RESUMEN
Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the accumulation of amyloid-beta plaques and hyperphosphorylated tau proteins, leading to cognitive decline and neuronal death. However, despite extensive research, there are still no effective treatments for this condition. In this study, a series of chloride-substituted Ramalin derivatives is synthesized to optimize their antioxidant, anti-inflammatory, and their potential to target key pathological features of Alzheimer's disease. The effect of the chloride position on these properties is investigated, specifically examining the potential of these derivatives to inhibit tau aggregation and beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) activity. Our findings demonstrate that several derivatives, particularly RA-3Cl, RA-4Cl, RA-26Cl, RA-34Cl, and RA-35Cl, significantly inhibit tau aggregation with inhibition rates of approximately 50%. For BACE-1 inhibition, Ramalin and RA-4Cl also significantly decrease BACE-1 expression in N2a cells by 40% and 38%, respectively, while RA-23Cl and RA-24Cl showed inhibition rates of 30% and 35% in SH-SY5Y cells. These results suggest that chloride-substituted Ramalin derivatives possess promising multifunctional properties for AD treatment, warranting further investigation and optimization for clinical applications.
Asunto(s)
Enfermedad de Alzheimer , Secretasas de la Proteína Precursora del Amiloide , Ácido Aspártico Endopeptidasas , Proteínas tau , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Humanos , Proteínas tau/metabolismo , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Ácido Aspártico Endopeptidasas/antagonistas & inhibidores , Ácido Aspártico Endopeptidasas/metabolismo , Cloruros/química , Antioxidantes/farmacología , Antioxidantes/síntesis química , Antioxidantes/química , Agregado de Proteínas/efectos de los fármacos , Línea Celular Tumoral , Antiinflamatorios/farmacología , Antiinflamatorios/síntesis química , Antiinflamatorios/químicaRESUMEN
The pathogenesis of Alzheimer's disease (AD) is still unclear, and presently there is no cure for the disease that can be used for its treatment or to stop its progression. Here, we investigated the therapeutic potential of ramalin (isolated from the Antarctic lichen, Ramalina terebrata), which exhibits various physiological activities, in AD. Specifically, derivatives were synthesized based on the structure of ramalin, which has a strong antioxidant effect, BACE-1 inhibition activity, and anti-inflammatory effects. Therefore, ramalin and its derivatives exhibit activity against multiple targets associated with AD and can serve as potential therapeutic agents for the disease.
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Enfermedad de Alzheimer/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Glutamatos/uso terapéutico , Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Antioxidantes/síntesis química , Antioxidantes/química , Ácido Aspártico Endopeptidasas/antagonistas & inhibidores , Ácido Aspártico Endopeptidasas/metabolismo , Compuestos de Bifenilo/antagonistas & inhibidores , Glutamatos/síntesis química , Glutamatos/química , Humanos , Estructura Molecular , Picratos/antagonistas & inhibidoresRESUMEN
The aim of the present study was to determine the anti-inflammatory effect of an extracts isolated from the lichen. Amandinea sp. was collected from the Antarctic and extracted with methanol. The basic screening of the anti-inflammatory property of the extracts was done using the NO assay. The extracts showed very little cytotoxicity, and reduced NO production in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. Furthermore, the extracts inhibited LPS-induced release of pro-inflammatory cytokines such as interleukin-6 (IL-6), and tumor necrosis factor-α(TNF-α), and inflammatory mediators inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The extracts also reduced the cytosolic p-IκB-α level and the level of the nuclear factor p65. We examined the anti-inflammatory effects of the extracts using zebrafish in vivo. The extracts reduced the amount of reactive oxygen species (ROS) in LPS-induced zebrafish larvae and inhibited the mRNA expression of inflammatory cytokines and mediators in a tail-cutting induced model. These results are similar to those obtained in vitro with RAW 264.7 cells. Collectively, the data suggest that the extracts may contain one of more compounds with anti-inflammatory effects. Further studies are required to identify the candidate compound/s and to understand the mechanism of action of the extract.
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Antiinflamatorios/farmacología , Ascomicetos/química , Enfermedades de los Peces/tratamiento farmacológico , Inflamación/veterinaria , Líquenes/química , Pez Cebra/inmunología , Animales , Inflamación/tratamiento farmacológico , Lipopolisacáridos/farmacología , Ratones , Células RAW 264.7RESUMEN
Inflammation triggered by the innate immune system is a strategy to protect organisms from the risk of environmental infection. However, it has recently become clear that inflammation can cause a variety of human diseases, including cancer. In this study, we investigated the effects of an ethanol extract of the Antarctic freshwater microalgae, Chloromonas reticulata (ETCH), on inflammation and carcinogenesis in RAW 264.7 macrophages and HCT116 human colon cancer cells, respectively. ETCH exhibited significant anti-inflammatory activity through the dose-dependent modulation of major inflammatory markers such as COX-2, IL-6, iNOS, TNF-α, and NO production. For example, ETCH reduced LPS-induced upregulation of COX-2, IL-6, iNOS, and TNF- alpha mRNA levels, leading to a significant decrease in the levels of LPS-stimulated NO and IL-6 as well as TNF-alpha products. In contract, ETCH exhibited dose-dependent cytotoxic activity against HCT116 cells, yielding a profound reduction in the proliferation of the cancer cells. Furthermore, ETCH induced G2 phase cell cycle arrest by transcriptionally regulating of genes involved in G2 / M transition including p21 (CDKN1A), cyclin B1 (CCNB1), and CDK1; CDKN1A mRNA levels were upregulated in response to ETCH, whereas CCNB1 and CDK1 were downregulated. This study reports for the first time anti-inflammatory and anti-cancer effects of, C. reticulata and provides new insights into the molecular mechanisms of the linkage between inflammation and cancer.
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Productos Biológicos/uso terapéutico , Inflamación/terapia , Microalgas , Neoplasias/prevención & control , Animales , Productos Biológicos/farmacología , Ciclo Celular/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Lipopolisacáridos , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Células RAW 264.7RESUMEN
Optical pulses from picosecond lasers can be delivered to the skin using microlens array (MLA) optics or a diffractive beam splitter to generate multiple, focused, high-intensity, micro-injury zones in the epidermis and dermis. The aim of our study was to histopathologically and immunohistochemically evaluate the patterns of 532- and 1064-nm MLA-type, picosecond laser-induced tissue reactions in human skin immediately after treatment. Picosecond neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment using an MLA-type beam at the wavelengths of 532 nm and 1064 nm was delivered ex vivo to human skin. Irradiated skin specimens were then microscopically analyzed after hematoxylin and eosin staining and CD31 and Melan-A immunostaining. A single pulse of 532-nm MLA-type, picosecond laser treatment elicited cystic cavitation lesions at sizes of 83.4 ± 16.5 µm × 70.2 ± 17.3 µm (31-mm distance step) and 91.0 ± 44.7 µm × 81.2 ± 36.3 µm (48-mm distance step) in the epidermis and papillary dermis. Meanwhile, a single pulse of 1064-nm laser treatment generated cystic cavitation lesions at sizes of 107.0 ± 18.1 µm × 83.3 ± 37.4 µm (single-pulse mode) and 100.8 ± 40.4 µm × 83.1 ± 29.4 µm (dual-pulse mode) throughout the lower epidermis and upper papillary dermis. Lining epithelial cells in cystic cavitation lesions in the epidermis showed Melan-A-positive immunoreactivity, while cystic cavitation lesions in the dermis exhibited CD31-positive or CD31-negative/Melan-A-negative immunoreactivity. The present data can be used to predict 532- and 1064-nm MLA-type, picosecond-domain laser-induced tissue reactions in human skin.
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Láseres de Estado Sólido , Piel/efectos de la radiación , Femenino , Humanos , Antígeno MART-1/metabolismo , Persona de Mediana Edad , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Factores de TiempoRESUMEN
Inflammation mediated by the innate immune system is an organism's protective mechanism against infectious environmental risk factors. It is also a driver of the pathogeneses of various human diseases, including cancer development and progression. Microalgae are increasingly being focused on as sources of bioactive molecules with therapeutic potential against various diseases. Furthermore, the antioxidant, anti-inflammatory, and anticancer potentials of microalgae and their secondary metabolites have been widely reported. However, the underlying mechanisms remain to be elucidated. Therefore, in this study, we investigated the molecular mechanisms underlying the anti-inflammatory and anticancer activities of the ethanol extract of the Antarctic freshwater microalga Micractinium sp. (ETMI) by several in vitro assays using RAW 264.7 macrophages and HCT116 human colon cancer cells. ETMI exerted its anti-inflammatory activity by modulating the main inflammatory indicators such as cyclooxygenase (COX)-2, interleukin (IL)-6, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and nitric oxide (NO) in a dose-dependent manner. In addition, ETMI exerted cytotoxic activity against HCT116 cells in a dose-dependent manner, leading to significantly reduced cancer cell proliferation. Further, it induced cell cycle arrest in the G1 phase through the regulation of hallmark genes of the G1/S phase transition, including CDKN1A, and cyclin-dependent kinase 4 and 6 (CDK4 and CDK6, respectively). At the transcriptional level, the expression of CDKN1A gradually increased in response to ETMI treatment while that of CDK4 and CDK6 decreased. Taken together, our findings suggest that the anti-inflammatory and anticancer activities of the Antarctic freshwater microalga, Micractinium sp., and ETMI may provide a new clue for understanding the molecular link between inflammation and cancer and that ETMI may be a potential anticancer agent for targeted therapy of colorectal cancer.
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Antineoplásicos/farmacología , Inflamación/tratamiento farmacológico , Microalgas/química , Extractos Vegetales/farmacología , Regiones Antárticas , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Ciclooxigenasa 2 , Etanol , Agua Dulce , Humanos , Lipopolisacáridos , Macrófagos/efectos de los fármacos , Óxido Nítrico , Óxido Nítrico Sintasa de Tipo II , Factor de Necrosis Tumoral alfaRESUMEN
Lobaric acid and lobarstin, secondary metabolites derived from the antarctic lichen Stereocaulon alpnum, exert various biological activities, including antitumor, anti-proliferation, anti-inflammation, and antioxidant activities. However, the underlying mechanisms of these effects have not yet been elucidated in human cervix adenocarcinoma and human colon carcinoma. In the present study, we evaluated the anticancer effects of lobaric acid and lobarstin on human cervix adenocarcinoma HeLa cells and colon carcinoma HCT116 cells. We show that the proliferation of Hela and HCT116 cells treated with lobaric acid and lobarstin significantly decreased in a dose- and time-dependent manner. Using flow cytometry analysis, we observed that the treatment with these compounds resulted in significant apoptosis in both cell lines, following cell cycle perturbation and arrest in G2/M phase. Furthermore, using immunoblot analysis, we investigated the expression of cell cycle and apoptosis-related marker genes and found a significant downregulation of the apoptosis regulator B-cell lymphoma 2 (Bcl-2) and upregulation of the cleaved form of the poly (ADP-ribose) polymerase (PARP), a DNA repair and apoptosis regulator. These results suggest that lobaric acid and lobarstin could significantly inhibit cell proliferation through cell cycle arrest and induction of apoptosis via the mitochondrial apoptotic pathway in cervix adenocarcinoma and colon carcinoma cells. Taken together, our data suggests that lobaric acid and lobarstin might be novel agents for clinical treatment of cervix adenocarcinoma and colon carcinoma.
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Antineoplásicos/farmacología , Benzofuranos/farmacología , Neoplasias del Colon/metabolismo , Hidroxibenzoatos/farmacología , Lactonas/farmacología , Líquenes/química , Salicilatos/farmacología , Neoplasias del Cuello Uterino/metabolismo , Antineoplásicos/aislamiento & purificación , Benzofuranos/química , Benzofuranos/aislamiento & purificación , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Depsidos/química , Depsidos/aislamiento & purificación , Depsidos/farmacología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HCT116 , Células HeLa , Humanos , Hidroxibenzoatos/química , Hidroxibenzoatos/aislamiento & purificación , Lactonas/química , Lactonas/aislamiento & purificación , Estructura Molecular , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Salicilatos/química , Salicilatos/aislamiento & purificación , Neoplasias del Cuello Uterino/tratamiento farmacológicoRESUMEN
BACKGROUND: Cancer is a leading cause of human death around the world and occurs through the highly complex coordination of multiple cellular pathways. Recent studies have revealed that microalgal extracts exhibit considerable pharmaceutical activities, including those against various cancer cells. Thus, microalgae are promising candidates as novel cancer therapeutic drugs. In this study, we evaluated the biological functions of the ethanolic extract of the Antarctic freshwater microalga, Bo tryidiopsidaceae sp., such as its antioxidant, anti-proliferative, apoptotic and anti-invasive properties. METHODS: To estimate antioxidant capacity of ethanol extract of Bo tryidiopsidaceae sp. (ETBO), free radical 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays were used. The anti-proliferative activity of ETBO was assessed in several cancer cell lines (A375, Hs578T and HeLa) and non-tumorigenic keratinocyte cells (HaCaT), using MTT assay. In addition, Annexin V binding was performed to detect ETBO-induced apoptotic cells, and the expression levels of apoptosis-regulating proteins, caspase-3, p53, and Bcl-2, were determined by western blot. Boyden chamber assays were used to determine anti-migratory and anti-invasive properties of ETBO. RESULTS: ETBO exhibited antioxidant activity and concentration-dependent anticancer activities, such as anti-proliferation and pro-apoptotic activities against cancer cells. Furthermore, the expression of the apoptosis-inducing proteins, p53 and caspase-3, significantly increased in response to ETBO, whereas the expression of the anti-apoptotic protein, Bcl-2, decreased. These data imply that ETBO induces apoptosis by caspase activation through the modulation of pro-apoptotic and anti-apoptotic gene, p53 and Bcl-2, respectively. In addition, ETBO significantly inhibited migration and invasion of cervical cancer cells in a concentration-dependent manner. CONCLUSION: In this study, ETBO exhibited considerable anticancer activities, such as inhibition of proliferation, invasion, and migration, as well as induction of apoptosis. These data suggest that ETBO is a promising therapeutic agent in cancer therapy and drug discovery.
Asunto(s)
Antineoplásicos/farmacología , Microalgas/química , Extractos Vegetales/farmacología , Estramenopilos/química , Regiones Antárticas , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Agua Dulce , Células HeLa , Humanos , Extractos Vegetales/químicaRESUMEN
Colorectal cancer is a leading cause of death worldwide and occurs through the highly complex coordination of multiple cellular pathways, resulting in carcinogenesis. Recent studies have increasingly revealed that constituents of lichen extracts exhibit potent pharmaceutical activities, including anticancer activity against various cancer cells, making them promising candidates for new anticancer therapeutic drugs. The main objective of this study was to evaluate the anticancer capacities of ramalin, a secondary metabolite from the Antarctic lichen Ramalina terebrata, in the human colorectal cancer cell line HCT116. In this study, ramalin displayed concentration-dependent anticancer activity against HCT116 cells, significantly suppressing proliferation and inducing apoptosis. Furthermore, ramalin induced cell cycle arrest in the gap 2/mitosis (G2/M) phase through the modulation of hallmark genes involved in the G2/M phase transition, such as tumour protein p53 (TP53), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase 1 (CDK1) and cyclin B1 (CCNB1). At both the transcriptional and translational level, ramalin caused a gradual increase in the expression of TP53 and its downstream gene CDKN1A, while decreasing the expression of CDK1 and CCNB1 in a concentration-dependent manner. In addition, ramalin significantly inhibited the migration and invasion of colorectal cancer cells in a concentration-dependent manner. Taken together, these data suggest that ramalin may be a therapeutic candidate for the targeted therapy of colorectal cancer.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Glutamatos/farmacología , Proteínas de Neoplasias/antagonistas & inhibidores , Regiones Antárticas , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Apoptosis/genética , Puntos de Control del Ciclo Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glutamatos/química , Células HCT116 , Humanos , Líquenes/química , Invasividad Neoplásica/genéticaRESUMEN
The incidence of chronic obstructive pulmonary disease (COPD) has substantially increased in recent decade. Cigarette smoke (CS) is the most important risk factor in the development of COPD. In this study, we investigated the effects of melatonin on the development of COPD using a CS and lipopolysaccharide (LPS)-induced COPD model and cigarette smoke condensate (CSC)-stimulated NCI-H292 cells, a human mucoepidermoid carcinoma cell. On day 4, the mice were treated intranasally with LPS. The mice were exposed to CS for 1 hr per day (8 cigarettes per day) from day 1 to day 7. Melatonin (10 or 20 mg/kg) was injected intraperitoneally 1 hr before CS exposure. Melatonin markedly decreased the neutrophil count in the BALF, with reduction in the proinflammatory mediators and MUC5AC. Melatonin inhibited Erk phosphorylation and Sp1 expression induced by CS and LPS treatment. Additionally, melatonin decreased airway inflammation with a reduction in myeloperoxidase expression in lung tissue. In in vitro experiments, melatonin suppressed the elevated expression of proinflammatory mediators induced by CSC treatment. Melatonin reduced Erk phosphorylation and Sp1 expression in CSC-stimulated H292 cells. In addition, cotreatment of melatonin and Erk inhibitors significantly limited the proinflammatory mediators with greater reductions in Erk phosphorylation and Sp1 expression than that observed in H292 cells treated with Erk inhibitor alone. Taken together, melatonin effectively inhibited the neutrophil airway inflammation induced by CS and LPS treatment, which was closely related to downregulation of Erk phosphorylation. These findings suggest that melatonin has a therapeutic potential for the treatment of COPD.
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Antioxidantes/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Melatonina/farmacología , Moco/metabolismo , Neutrófilos/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Fumar/tratamiento farmacológico , Factor de Transcripción Sp1/metabolismo , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Humanos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Lipopolisacáridos/toxicidad , Masculino , Ratones , Infiltración Neutrófila/efectos de los fármacos , Neutrófilos/patología , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , Ratas , Fumar/efectos adversos , Fumar/metabolismo , Fumar/patologíaRESUMEN
BACKGROUND: Noninvasive monopolar radiofrequency (NMRF) is widely used for dermal and subdermal volumetric heating, yet detailed research on its effects on dermal temperature is scarce. AIMS: This study evaluates the impact of NMRF on dermal temperature and its potential for dermal remodeling using a porcine model. METHODS: Noninvasive monopolar radiofrequency was applied to porcine skin with temperature monitoring via optic fiber technology and forward-looking infrared thermal imaging. Safety was evaluated using nitro blue tetrazolium chloride assessments, and effectiveness was determined through histological examinations before and after treatment. RESULTS: Noninvasive monopolar radiofrequency treatment in a porcine model achieved effective dermal remodeling with no thermal damage, recording peak temperatures of 50°C, 60°C, and 70°C. Histological analysis showed increased collagen density, indicating successful tissue remodeling. CONCLUSION: Noninvasive monopolar radiofrequency is effective in delivering controlled dermal heating and enhancing collagen synthesis, promoting safe and efficient skin tightening and dermal remodeling in a porcine model. It presents a viable option for skin rejuvenation therapies.
RESUMEN
The CO2 atmospheric concentration level hit the record at more than 400 ppm and is predicted to keep increasing as the dependence on fossil fuels is inevitable. The CO2 electrocatalytic conversion becomes an alternative due to its environmental and energy-friendly properties and benign operation condition. Lately, bimetallic materials have drawn significant interest as electrocatalysts due to their distinct properties, which the parents' metal cannot mimic. Herein, the indium-bismuth nanosphere (In16Bi84 NS) was fabricated via the facile liquid-polyol technique. The In16Bi84 NS exhibits exceptional performance for CO2 reduction to formate, with the faradaic efficiency (FE) approaching â¼100% and a corresponding partial current density of 14.1 mA cm-2 at -0.94 V [vs the reversible hydrogen electrode (RHE)]. Furthermore, the FE could be maintained above 90% in a wide potential window (-0.84 to -1.54 V vs the RHE). This superior performance is attributed to the tuned electronic properties induced by the synergistic interaction between In and Bi, enabling the intermediates to be stably adsorbed on the catalyst surface to generate more formate ions.
RESUMEN
Umbilicaria antarctica (UA) is a member of the family Umbilicariaceae. To the best of our knowledge, no studies on its anti-inflammatory effects have been reported yet. In the present study, we examined its ability to suppress inflammatory responses and the molecular mechanisms underlying these abilities using lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells and a zebrafish model of inflammation. We investigated the effects of UA on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated RAW 264.7 cells. To explore the anti-inflammatory mechanisms of UA, we measured the mRNA and protein expression of proinflammatory mediators in LPS-stimulated RAW 264.7 cells using quantitative RT-PCR and western blot analyses, respectively. UA significantly inhibited the production of NO, PGE2, interleukin- (IL-) 6, and tumor necrosis factor- (TNF-) α in the LPS-stimulated RAW 264.7 cells. It also suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor- (NF-) κB activation in LPS-stimulated RAW 264.7 cells and tail pin-cutting-induced zebrafish model. Collectively, these findings indicate that UA significantly inhibits LPS-stimulated inflammatory responses. These effects were considered to be strongly associated with the suppression of NF-κB activation. Overall, our results demonstrate that UA extract exerts strong anti-inflammatory activities in in vitro and in vivo models and suggest that UA may be an effective novel therapeutic agent for the treatment of inflammatory diseases.
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Antiinflamatorios/farmacología , Ascomicetos/química , Mezclas Complejas/farmacología , Líquenes/química , Lipopolisacáridos/toxicidad , Animales , Antiinflamatorios/química , Mezclas Complejas/química , Modelos Animales de Enfermedad , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Metanol/química , Ratones , Células RAW 264.7 , Pez CebraRESUMEN
Optical pulses from picosecond lasers can be delivered to the skin as single, flat-top beams or fractionated beams using a beam splitter or microlens array (MLA). In this study, picosecond neodymium:yttrium aluminum garnet laser treatment using a single flat-top beam and an MLA-type beam at the wavelengths of 532 nm and 1,064 nm were delivered on ex vivo genotype-regulated, pigmented micropig skin. Skin specimens were obtained immediately after treatment and microscopically analyzed. Single flat-top beam treatment at a wavelength of 532 nm and a fluence of 0.05-J/cm2 reduced melanin pigments in epidermal keratinocytes and melanocytes, compared to untreated controls. Additionally, 0.1 J/cm2- and 1.3 J/cm2-fluenced laser treatment at 532 nm elicited noticeable vacuolation of keratinocytes and melanocytes within all epidermal layers. Single flat-top beam picosecond laser treatment at a wavelength of 1,064 nm and a fluence of 0.18 J/cm2 also reduced melanin pigments in keratinocytes and melanocytes. Treatment at 1,064-nm and fluences of 1.4 J/cm2 and 2.8 J/cm2 generated increasing degrees of vacuolated keratinocytes and melanocytes. Meanwhile, 532- and 1,064-nm MLA-type, picosecond laser treatment elicited fractionated zones of laser-induced micro-vacuolization in the epidermis and dermis. Therein, the sizes and degrees of tissue reactions differed according to wavelength, fluence, and distance between the microlens and skin.
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Láseres de Estado Sólido , Pigmentación/efectos de la radiación , Piel/efectos de la radiación , Porcinos/fisiología , Animales , LentesRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
Clausena anisata (Willd.) Hook.f. ex Benth. (CA), which is widely used in traditional medicine, reportedly exerts antitumor, anti-inflammatory and other important therapeutic effects. The aim of the present study was to investigate the potential therapeutic effects of CA in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) and in LPS-stimulated RAW 264.7 cells. Male C57BL/6 mice were administered treatments for 3 days by oral gavage. On day 3, the mice were instilled intranasally with LPS or PBS followed 3 h later by oral CA (30 mg/kg) or vehicle administration. In vitro, CA decreased nitric oxide (NO) production and pro-inflammatory cytokines, such as interleukin (IL)-6 and prostaglandin E2 (PGE2), in LPS-stimulated RAW 264.7 cells. CA also reduced the expression of pro-inflammatory mediators, such as cyclooxygenase-2. In vivo, CA administration significantly reduced inflammatory cell numbers in the bronchoalveolar lavage fluid (BALF) and suppressed pro-inflammatory cytokine levels, including tumor necrosis factor-α (TNF-α), IL-6, and IL-1ß, as well as reactive oxygen species production in the BALF. CA also effectively reduced airway inflammation in mouse lung tissue of an LPS-induced ALI mouse model, in addition to decreasing inhibitor κB (IκB) and nuclear factor-κB (NF-κB) p65 phosphorylation. Taken together, the findings demonstrated that CA inhibited inflammatory responses in a mouse model of LPS-induced ALI and in LPS-stimulated RAW 264.7 cells. Thus, CA is a potential candidate for development as an adjunctive treatment for inflammatory disorders, such as ALI.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Clausena/química , Lipopolisacáridos/inmunología , Pulmón/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/patología , Animales , Antiinflamatorios/química , Citocinas/inmunología , Dinoprostona/inmunología , Interleucina-6/inmunología , Pulmón/inmunología , Pulmón/patología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/química , Especies Reactivas de Oxígeno/inmunología , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Thuja orientalis (TO) may be used as a herbal remedy for the treatment of numerous inflammatory diseases. In the present study, the effects of TO were evaluated on airway inflammation in ovalbumin (OVA)induced allergic asthma and RAW264.7 murine macrophage cells. The effects of TO on the production of proinflammatory mediators, were determined in RAW264.7 cells that had been stimulated with lipopolysaccharide (LPS). Furthermore, an in vivo experiment was performed on mice that were sensitized to OVA and then received an OVA airway challenge. TO was administered by daily oral gavage at a dose of 30 mg/kg, 2123 days after the initial OVA sensitization. TO was shown to reduce nitric oxide production and reduce the relative mRNA expression levels of inducible nitric oxide synthase (iNOS), interleukin (IL)6, cyclooxygenase2, matrix metalloproteinase (MMP)9, and tumor necrosis factorα in RAW264.7 cells stimulated with LPS. In addition, TO markedly decreased the inflammatory cell counts in bronchial alveolar lavage fluid, reduced the levels of IL4, IL5, IL13, eotaxin and immunoglobulin E, and reduced airway hyperresponsivenes, in the OVA sensitized mice. Furthermore, TO attenuated airway inflammation and mucus hypersecretion, induced by the OVA challenge of the lung tissue. TO also reduced the expression of iNOS and MMP9 in lung tissue. In conclusion, TO exerted antiinflammatory effects in an OVAinduced allergic asthma model, and in LPSstimulated RAW264.7 cells. These results suggest that TO may be a useful therapeutic agent for the treatment of inflammatory diseases, including allergic asthma.
Asunto(s)
Antiasmáticos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Asma/tratamiento farmacológico , Pulmón/efectos de los fármacos , Thuja/química , Animales , Antiasmáticos/aislamiento & purificación , Antiinflamatorios no Esteroideos/aislamiento & purificación , Asma/inducido químicamente , Asma/inmunología , Asma/patología , Línea Celular , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/inmunología , Femenino , Regulación de la Expresión Génica , Inmunoglobulina E/genética , Interleucina-6/genética , Interleucina-6/inmunología , Lipopolisacáridos/farmacología , Pulmón/inmunología , Pulmón/patología , Activación de Macrófagos/efectos de los fármacos , Macrófagos , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/inmunología , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/inmunología , Ovalbúmina , Extractos Vegetales/química , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Zingiber mioga (Thunb.) Roscoe (ZM) is a traditional medicine, used to treat inflammatory diseases. The present study aimed to evaluate the inhibitory effects of ZM on the inflammatory response in lipopolysaccharide (LPS)stimulated RAW264.7 murine macrophage cells and in a mouse model of ovalbumin (OVA)induced allergic asthma. Mice received OVA sensitization on day 0 and 14, and were challenged with OVA between days 21 and 23. ZM was administered to the mice at a dose of 30 mg/kg, 1 h prior to OVA challenge. In LPSstimulated RAW264.7 cells, ZM significantly decreased nitric oxide (NO) and tumor necrosis factor (TNF)α production in a concentrationdependent manner, and mRNA expression of inducible NO synthase (iNOS), TNFα and matrix metalloproteinase (MMP)9 was reduced. In addition, treatment with ZM decreased the inflammatory cell count in bronchoalveolar lavage fluid from the mice, and reduced the expression of interleukin (IL)4, IL5, IL13, eotaxin and immunoglobulin E. ZM also reduced airway hyperresponsiveness in OVAchallenged mice, and attenuated the infiltration of inflammatory cells and mucus production in the airways, with a decrease in the expression of iNOS and MMP9 in lung tissue. In conclusion, the results of the present study indicate that ZM effectively inhibits inflammatory responses. Therefore, it may be that ZM has potential as a therapeutic agent for use in inflammatory diseases.
Asunto(s)
Antiasmáticos/farmacología , Asma/tratamiento farmacológico , Pulmón/efectos de los fármacos , Extractos Vegetales/farmacología , Zingiberaceae/química , Animales , Antiasmáticos/química , Asma/inducido químicamente , Asma/genética , Asma/inmunología , Líquido del Lavado Bronquioalveolar/química , Línea Celular , Quimiocina CCL11/antagonistas & inhibidores , Quimiocina CCL11/genética , Quimiocina CCL11/inmunología , Femenino , Expresión Génica , Inmunoglobulina E/genética , Inmunoglobulina E/inmunología , Interleucina-13/antagonistas & inhibidores , Interleucina-13/genética , Interleucina-13/inmunología , Interleucina-4/antagonistas & inhibidores , Interleucina-4/genética , Interleucina-4/inmunología , Interleucina-5/antagonistas & inhibidores , Interleucina-5/genética , Interleucina-5/inmunología , Lipopolisacáridos/farmacología , Pulmón/inmunología , Pulmón/patología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/inmunología , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/inmunología , Ovalbúmina/efectos adversos , Ovalbúmina/antagonistas & inhibidores , Extractos Vegetales/química , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Physalis alkekengi has been traditionally used for the treatment of coughs, middle ear infections, and sore throats in Korea, Europe, and China. It exhibits a variety of pharmacological activities such as anti-inflammatory, anti-oxidant, and anti-cancer effects. The anti-inflammatory effects of the P. alkekengi methanol extract (PA) and its molecular mechanisms have not yet been fully investigated. In the present study, the chromatogram of PA was established by UPLC analysis. The anti-inflammatory effects of PA were also investigated using murine microphage cell lines, RAW 264.7 cells, and a murine model of OVA induced asthma. In LPS-stimulated RAW264.7 cells, PA reduced the MMP-9 expression with decreases in the production of nitric oxide, inteleukin-6, and tumor necrosis factor-α. Furthermore, PA suppressed the phosphorylation of MAPKs, which resulted in the inhibition of AP-1 activation. These effects of PA were consistent with the results of the in vivo experiment. PA-treated mice significantly inhibited inflammatory cell counts and cytokine production in bronchoalveolar lavage fluids and airway-hyperresponsiveness in OVA-induced asthmatic mice. PA treated mice also showed a marked inhibition of inducible nitric oxide synthase and MMP-9 expression. In conclusion, our results suggest that PA may be a valuable therapeutic material in treating various inflammatory diseases, including allergic asthma.