RESUMEN
Ginseng contains many bioactive constituents, including various ginsenosides that are believed to have anti-allergic, anti-oxidant, and immunostimulatory activities; however, its effects on atopic dermatitis (AD) remain unclear. In the current study, we hypothesized that cultivated ginseng (CG) would inhibit 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in NC/Nga mice by regulating the T helper (Th)1/Th2 balance. Also, CG inhibits TNF-α/IFN-γ-induced thymus- and activation-regulated chemokine (TARC) expression through nuclear factor-kappa B (NF-κB)-dependent signaling in HaCaT cells. CG ameliorated DNCB-induced dermatitis severity, serum levels of IgE and TARC, and mRNA expression of TARC, TNF-α, IFN-γ, IL-4, IL-5, and IL-13 in mice. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells in the ears. Furthermore, CG suppressed the TNF-α/IFN-γ-induced mRNA expression of TARC in HaCaT cells. CG inhibited TNF-α/IFN-γ-induced NF-κB activation. These results suggest that CG inhibited the development of the AD-like skin symptoms by modulating Th1 and Th2 responses in the skin lesions in mice and TARC expression by suppressing TNF-α/IFN-γ-induced NF-κB activation in keratinocytes, and so may be a useful tool in the therapy of AD-like skin symptoms.
Asunto(s)
Quimiocina CCL17/metabolismo , Dermatitis Atópica/tratamiento farmacológico , Dinitroclorobenceno/efectos adversos , Interferón gamma/farmacología , Panax/química , Factor de Necrosis Tumoral alfa/farmacología , Animales , Línea Celular , Quimiocina CCL17/sangre , Quimiocina CCL17/genética , Dermatitis Atópica/etiología , Dermatitis Atópica/patología , Humanos , Inmunoglobulina E/sangre , Interleucina-13/genética , Interleucina-13/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Interleucina-5/genética , Interleucina-5/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Queratinocitos/patología , Masculino , Ratones , FN-kappa B/genética , FN-kappa B/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal , Piel/efectos de los fármacos , Piel/patología , Balance Th1 - Th2/efectos de los fármacosRESUMEN
Pleurotus eryngii is a nutritional and medicinal food rich in polysaccharides that enhance the host immune system as a response to various diseases. The present study investigated the effects of P. eryngii extracts (PEE) on the progress of atopic dermatitis (AD)-like skin lesions in NC/Nga mice induced by 2,4-dinitrochlorobenzene (DNCB). We evaluated skin dermatitis severity, ear thickness, histopathological examination, and cytokines level in DNCB-applied mice treated with PEE. Continuous treatment of PEE inhibited the development of the AD-like skin lesions. PEE suppressed DNCB-induced dermatitis severity, serum level of IgE and thymus and activation-regulated chemokine (TARC), and mRNA expression of TNF-α, INF-γ, IL-4, IL-5, and IL-13 in mice. In addition, PEE reduced thickness of the dermis and dermal infiltration of inflammatory cells and mast cells in histopathological examination. These results indicate that PEE inhibits allergic contact dermatitis through the modulating of T helper (Th)1 and Th2 responses and diminishing the inflammatory cells and mast cells infiltration in the skin lesions in NC/Nga mice.
Asunto(s)
Dermatitis Atópica/tratamiento farmacológico , Dinitroclorobenceno/efectos adversos , Pleurotus , Balance Th1 - Th2/efectos de los fármacos , Animales , Quimiocina CCL17/sangre , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/patología , Inmunoglobulina E/sangre , Interferón gamma/genética , Interferón gamma/metabolismo , Interleucina-13/genética , Interleucina-13/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Interleucina-5/genética , Interleucina-5/metabolismo , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Ratones , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Cultivated ginseng (CG) (Panax ginseng C.A. Meyer), an herb used in Korean herbal medicine, has been widely used in China and Japan to treat fatigue and to enhance resistance to many diseases. It contains many bioactive constituents, including various ginsenosides that are believed to have antioxidant, immunostimulatory, and antiaging activities. Previous studies have revealed that treatment with Panax ginseng is significantly associated with reduced photoaging, but the underlying mode of action has not been elucidated. In this study, we hypothesized that CG inhibits ultraviolet B (UVB)-induced collagenase activation through mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB)/activator protein-1 (AP-1)-dependent signaling in human skin fibroblasts. HS68 cells were treated with CG, followed by irradiation with UVB. Those effects were assessed by semiquantitative polymerase chain reaction, Western blotting, and enzymic activity assays. We found that CG increased cell viability and inhibited the production of reactive oxygen species in HS68 cells exposed to UVB irradiation. Pretreatment of HS68 cells with CG inhibited UVB-induced production of matrix metalloproteinase (MMP) 1 and MMP-13. Western blot analysis further revealed that CG markedly suppressed the enhancement of collagen degradation in UVB-exposed HS68 cells. Cultivated ginseng also suppressed UVB-induced activation of NF-κB, c-Jun, and c-Fos and the phosphorylation of MAPKs, which are upstream modulators of NF-κB and AP-1. These results indicate that CG inhibits UVB-induced collagenolytic MMP production by interfering with MAPK/AP-1 and NF-κB signaling and thus may be useful in the prevention and treatment of skin photoaging.
Asunto(s)
Fibroblastos/efectos de los fármacos , Inhibidores de la Metaloproteinasa de la Matriz , Panax/química , Extractos Vegetales/farmacología , Transducción de Señal , Piel/efectos de los fármacos , Rayos Ultravioleta , Western Blotting , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , China , Colagenasas/metabolismo , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Humanos , Japón , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/metabolismo , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Fosforilación , Especies Reactivas de Oxígeno/metabolismo , Piel/citología , Piel/metabolismo , Piel/efectos de la radiación , Envejecimiento de la Piel/efectos de los fármacos , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismoRESUMEN
Saponins from the roots of Platycodon grandiflorum (CKS) have been shown to exhibit many pharmacological activities, including anti-cancer and anti-inflammatory activities and antioxidant effects. However, anti-skin photoaging effects of CKS have not yet been reported. In this study, we investigated the protective effects of CKS against UVA damage on immortalized human keratinocytes (HaCaT). We then explored the inhibitory effects of CKS on UVA-induced MMP-1 and investigated the molecular mechanism underlying those effects. CKS increased the cell viability and inhibited reactive oxygen species (ROS) production in HaCaT cells exposed to UVA irradiation. Pre-treatment of HaCaT cells with CKS inhibited UVA-induced production of MMP-1 and MMP-9. In addition, CKS decreased UVA-induced expression of the inflammatory cytokines IL-1ß and IL-6. Western blot analysis further revealed that CKS markedly suppressed the enhancement of collagen degradation in UVA-exposed HaCaT cells. CKS also suppressed UVA-induced activation of NF-κB or c-Jun and c-Fos, and the phosphorylation of MAPKs, which are upstream modulators of NF-κB and AP-1.
Asunto(s)
Metaloproteinasa 1 de la Matriz/efectos de la radiación , FN-kappa B/genética , Raíces de Plantas/química , Platycodon/química , Saponinas/farmacología , Factor de Transcripción AP-1/genética , Western Blotting , Línea Celular Tumoral , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/efectos de la radiación , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-6/efectos de la radiación , Queratinocitos/citología , Queratinocitos/metabolismo , Queratinocitos/efectos de la radiación , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/efectos de la radiación , FN-kappa B/metabolismo , Fosforilación , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Transducción de Señal , Factor de Transcripción AP-1/metabolismo , Rayos UltravioletaRESUMEN
Anthocyanins have been shown to exert anti-proliferative, anti-inflammatory effects and anti-carcinogenic activity. In the present work, we investigated the protective effects of anthocyanin fraction (AF) from purple sweet potato on tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in HepG2 cell line and in rat liver. The result showed that the oral pretreatment of AF before t-BHP treatment significantly lowered the serum levels of the hepatic enzyme markers (ALT and AST) and reduced oxidative stress of the liver by evaluation of malondialdehyde and glutathione. Histopathological evaluation of the livers also revealed that AF reduced the incidence of liver lesions. The in vitro result showed that AF significantly reduced t-BHP-induced oxidative injury, as determined by cell cytotoxicity, intracellular glutathione content, lipid peroxidation, reactive oxygen species (ROS) levels, and caspases activation. Also, AF up-regulated antioxidant enzymes including heme oxygenase-1 (HO-1), NAD(P)H:quinone reductase, and glutathione S-transferase. Moreover, AF induced Nrf2 nuclear translocation and Akt and ERK1/2 activation, pathways that are involved in inducing Nrf2 nuclear translocation. Taken together, these results suggest that the protective effects of AF against t-BHP-induced hepatotoxicity may, at least in part, be due to its ability to scavenge ROS and to regulate the antioxidant enzyme HO-1 via the Akt and ERK1/2/Nrf2 signaling pathways.
Asunto(s)
Antocianinas/farmacología , Ipomoea batatas/química , Hígado/efectos de los fármacos , terc-Butilhidroperóxido/toxicidad , Alanina Transaminasa/sangre , Animales , Antocianinas/aislamiento & purificación , Aspartato Aminotransferasas/sangre , Línea Celular , Glutatión/metabolismo , Humanos , Hígado/enzimología , Masculino , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Psidium guajava (P. guajava) is an important food crop and medicinal plant with antioxidant, anti-inflammatory, and anti-allergic activities, supporting its traditional uses. However, its precise effects remain unknown. We investigated the effects of P. guajava ethyl acetate extract (PGEA) on IgE-mediated allergic responses in rat mast RBL-2H3 cells. PGEA reduced antigen (DNP-BSA)-induced release of ß-hexosaminidase and histamine in IgE-sensitized RBL-2H3 cells. In addition, it inhibited antigen-induced IL-4 and TNF-α mRNA expression and protein production in IgE-sensitized RBL-2H3 cells. PGEA also suppressed antigen-induced COX-2 mRNA and protein expression in these cells, as well as antigen-induced activation of NFAT and reactive oxygen species. Moreover, it inhibited antigen-induced activation of NF-κB and degradation of IκB-α. To identify the mechanisms underpinning the inhibition of degranulation and cytokine production by PGEA, we examined the activation of intracellular FcεRI signaling molecules. PGEA suppressed antigen-induced phosphorylation of Syk, LAT, Gab2, and PLCγ2 but not Lyn, and inhibited antigen-induced phosphorylation of downstream signaling intermediates including MAP kinases and Akt. Collectively, the anti-allergic effects of PGEA in vitro suggest its possible therapeutic application to inflammatory allergic diseases, in which its inhibition of inflammatory cytokine production and FcεRI-dependent signaling events in mast cells may be hugely beneficial.
Asunto(s)
Acetatos/química , Hipersensibilidad/tratamiento farmacológico , Inmunoglobulina E/inmunología , Extractos Vegetales/uso terapéutico , Receptores de IgE/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Secuencia de Bases , Línea Celular , Cartilla de ADN , Liberación de Histamina/efectos de los fármacos , Hipersensibilidad/inmunología , Fosforilación , Extractos Vegetales/farmacología , Reacción en Cadena de la Polimerasa , Ratas , Especies Reactivas de OxígenoRESUMEN
Anthocyanins of the purple sweet potato exhibit antioxidant and hepatoprotective activities via a multitude of biochemical mechanisms. However, the signaling pathways involved in the actions of anthocyanin-induced antioxidant enzymes against chronic liver injury are not fully understood. We examined whether an anthocyanin fraction (AF) from purple sweet potato may prevent dimethylnitrosamine (DMN)-induced liver injury by inducing antioxidants via nuclear erythroid 2-related factor 2 (Nrf2) pathways and by reducing inflammation. Treatment with AF attenuated the DMN-induced increased serum alanine aminotransferase and aspartate aminotransferase activities. It also prevented the formation of hepatic malondialdehyde and the depletion of glutathione and maintained normal glutathione-S-transferase (GST) activity in the livers of DMN-intoxicated rats. Furthermore, AF increased the expression of Nrf2, NADPH:quinine oxidoreductase-1, heme oxygenase-1, and GSTα, which were reduced by DMN, and decreased the expression of cyclooxygenase-2 and inducible nitric oxide synthase. An increase in the nuclear translocation of nuclear factor kappa B (NF-κB) was observed in the DMN-induced liver injury group, but AF inhibited this translocation. Taken together, these results demonstrate that AF increases the expression of antioxidant enzymes and Nrf2 and at the same time decreases the expression of inflammatory mediators in DMN-induced liver injury. These data imply that AF induces antioxidant defense via the Nrf2 pathway and reduces inflammation via NF-κB inhibition.
Asunto(s)
Antocianinas/farmacología , Ciclooxigenasa 2/metabolismo , Dimetilnitrosamina/antagonistas & inhibidores , Ipomoea batatas/química , Hígado/efectos de los fármacos , Factor 2 Relacionado con NF-E2/fisiología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Animales , Antocianinas/aislamiento & purificación , Western Blotting , Dimetilnitrosamina/toxicidad , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Peroxidación de Lípido , Hígado/enzimología , Hígado/metabolismo , Masculino , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effects of tumor cell migration and invasion by aqueous extract isolated from Prunella vulgaris (PVAE) using in vitro and in vivo assays. PVAE reduced PMA-induced activation of MMP-9 and further inhibited cell invasion and migration. PVAE suppressed PMA-enhanced expression of MMP-9 protein, mRNA and transcription activity levels through suppression of NF-kappaB activation without changing the tissue inhibitor of metalloproteinase level. PVAE inhibited PMA-induced NF-kappaB nuclear translocation, which is upstream of PMA-induced MMP-9 expression and invasion. Furthermore, pretreatment with NF-kappaB activation inhibitor inhibited the PMA-induced MMP-9 expression and activity. PVAE repressed the PMA-induced phosphorylation of ERK1/2, which is upstream signaling molecules in MMP-9 expression. We confirmed that the inhibitory effect of PVAE on lung metastasis and tumor cell growth using B16-F10 melanoma cells or B16-F1 melanoma cells in C57BL/6 mice. The oral administrations of PVAE reduced the lung metastasis and tumor cell growth by B16-F10 or B16-F1 melanoma cells. These results suggested that the anti-metastatic effect of PVAE is mediated through the suppression of MMP-9 expression by the inhibition of NF-kappaB via ERK1/2 signaling pathway as well as MMP-9 activity.