. Tyrosinase activity and the cellular melanin content were dose dependent manner decreasing after SBP treatment. Furthermore, SBP decreased the expression of melanogenesis relate protein as microphthalmia-associated transcription factor (MITF) and tyrosinase protein after 24 hours incubation with α-melanocyte stimulating hormones (MSH) stimulating. The findings demonstrated that SBP contained an effective agent for hyperpigmentation inhibitor through p38 signaling pathways without any effect to ERK pathway, and subsequent down-regulate MITF expression and tyrosinase enzyme family production.


Assuntos
Hiperpigmentação/tratamento farmacológico , Melaninas/biossíntese , Melanoma Experimental/tratamento farmacológico , Musa/química , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melaninas/antagonistas & inibidores , Melanoma Experimental/genética , Melanoma Experimental/patologia , Camundongos , Fator de Transcrição Associado à Microftalmia/genética , Monofenol Mono-Oxigenase/genética , Extratos Vegetais/química , Extratos Vegetais/farmacologia , alfa-MSH/farmacologia
3.
Redox Biol ; 24: 101206, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31039479

RESUMO

We tested whether novel CYP11A1-derived vitamin D3- and lumisterol-hydroxyderivatives, including 1,25(OH)2D3, 20(OH)D3, 1,20(OH)2D3, 20,23(OH)2D3, 1,20,23(OH)3D3, lumisterol, 20(OH)L3, 22(OH)L3, 20,22(OH)2L3, and 24(OH)L3, can protect against UVB-induced damage in human epidermal keratinocytes. Cells were treated with above compounds for 24 h, then subjected to UVB irradiation at UVB doses of 25, 50, 75, or 200 mJ/cm2, and then examined for oxidant formation, proliferation, DNA damage, and the expression of genes at the mRNA and protein levels. Oxidant formation and proliferation were determined by the DCFA-DA and MTS assays, respectively. DNA damage was assessed using the comet assay. Expression of antioxidative genes was evaluated by real-time RT-PCR analysis. Nuclear expression of CPD, phospho-p53, and Nrf2 as well as its target proteins including HO-1, CAT, and MnSOD, were assayed by immunofluorescence and western blotting. Treatment of cells with the above compounds at concentrations of 1 or 100 nM showed a dose-dependent reduction in oxidant formation. At 100 nM they inhibited the proliferation of cultured keratinocytes. When keratinocytes were irradiated with 50-200 mJ/cm2 of UVB they also protected against DNA damage, and/or induced DNA repair by enhancing the repair of 6-4PP and attenuating CPD levels and the tail moment of comets. Treatment with test compounds increased expression of Nrf2-target genes involved in the antioxidant response including GR, HO-1, CAT, SOD1, and SOD2, with increased protein expression for HO-1, CAT, and MnSOD. The treatment also stimulated the phosphorylation of p53 at Ser-15, increased its concentration in the nucleus and enhanced Nrf2 translocation into the nucleus. In conclusion, pretreatment of keratinocytes with 1,25(OH)2D3 or CYP11A1-derived vitamin D3- or lumisterol hydroxy-derivatives, protected them against UVB-induced damage via activation of the Nrf2-dependent antioxidant response and p53-phosphorylation, as well as by the induction of the DNA repair system. Thus, the new vitamin D3 and lumisterol hydroxy-derivatives represent promising anti-photodamaging agents.

4.
Life Sci ; 228: 21-29, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31026455

RESUMO

AIMS: Ethanol is known to induce NO release and coronary vasorelaxation. Evidence suggests that K+ channels, especially a Ca2+-activated K+ channel (KCa), may regulate endothelial NO production. We aimed to investigate the ethanol effect on K+ currents in human coronary artery endothelial cells (HCAECs), identify the K+ channel type/subtype and signaling pathway involved, and demonstrate the relevance to ethanol-induced NO release. MAIN METHODS: Ionic currents of cultured HCAECs were studied using whole-cell patch clamp technique. NO production were measured using the fluorescent probe, 2,3-diaminonaphthalene. KEY FINDINGS: We found that ethanol significantly potentiated HCAEC current (maximal increase to 155.68 ±â€¯18.93%, 20 mM ethanol, +80 mV; mean ±â€¯SEM, n = 9). Ethanol-induced current was significantly inhibited by blockers of IKCa or SKCa (intermediate- or small-conductance KCa), but not by blocking other K+ channels. When other known HCAEC channels were inhibited except IKCa, 20 mM ethanol significantly increased IKCa current to 198 ±â€¯25.11% (n = 6), but it could not enhance SKCa current that was similarly isolated. Moreover, ethanol-induced NO release was prevented by blocking IKCa channel, adenosine A2A receptor (A2AR), Gs protein, or protein kinase A (PKA). SIGNIFICANCE: This study was the first to demonstrate that acute ethanol exposure could activate endothelial IKCa channel, via A2AR-Gs-PKA signaling, leading to increased whole-cell current and NO release, which could be an important mechanism underlying ethanol-induced NO release and vasodilation.


Assuntos
Células Endoteliais/efeitos dos fármacos , Etanol/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Óxido Nítrico/metabolismo , Linhagem Celular , Vasos Coronários/citologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Humanos , Transporte de Íons/efeitos dos fármacos , Técnicas de Patch-Clamp
5.
J Cell Sci ; 131(12)2018 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-29880532

RESUMO

Expression of cyclin D1 (CCND1) is required for cancer cell survival and proliferation. This is presumably due to the role of cyclin D1 in inactivation of the RB tumor suppressor. Here, we investigated the pro-survival function of cyclin D1 in a number of cancer cell lines. We found that cyclin D1 depletion facilitated cellular senescence in several cancer cell lines. Senescence triggered by cyclin D1 depletion was more extensive than that caused by the prolonged CDK4 inhibition. Intriguingly, the senescence caused by cyclin D1 depletion was independent of RB status of the cancer cell. We identified a build-up of intracellular reactive oxygen species in the cancer cells that underwent senescence upon depletion of cyclin D1 but not in those cells where CDK4 was inhibited. The higher ROS levels were responsible for the cell senescence, which was instigated by the p38-JNK-FOXO3a-p27 pathway. Therefore, expression of cyclin D1 prevents cancer cells from undergoing senescence, at least partially, by keeping the level of intracellular oxidative stress at a tolerable sub-lethal level. Depletion of cyclin D1 promotes the RB-independent pro-senescence pathway and the cancer cells then succumb to the endogenous oxidative stress levels.This article has an associated First Person interview with the first author of the paper.


Assuntos
Ciclina D1/deficiência , Neoplasias/metabolismo , Neoplasias/patologia , Estresse Oxidativo/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Senescência Celular/fisiologia , Ciclina D1/metabolismo , Humanos , Células MCF-7 , Proteína do Retinoblastoma/metabolismo
6.
J Pineal Res ; 65(2): e12501, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29702749

RESUMO

Melatonin and its derivatives (N1 -acetyl-N2 -formyl-5-methoxykynurenine [AFMK] and N-acetyl serotonin [NAS]) have broad-spectrum protective effects against photocarcinogenesis, including both direct and indirect antioxidative actions, regulation of apoptosis and DNA damage repair; these data were primarily derived from in vitro models. This study evaluates possible beneficial effects of melatonin and its active derivatives against ultraviolet B (UVB)-induced harm to human and porcine skin ex vivo and to cultured HaCaT cells. The topical application of melatonin, AFMK, or NAS protected epidermal cells against UVB-induced 8-OHdG formation and apoptosis with a further increase in p53ser15 expression, especially after application of melatonin or AFMK but not after NAS use. The photoprotective action was observed in pre- and post-UVB treatment in both human and porcine models. Melatonin along with its derivatives upregulated also the expression of antioxidative enzymes after UVB radiation of HaCaT cells. The exogenous application of melatonin or its derivatives represents a potent and promising tool for preventing UVB-induced oxidative stress and DNA damage. This protection results in improved genomic, cellular, and tissue integrity against UVB-induced carcinogenesis, especially when applied prior to UV exposure. In addition, our ex vivo experiments provide fundamental justification for further testing the clinical utility of melatonin and metabolites as protectors again UVB in human subjects. Our ex vivo data constitute the bridge between vitro to vivo translation and thus justifies the pursue for further clinical utility of melatonin in maintaining skin homeostasis.


Assuntos
Dano ao DNA , Desoxiguanosina/análogos & derivados , Melatonina/farmacologia , Estresse Oxidativo , Pele/metabolismo , Raios Ultravioleta/efeitos adversos , Animais , Linhagem Celular , Desoxiguanosina/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Pele/patologia , Suínos
7.
Phytother Res ; 32(8): 1546-1554, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29672960

RESUMO

Thai herbal antipyretic 22 formula (APF22), a polyherbal formula, has been traditionally used to treat dermatologic problems including hyperpigmentation. Exposure of the skin to ultraviolet A (UVA) causes abnormal melanin production induced by photooxidative stress. This study thus aimed to investigate the protective effects of APF22 extracts and phenolic compounds, ferulic acid (FA), and gallic acid (GA; used as positive control and reference compounds), on melanogenesis through modulation of nuclear factor E2-related factor 2 (Nrf2) signaling and antioxidant defenses in mouse melanoma (B16F10) cells exposed to UVA. Our results revealed that the APF22 extracts, FA, and GA reduced melanin synthesis as well as activity and protein levels of tyrosinase in UVA-irradiated B16F10 cells. Moreover, APF22 extracts and both FA and GA were able to activate Nrf2-antioxidant response element signaling and promote antioxidant defenses including glutathione, catalase, glutathione peroxidase, and the glutathione-S-transferase at both mRNA and enzyme activity levels in irradiated cells. In conclusion, APF22 extracts suppressed UVA-mediated melanogenesis in B16F10 cells possibly via redox mechanisms involving activation of Nrf2 signaling and upregulation of antioxidant defenses. Moreover, pharmacological action of the APF22 extracts may be attributed to the phenolic compounds, FA, and GA, probably serving as the APF22's active compounds.


Assuntos
Antipiréticos/farmacologia , Melaninas/biossíntese , Extratos Vegetais/farmacologia , Raios Ultravioleta , Animais , Elementos de Resposta Antioxidante , Antioxidantes/metabolismo , Catalase/metabolismo , Linhagem Celular Tumoral , Ácidos Cumáricos/farmacologia , Ácido Gálico/farmacologia , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Melanoma Experimental , Camundongos , Monofenol Mono-Oxigenase/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Pele/efeitos dos fármacos , Tailândia
8.
Free Radic Biol Med ; 108: 918-928, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28495448

RESUMO

Responses of melanocytes (MC) to ultraviolet (UV) irradiation can be influenced by their neighbouring keratinocytes (KC). We investigated the role of Nrf2 in regulating paracrine effects of KC on UVB-induced MC responses through phosphorylation of MAPKs in association with oxidative stress in primary human MC cocultured with primary human KC using a transwell co-culture system and small-interfering RNA-mediated silencing of Nrf2 (siNrf2). The mechanisms by which Nrf2 modulated paracrine factors including α-melanocyte-stimulating hormone (α-MSH) and paracrine effects of KC on UVB-mediated apoptosis were also assessed. Our findings showed that co-culture of MC with siNrf2-transfected KC enhanced UVB-mediated cyclobutane pyrimidine dimer (CPD) formation, apoptosis and oxidant formation, together with phosphorylation of ERK, JNK and p38 in MC. Treatment of MC with conditioned medium (CM) from Nrf2-depleted KC also increased UVB-mediated MC damage, suggesting that KC modulated UVB-mediated MC responses via paracrine effects. Additionally, depletion of Nrf2 in KC suppressed UVB-induced α-MSH levels as early as 30min post-irradiation, although pretreatment with N-acetylcysteine (NAC) elevated its levels in CM from siNrf2-transfected KC. Furthermore, NAC reversed the effect of CM from Nrf2-depleted KC on UVB-induced apoptosis and inflammatory response in MC. Our study demonstrates for the first time that KC provided a rescue effect on UVB-mediated MC damage, although depletion of Nrf2 in KC reversed its protective effects on MC in a paracrine fashion in association with elevation of ROS levels and activation of MAPK pathways in MC. Nrf2 may indirectly regulate the paracrine effects of KC probably by affecting levels of the paracrine factor α-MSH via a ROS-dependent mechanism.


Assuntos
Queratinócitos/fisiologia , Melanócitos/fisiologia , Fator 2 Relacionado a NF-E2/metabolismo , Apoptose , Células Cultivadas , Técnicas de Cocultura , Dano ao DNA , Humanos , Sistema de Sinalização das MAP Quinases , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo , Comunicação Parácrina , Cultura Primária de Células , Dímeros de Pirimidina/metabolismo , RNA Interferente Pequeno/genética , Transdução de Sinais , Raios Ultravioleta , alfa-MSH/metabolismo
9.
BMC Complement Altern Med ; 17(1): 32, 2017 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-28068976

RESUMO

BACKGROUND: Pain is the main symptom of most musculoskeletal disorders and can be caused by inflammation in association with oxidative stress. Thai herbal Sahatsatara formula (STF), a polyherbal formula, has been traditionally used for relieving muscle pain and limb numbness. This study aimed to investigate biologically active compounds of STF and its pharmacological effects related to antioxidant and anti-inflammatory activities. METHODS: The identification of possibly active compounds of STF was performed by high performance liquid chromatography (HPLC). Moreover, this study also assessed the free radical scavenging activities of STF and its components using DPPH radical scavenging assay and their inhibitory effects on IL-1ß-induced intracellular reactive oxygen species (ROS) formation in primary human dermal fibroblasts (NHDFs) using DCFDA-flow cytometry analysis. Modulation of human gene expression by STF and its active compounds was investigated by microarray analyzed through Gene Ontology (GO) classification and pathway enrichment analysis. RESULTS: HPLC analysis has revealed the presence of gallic acid (GA) and piperine (PP) as the major compounds in STF extracts. Our finding discovered that STF and its active compounds (GA and PP) yielded free radical scavenging activities and abilities to inhibit IL-1ß-induced cellular ROS formation in NHDFs. Furthermore, microarray analysis demonstrated that a total of 84 genes (54 upregulated and 30 downregulated) were significantly affected by IL-1ß involved in inflammatory cytokines, chemokines, transcription factors, cell adhesion molecules and other immunomodulators participating in NF-κB signaling. The significantly upregulated genes in IL-1ß-treated in NHDFs participate in interleukin and cholecystokinin (CCRK) signaling pathways. The GO analysis of the target genes showed that all test compounds including indomethacin, STF and its active compounds, can downregulate the genes involved in NF-кB signaling pathway in IL-1ß-treated NHDFs compared to the cells treated with IL-1ß alone. CONCLUSIONS: STF and its active compounds possessing antioxidant actions can modulate the effects of IL-1ß-mediated alteration of gene expression profiles associated with inflammatory signaling in NHDFs.


Assuntos
Alcaloides/farmacologia , Antioxidantes/farmacologia , Benzodioxóis/farmacologia , Fibroblastos/efeitos dos fármacos , Ácido Gálico/farmacologia , Interleucina-1beta/metabolismo , Piperidinas/farmacologia , Extratos Vegetais/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Anti-Inflamatórios/farmacologia , Fibroblastos/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Plantas Medicinais/química , Pele/citologia , Pele/efeitos dos fármacos , Pele/metabolismo , Tailândia , Transcriptoma/efeitos dos fármacos
10.
J Pharmacol Exp Ther ; 360(3): 388-398, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28011874

RESUMO

UVA irradiation plays a role in premature aging of the skin through triggering oxidative stress-associated stimulation of matrix metalloproteinase-1 (MMP-1) responsible for collagen degradation, a hallmark of photoaged skin. Compounds that can activate nuclear factor E2-related factor 2 (Nrf2), a transcription factor regulating antioxidant gene expression, should therefore serve as effective antiphotoaging agents. We investigated whether genetic silencing of Nrf2 could relieve UVA-mediated MMP-1 upregulation via activation of mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) signaling using human keratinocyte cell line (HaCaT). Antiphotoaging effects of hispidulin (HPD) and sulforaphane (SFN) were assessed on their abilities to activate Nrf2 in controlling MMP-1 and collagen expressions in association with phosphorylation of MAPKs (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38), c-Jun, and c-Fos, using the skin of BALB/c mice subjected to repetitive UVA irradiation. Our findings suggested that depletion of Nrf2 promoted both mRNA expression and activity of MMP-1 in the UVA-irradiated HaCaT cells. Treatment of Nrf2 knocked-down HaCaT cells with MAPK inhibitors significantly suppressed UVA-induced MMP-1 and AP-1 activities. Moreover, pretreatment of the mouse skin with HPD and SFN, which could activate Nrf2, provided protective effects against UVA-mediated MMP-1 induction and collagen depletion in correlation with the decreased levels of phosphorylated MAPKs, c-Jun, and c-Fos in the mouse skin. In conclusion, Nrf2 could influence UVA-mediated MMP-1 upregulation through the MAPK/AP-1 signaling cascades. HPD and SFN may therefore represent promising antiphotoaging candidates.


Assuntos
Colágeno/metabolismo , Flavonas/farmacologia , Isotiocianatos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Envelhecimento da Pele , Raios Ultravioleta/efeitos adversos , Senilidade Prematura/etiologia , Senilidade Prematura/metabolismo , Animais , Antimutagênicos/farmacologia , Linhagem Celular , Ativação Enzimática/efeitos da radiação , Humanos , Queratinócitos , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Metaloproteinase 1 da Matriz/metabolismo , Camundongos , Estresse Oxidativo , Pele/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Fator de Transcrição AP-1/metabolismo , Regulação para Cima/efeitos da radiação
11.
Stem Cells Int ; 2016: 7370642, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27148370

RESUMO

Skin is the largest human organ. Skin continually reconstructs itself to ensure its viability, integrity, and ability to provide protection for the body. Some areas of skin are continuously exposed to a variety of environmental stressors that can inflict direct and indirect damage to skin cell DNA. Skin homeostasis is maintained by mesenchymal stem cells in inner layer dermis and epidermal stem cells (ESCs) in the outer layer epidermis. Reduction of skin stem cell number and function has been linked to impaired skin homeostasis (e.g., skin premature aging and skin cancers). Skin stem cells, with self-renewal capability and multipotency, are frequently affected by environment. Ultraviolet radiation (UVR), a major cause of stem cell DNA damage, can contribute to depletion of stem cells (ESCs and mesenchymal stem cells) and damage of stem cell niche, eventually leading to photoinduced skin aging. In this review, we discuss the role of UV-induced DNA damage and oxidative stress in the skin stem cell aging in order to gain insights into the pathogenesis and develop a way to reduce photoaging of skin cells.

12.
Oxid Med Cell Longev ; 2016: 5934024, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27057281

RESUMO

Oxidative damage has been suggested to play a role in the pathogenesis of basal cell carcinoma (BCC). This study illustrated an involvement of oxidative DNA damage and changes in antioxidant defenses in BCC by conducting a case-control study (24 controls and 24 BCC patients) and assessing urinary 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dGuo), plasma antioxidant defenses including catalase (CAT), glutathione peroxidase (GPx), NQO1, and total superoxide dismutase (SOD) activities, and glutathione (GSH) levels before surgery and 1 month after surgery. 8-oxo-dGuo expressions as well as protein and mRNA expressions of DNA repair enzyme hOGG1 and antioxidant defenses (CAT, GCLC, GPx, Nrf2, and MnSOD) in nonneoplastic epidermis of control and BCC tissues were also determined. This study observed induction in urinary 8-oxo-dGuo, increased 8-oxo-dGuo expression, and reduced hOGG1 protein and mRNA in BCC tissues, decreased activities of CAT, GPx, and NQO1, but elevated SOD activities and GSH levels in BCC patients and reduction of all antioxidant proteins and genes studied in BCC tissues. Furthermore, decreased plasma antioxidant activities in BCC patients were restored at 1 month after operation compared with preoperative levels. Herein, we concluded that BCC patients were associated with oxidative DNA damage and depletion of antioxidant defenses and surgical removal of BCC correlated with improved redox status.


Assuntos
Antioxidantes/metabolismo , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/cirurgia , Dano ao DNA , Estresse Oxidativo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/sangue , Carcinoma Basocelular/urina , Estudos de Casos e Controles , Dano ao DNA/genética , DNA Glicosilases/genética , DNA Glicosilases/metabolismo , Reparo do DNA/genética , Demografia , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pele/patologia
13.
Redox Biol ; 8: 79-90, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26765101

RESUMO

Dietary phenolics may play a protective role in UV-mediated skin pigmentation through their antioxidant and UV-absorbing actions. In this study, we investigated whether genetic silencing of Nrf2, regulating the transcription of antioxidant genes, affected melanogenesis in primary human epidermal melanocytes (HEMn) and B16F10 melanoma cells subjected to UVA (8J/cm(2)) exposure. Then, we explored the antimelanogenic actions of phenolics; caffeic acid (CA) and ferulic acid (FA) providing partial UVA protection; quercetin (QU) and rutin (RU) providing strong UVA protection and; avobenzone (AV), an efficient UVA filter, in association with modulation of Nrf2-mediated antioxidant defenses in response to UVA insults in B16F10 cells. Upon oxidative insults, Nrf2 silencing promoted melanogenesis in both HEMn and B16F10 cells irradiated with UVA. Stimulation of melanogenesis by UVA correlated with increased ROS and oxidative DNA damage (8-OHdG), GSH depletion as well as a transient downregulation of Nrf2 nuclear translocation and of Nrf2-ARE signaling in B16F10 cells. All test compounds exerted antimelanogenic effects with respect to their abilities to reverse UVA-mediated oxidative damage as well as downregulation of Nrf2 activity and its target antioxidants (GCLC, GST and NQO1) in B16F10 cells. In conclusion, defective Nrf2 may promote melanogenesis under UVA irradiation through oxidative stress mechanisms. Compounds with antioxidant and/or UVA absorption properties could protect against UVA-induced melanogenesis through indirect regulatory effect on Nrf2-ARE pathway.


Assuntos
Antioxidantes/farmacologia , Suplementos Nutricionais , Melaninas/biossíntese , Fator 2 Relacionado a NF-E2/metabolismo , Fenóis/farmacologia , Substâncias Protetoras/farmacologia , Raios Ultravioleta , Animais , Elementos de Resposta Antioxidante , Vias Biossintéticas/efeitos dos fármacos , Vias Biossintéticas/efeitos da radiação , Dano ao DNA/efeitos dos fármacos , Desoxiguanosina/análogos & derivados , Desoxiguanosina/farmacologia , Técnicas de Silenciamento de Genes , Glutationa/metabolismo , Humanos , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Melanócitos/efeitos da radiação , Melanoma/genética , Melanoma/metabolismo , Melanoma Experimental , Camundongos , Monofenol Mono-Oxigenase/metabolismo , Fator 2 Relacionado a NF-E2/genética , Interferência de RNA , Espécies Reativas de Oxigênio/metabolismo , Transcrição Genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-24171043

RESUMO

Ayurved Siriraj HaRak (AVS022) formula has been used for topical remedy of dermatologic disorders. Oxidative stress induced by ultraviolet (UV) A irradiation could be implicated in photoaged skin through triggering matrix metalloproteinase-1 (MMP-1). We, therefore, explored the antioxidant mechanisms by which AVS022 formulation and its individual components protected against UVA-dependent MMP-1 upregulation in keratinocyte HaCaT cells. TLC analysis revealed the presence of multiple phenolics including gallic acid (GA) in the AVS022 extracts. We demonstrated that pretreatment with the whole formula and individual herbal components except T. triandra protected against increased MMP-1 activity in irradiated HaCaT cells. Moreover, all herbal extracts and GA, used as the reference compound, were able to reverse cytotoxicity, oxidant production, glutathione (GSH) loss, and inactivation of catalase and glutathione peroxidase (GPx). F. racemosa was observed to yield the strongest abilities to abolish UVA-mediated induction of MMP-1 and impairment of antioxidant defenses including GSH and catalase. Our observations suggest that upregulation of endogenous antioxidants could be the mechanisms by which AVS022 and its herbal components suppressed UVA-stimulated MMP-1 in HaCaT cells. In addition, pharmacological actions of AVS022 formula may be attributed to the antioxidant potential of its components, in particular F. racemosa, and several phenolics including GA.

15.
BMC Complement Altern Med ; 13: 159, 2013 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-23826868

RESUMO

BACKGROUND: Ayurved Siriraj Brand Wattana formula (AVS073), a Thai herbal formula, has traditionally been used for health promotion and prevention of age-related problems. Ultraviolet A (UVA) is recognized to play a vital role in stimulation of melanin synthesis responsible for abnormal skin pigmentation possibly mediated by photooxidative stress. We thus aimed to study the inhibitory effect of AVS073 extracts on UVA-induced melanogenesis via a redox mechanism involving glutathione (GSH) synthesis and glutathione S-transferase (GST) using human melanoma (G361) cell culture. METHODS: The standardization of AVS073 extracts was carried out by TLC and UHPLC to obtain fingerprinting profiles of the formula, which identified several phenolic compounds including gallic acid (GA) in the formula. Antimelanogenic actions of AVS073 (up to 60 µg/ml) and GA (up to 10 µg/ml) were investigated by measuring tyrosinase activity and mRNA as well as melanin level in G361 cells irradiated with UVA. Moreover, antioxidant actions of the herbal formula and GA were determined by evaluating oxidant formation and modulation of GSH-related antioxidant defenses including GSH content, GST activity and mRNA level of γ-glutamate cysteine ligase catalytic (γ-GCLC) and modifier (γ-GCLM) subunit and GST. RESULTS: AVS073 extracts and GA, used as a reference compound, suppressed UVA-augmented tyrosinase activity and mRNA and melanin formation. In addition, pretreatment with AVS073 and GA was able to inhibit cellular oxidative stress, GSH depletion, GST inactivation and downregulation of γ-GCLC, γ-GCLM and GST mRNA in G361 cells exposed to UVA radiation. CONCLUSIONS: AVS073 formula exerted antimelanogenic effects possibly through improving the redox state by upregulation of GSH and GST. Moreover, pharmacological activity of the polyherbal formula would be attributed to combined action of different phenolic compounds present in the formula.


Assuntos
Antioxidantes/farmacologia , Glutationa/metabolismo , Melaninas/metabolismo , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Antioxidantes/química , Linhagem Celular Tumoral , Química Farmacêutica , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Melaninas/antagonistas & inibidores , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Oxirredução/efeitos dos fármacos , Oxirredução/efeitos da radiação , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Fenóis/química , Extratos Vegetais/química , Substâncias Protetoras/química , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos da radiação , Pigmentação da Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos da radiação , Raios Ultravioleta
16.
J Med Assoc Thai ; 95 Suppl 2: S75-82, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22574533

RESUMO

BACKGROUND: Phyllanthus emblica L. (Indian gooseberry, Ma khaam pom) has been an herbal component of Thai traditional recipes proposed to slow down the aging process. A number of methodologies have been employed to investigate the immunological aspects of the so called "anti-aging effects" of P. emblica in a BALB/c mice model. OBJECTIVE: 1) To investigate the immunological efficacy of the anti-aging effects of P. emblica infusion in a BALB/c mice model. 2) To verify the safety for the consumption of P. emblica infusion in BALB/c mice. MATERIAL AND METHOD: For in vitro studies, splenocytes were isolated from mice and examined in comparison with the human umbilical endothelial cells, fibroblasts and YAC-1 (mouse lymphoma) cells for proliferative activity upon the exposure to P. emblica infusion. For in vivo studies, mice were orally administered with P. emblica infusion at a dose range of 0, 50, 100, 200 mg/kg BW for 14 days. After the treatments, splenocytes isolated from these mice examined for proliferative and NK cell activities. RESULTS: For in vitro studies, the infusion of P. emblica could directly drive the proliferation of mouse splenocytes in a dose-dependent manner. The P. emblica infusion itself was already cytotoxic to YAC-1 in the studied dose, while sparing the human umbilical endothelial cells and fibroblasts. For in vivo studies, splenocytes isolated from these mice exhibited dose-dependent proliferative activities. Only the isolated splenocytes from mice ingesting 100 mg/kg BW exhibited an enhancement in NK cell activity. CONCLUSION: P. emblica infusion could drive proliferative activity of splenocyte in vitro and in vivo, with an enhancement in the NK cell-induced cytotoxic activity. The infusion in the aforementioned dose was safe throughout the study.


Assuntos
Citotoxicidade Imunológica/efeitos dos fármacos , Phyllanthus emblica/imunologia , Extratos Vegetais/farmacologia , Baço/citologia , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Baço/imunologia
17.
Photochem Photobiol ; 88(4): 961-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22360712

RESUMO

Ultraviolet A (UVA) plays a vital role in the pathogenesis of premature skin aging through keratinocyte cytotoxicity and degradation of collagen, a main component of the extracellular matrix providing structural support. Oxidative stress caused by UVA irradiation can mediate induction of matrix metalloprotease-1 (MMP-1), a major enzyme responsible for collagen damage. Protection against UV-mediated disturbance of antioxidant defense system has been proposed as a possible mechanism by which botanical compounds slow down skin aging process. This study therefore aimed to assess inhibitory effects of caffeic acid (CA) and ferulic acid (FA), powerful plant-based phenolic antioxidants, on UVA-induced cytotoxicity and MMP-1 activity and mRNA level through modulation of antioxidant defense mechanism in immortalized human keratinocyte (HaCaT) cells. Pretreatment of the cells with CA or FA prior to UVA irradiation inhibited cytotoxicity, induction of MMP-1 activity and mRNA and oxidant formation. Moreover, CA and FA were able to up-regulate glutathione (GSH) content, γ-glutamate cysteine ligase (γ-GCL) mRNA as well as activities and mRNA expression of catalase and glutathione peroxidase (GPx) in irradiated cells. In conclusion, CA and FA provided protective effects on UVA-mediated MMP-1 induction in HaCaT cells possibly through restoration of antioxidant defense system at the cellular and molecular level.


Assuntos
Ácidos Cafeicos/farmacologia , Ácidos Cumáricos/farmacologia , Queratinócitos/efeitos dos fármacos , Metaloproteinase 1 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Antioxidantes/metabolismo , Catalase/genética , Catalase/metabolismo , Linhagem Celular Transformada , Regulação da Expressão Gênica , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Glutationa/biossíntese , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Metaloproteinase 1 da Matriz/genética , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , RNA Mensageiro/biossíntese , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/patologia , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta
18.
J Photochem Photobiol B ; 108: 16-22, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22244344

RESUMO

Oxidative stress has been suggested to play a role in ultraviolet A (UVA)-mediated melanogenesis. Glutathione (GSH) and GSH-related enzymes including γ-glutamate cysteine ligase (γ-GCL) and glutathione S-transferase (GST) are important antioxidant defenses responsible for maintaining cellular redox balance. Hence, improving GSH redox system to cope with oxidative insults may be essential for attenuation of abnormal melanin production. Gallic acid (GA), a dietary phenolic, has been shown to provide beneficial effects against hyperpigmentation possibly through its antioxidant properties. This study thus aimed to assess the antimelanogenic action of GA with regard to modulation of GSH-GCL system and GST in two melanoma cell lines, lightly pigmented G361 human melanoma and more pigmented B16F10 mouse melanoma cells, irradiated with UVA. G361 cells were shown to have lower basal GSH content and GST activity than B16F10 cells. Moreover, GA provided antimelanogenic effects in correlation with promotion of GSH levels, GST activity as well as γ-GCL and GST mRNA in both G361 and B16F10 cells at 2-h post-irradiation. In summary, GA exhibits protective effects on UVA-mediated melanogenesis possibly through improvement of GSH-related antioxidant defenses. Furthermore, different redox state in G361 and B16F10 cells may affect the responses of melanoma cells to GA.


Assuntos
Antioxidantes/farmacologia , Ácido Gálico/farmacologia , Glutationa/metabolismo , Melaninas/biossíntese , Raios Ultravioleta , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Humanos , Melaninas/metabolismo , Camundongos , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos
19.
Arch Pharm Res ; 34(5): 811-20, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21656367

RESUMO

Ascorbic acid (AA) has been well known as a skin whitening agent, although attempts have been made to evaluate its protective role against ultraviolet (UV)-induced skin hyperpigmentation or increased melanin production. While melanogenesis is a defense mechanism of the skin against UV irradiation, melanin overproduction may also contribute to melanoma initiation. UVA might play a role in melanogenesis through promoting oxidative stress, which occurs as the result of increased formation of oxidants and/or reactive nitrogen species (RNS) including nitric oxide (NO). Therefore, we investigated the antimelanogenic effect of AA (7.5-120 µM) in association with its inhibitory effect on UVA-induced oxidant formation, NO production through endothelial and inducible NO synthases (eNOS and iNOS) activation and impairment of antioxidant defense using G361 human melanoma cells. Our study demonstrated a comparable ability of AA with that of kojic acid, a well-known tyrosinase inhibitor in inhibiting mushroom tyrosinase. Melanin content was reduced by AA, but neither tyrosinase activity nor mRNA levels were reduced by AA at non-cytotoxic concentrations in UVA-irradiated G361 cells. AA was shown to inhibit UVA-mediated catalase (CAT) inactivation, glutathione (GSH) depletion, oxidant formation and NO production through suppression of eNOS and iNOS mRNA. We report herein that AA can protect against UVA-dependent melanogenesis possibly through the improvement of antioxidant defense capacity and inhibition of NO production through down-regulation of eNOS and iNOS mRNA.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Melaninas/metabolismo , Melanócitos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Raios Ultravioleta , Catalase/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Fármacos Dermatológicos/farmacologia , Inibidores Enzimáticos/metabolismo , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos da radiação , Glutationa/metabolismo , Humanos , Melanócitos/metabolismo , Melanócitos/efeitos da radiação , Melanoma/prevenção & controle , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , RNA Mensageiro/metabolismo , Pigmentação da Pele/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos
20.
Cell Biol Toxicol ; 26(2): 103-16, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19288216

RESUMO

Ultraviolet A (UVA) irradiation is suggested to contribute to melanogenesis through promoting cellular oxidative stress and impairing antioxidant defenses. An overproduction of melanin can be associated with melanoma skin cancer and hyperpigmentation. Therefore, developing effective antimelanogenic agents is of importance. Alpinia galanga (AG) and Curcuma aromatica (CA) are traditional medicinal plants widely used for skin problems. Hence, this study investigated the antimelanogenic effects of AG and CA extracts (3.8-30 microg/ml) by assessing tyrosinase activity, tyrosinase mRNA levels, and melanin content in human melanoma cells (G361) exposed to UVA. The roles in protecting against melanogenesis were examined by evaluating their inhibitory effects on UVA-induced cellular oxidative stress and modulation of antioxidant defenses including antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx), and intracellular glutathione (GSH). In addition, possible active compounds accountable for biological activities of the extracts were identified by thin layer chromatography (TLC)-densitometric analysis. Our study demonstrated that UVA (8 J/cm(2)) induced both tyrosinase activity and mRNA levels and UVA (16 J/cm(2))-mediated melanin production were suppressed by the AG or CA extracts at noncytotoxic concentrations. Both extracts were able to protect against UVA-induced cellular oxidant formation and depletion of CAT and GPx activities and GSH content in a dose-dependent manner. Moreover, TLC-densitometric analysis detected the presence of eugenol and curcuminoids in AG and CA, respectively. This is the first report representing promising findings on AG and CA extract-derived antityrosinase properties correlated with their antioxidant potential. Inhibiting cellular oxidative stress and improving antioxidant defenses might be the mechanisms by which the extracts yield the protective effects on UVA-dependent melanogenesis.


Assuntos
Alpinia/química , Curcuma/química , Melanócitos/efeitos dos fármacos , Melanoma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Catalase/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Formazans/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Melaninas/metabolismo , Melaninas/efeitos da radiação , Melanócitos/metabolismo , Melanócitos/efeitos da radiação , Melanoma/metabolismo , Melanoma/radioterapia , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/metabolismo , Estresse Oxidativo/efeitos da radiação , Sais de Tetrazólio/metabolismo , Raios Ultravioleta/efeitos adversos
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