RESUMEN
Echinacea purpurea (L.) Moench (EP), a medicinal plant native to North America, is now cultivated in various regions including Europe. With increasing popularity of Echinacea in Korea recently, a human clinical trial was conducted to evaluate immune-enhancing efficacy and safety of EP 60% ethanolic extract (EPE) in Koreans. Eighty volunteers were recruited for this randomized, double-blind, placebo-controlled clinical trial. They were randomly divided into two groups and given either a daily dose of 200 mg of EPE or a placebo. All participants underwent testing for Natural Killer (NK) cell cytotoxic activity, serum cytokine levels (IL-2, IL-6, IL-10, IL-12, IFN-γ, TNF-α), Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21), and Multidimensional Fatigue Scale (MFS) during this study to assess changes in outcomes. After 8 weeks of EPE consumption, a significant increase in NK cell cytotoxic activity compared to the placebo was observed. Additionally, serum cytokine levels of IL-2, IFN-γ, and TNF-α also significantly increased following EPE consumption. However, no significant changes were observed in WURSS-21 and MFS before and after EPE consumption. Throughout the 8-week study period, no adverse reactions were reported in relation to EPE consumption, and there were no clinically significant changes in diagnostic laboratory tests or vital signs in the EPE group. These results indicate that consumption of EPE could lead to immune improvement without any adverse effects. This clinical trial was the first to demonstrate beneficial effects of EPE consumption on immunity in Korean adults.
Asunto(s)
Citocinas , Echinacea , Células Asesinas Naturales , Extractos Vegetales , Humanos , Método Doble Ciego , Echinacea/química , Masculino , Extractos Vegetales/farmacología , Adulto , Femenino , Células Asesinas Naturales/efectos de los fármacos , Citocinas/sangre , Persona de Mediana Edad , República de Corea , Etanol/química , Adulto JovenRESUMEN
Amomi Fructus is widely used to treat digestive disorders, and Amomum villosum, A. villosum var. xanthioides, and A. longiligulare are permitted medicinally in national pharmacopeias. However, there are a variety of adulterants present in herbal markets owing to their morphological similarities to the genuine Amomum species. Forty-two Amomi Fructus samples from various origins were identified using internal transcribed spacer and chloroplast barcoding analyses, and then their chromatographic profiles were compared using chemometric analysis for chemotaxonomic monitoring. Among the Amomi Fructus samples, A. villosum, A. longiligulare, A. ghaticum, and A. microcarpum were confirmed as single Amomum species, whereas a mixture of either these Amomum species or with another Amomum species was observed in 15 samples. Chemotaxonomic monitoring results demonstrated that two medicinal Amomum samples, A. villosum and A. longiligulare, were not clearly distinguished from each other, but were apparently separated from other non-medicinal Amomum adulterants. A. ghaticum and A. microcarpum samples were also chemically different from other samples and formed their own species groups. Amomum species mixtures showed diverse variations of chemical correlations according to constituent Amomum species. Genetic authentication-based chemotaxonomic monitoring methods are helpful in classifying Amomi Fructus samples by their original species and to distinguish genuine Amomum species from the adulterants.
Asunto(s)
Amomum/química , Amomum/clasificación , Cromatografía Líquida de Alta Presión/métodos , FilogeniaRESUMEN
The lysosomal Ca2+ permeable channel TRPML1 (MCOLN1) plays key roles in lysosomal membrane trafficking, including the fusion of late endosomes to lysosomes and lysosomal exocytosis, both of which are essential for release of exosomes into the extracellular milieu. Multiple lines of evidence indicate that the contents of adipocyte-derived exosomes mediate diverse cellular responses, including adipogenic differentiation. In this study, we aimed to define the potential roles of TRPML1 in lysosomal membrane trafficking during adipogenesis and in exosomal release. In response to adipogenic stimuli, the endogenous TRPML1 expression in OP9 pre-adipocytes was increased in a time-dependent manner, and the acute deletion of TRPML1 reduced lipid synthesis and expression of differentiation-related marker genes. Notably, mature adipocyte-derived exosomes were found to be necessary for adipogenesis and were dependent on TRPML1-mediated lysosomal exocytosis. Taken together, our findings indicate that TRPML1 mediates diverse roles in adipocyte differentiation and exosomal release. Further, we propose that TRPML1 should be considered as a regulator of obesity-related diseases.
Asunto(s)
Adipogénesis , Exocitosis , Exosomas/metabolismo , Lisosomas/fisiología , Canales de Potencial de Receptor Transitorio/fisiología , Animales , Células Cultivadas , Ratones , Canales de Potencial de Receptor Transitorio/antagonistas & inhibidores , Canales de Potencial de Receptor Transitorio/biosíntesisRESUMEN
Novel cage-like indolizine-acenaphthene-pyridinone heterocyclic hybrids were synthesized in good yields through [bmim]Br mediated tandem 1,3-dipolar cycloaddition-annulation sequence. The anti-inflammatory activity of these hybrids was performed using carrageenan-induced hind paw oedema, croton oil-induced ear oedema and cotton pellet-induced granuloma models. Four of these cage-like heterocyclic hybrids viz. 4b, 4d, 4e and 4j showed substantial anti-inflammatory activities against acute and chronic inflammatory models and also showed significant inhibition of PGE2, TNF-α, and nitrite levels in carrageenan-induced hind paw oedema.
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Antiinflamatorios/farmacología , Dinoprostona/antagonistas & inhibidores , Descubrimiento de Drogas , Edema/tratamiento farmacológico , Granuloma/tratamiento farmacológico , Compuestos Heterocíclicos/química , Nitritos/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Antiinflamatorios/química , Carragenina/toxicidad , Edema/inducido químicamente , Edema/patología , Granuloma/inducido químicamente , Granuloma/patología , Ratones , Ratas , Ratas WistarRESUMEN
UVB has been shown to stimulate the generation of reactive oxygen species (ROS), which subsequently results in the activation of various intracellular signalling pathways and transcription factors (AP-1, NF-κB). These transcription factors are regulated by MAPKs, which increase cytokine and MMP expression. We examined the preventive effects of reversine on MMP-1 and MMP-3 expressions in NHEKs and NHDFs exposed to UVB irradiation. Also, we confirmed that reversine decreased pro-inflammatory cytokine expression in NHEKs. The mechanism underlying the MMP inhibitory effects of reversine occurred via the suppression of UVB-induced ROS generation and MAPK/AP-1 activation. Therefore, reversine is an effective therapeutic candidate for preventing skin photoageing.
Asunto(s)
Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/genética , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Morfolinas/farmacología , Purinas/farmacología , Citocinas/genética , Fibroblastos , Expresión Génica/efectos de los fármacos , Humanos , Queratinocitos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación , Factor de Transcripción AP-1/metabolismo , Rayos UltravioletaRESUMEN
The biological function of NADPH oxidase (NOX) is the generation of reactive oxygen species (ROS). ROS, primarily arising from oxidative cell metabolism, play a major role in both chronological ageing and photoageing. ROS in extrinsic and intrinsic skin ageing may be assumed to induce the expression of matrix metalloproteinases. NADPH oxidase is closely linked with phosphatidylinositol 3-OH kinase (PI3K) signalling. Protein kinase C (PKC), a downstream molecule of PI3K, is essential for superoxide generation by NADPH oxidase. However, the effect of PTEN and NOX4 in replicative-aged MMPs expression has not been determined. In this study, we confirmed that inhibition of the PI3K signalling pathway by PTEN gene transfer abolished the NOX-4 and MMP-1 expression. Also, NOX-4 down-expression of replicative-aged skin cells abolished the MMP-1 expression and ROS generation. These results suggest that increase of MMP-1 expression by replicative-induced ROS is related to the change in the PTEN and NOX expression.
Asunto(s)
Senescencia Celular/genética , Fibroblastos/metabolismo , Metaloproteinasa 1 de la Matriz/genética , NADPH Oxidasa 4/genética , Fosfohidrolasa PTEN/genética , Especies Reactivas de Oxígeno/metabolismo , Adenoviridae/genética , Adenoviridae/metabolismo , Células Cultivadas , Dermis/citología , Dermis/metabolismo , Fibroblastos/citología , Regulación de la Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Humanos , Metaloproteinasa 1 de la Matriz/metabolismo , NADPH Oxidasa 4/antagonistas & inhibidores , NADPH Oxidasa 4/metabolismo , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteína Quinasa C/genética , Proteína Quinasa C/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Transducción de Señal , TransfecciónRESUMEN
BACKGROUND: Sophorae Flos (SF) is a composite of flowers and buds of Styphnolobium japonicum (L.) Schott and has been used in traditional Korean and Chinese medicine for the treatment of hemostasis and inflammation. Previous studies reported that SF possesses anti-obesity properties, as well as anti-allergic, anti-proliferative, and anti-inflammatory activities. However, the effect of SF in bone resorption has not been studies. In this study, we examined the potential of SF extract (SFE) to inhibit receptor activator of NF-κB ligand (RANKL) -induced osteoclast differentiation in cultured mouse-derived bone marrow macrophages (BMMs). METHODS: BMMs, that act as osteoclast precursors, were cultured with M-CSF (50 ng/ml) and RANKL (100 ng/ml) for 4 days to generate osteoclasts. Osteoclast differentiation was measured by tartrate-resistant acidic phosphatase (TRAP) staining and the TRAP solution assay. Osteoclast differentiation marker genes were analyzed by the quantitative real-time polymerase chain reaction analysis. RANKLs signaling pathways were confirmed through western blotting. RESULTS: SFE significantly decreased osteoclast differentiation in a dose-dependent manner. SFE inhibited RANKL-induced osteoclastogenesis by suppressing NF-κB activation. By contrast, SFE did not affect phospholipase C gamma 2 or subsequent cAMP response element binding activation. SFE inhibited the RANKL-induced expression of nuclear factor of activated T cells c1 (NFATc1). CONCLUSIONS: SFE attenuated the RANKL-mediated induction of NF-κB through inhibition of IκBα phosphorylation, which contributed to inhibiting of RANKL-induced osteoclast differentiation through downregulation of NFATc1.
Asunto(s)
Células de la Médula Ósea/efectos de los fármacos , Factores de Transcripción NFATC/metabolismo , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Extractos Vegetales/farmacología , Ligando RANK/metabolismo , Sophora/química , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Flores/química , Ratones , Ratones Endogámicos BALB C , FN-kappa B/genética , FN-kappa B/metabolismo , Factores de Transcripción NFATC/genética , Osteoclastos/citología , Osteoclastos/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Acquired resistance to lapatinib is a highly problematic clinical barrier that has to be overcome for a successful cancer treatment. Despite efforts to determine the mechanisms underlying acquired lapatinib resistance (ALR), no definitive genetic factors have been reported to be solely responsible for the acquired resistance in breast cancer. Therefore, we performed a cross-platform meta-analysis of three publically available microarray datasets related to breast cancer with ALR, using the R-based RankProd package. From the meta-analysis, we were able to identify a total of 990 differentially expressed genes (DEGs, 406 upregulated, 584 downregulated) that are potentially associated with ALR. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs showed that "response to organic substance" and "p53 signaling pathway" may be largely involved in ALR process. Of these, many of the top 50 upregulated and downregulated DEGs were found in oncogenesis of various tumors and cancers. For the top 50 DEGs, we constructed the gene coexpression and protein-protein interaction networks from a huge database of well-known molecular interactions. By integrative analysis of two systemic networks, we condensed the total number of DEGs to six common genes (LGALS1, PRSS23, PTRF, FHL2, TOB1, and SOCS2). Furthermore, these genes were confirmed in functional module eigens obtained from the weighted gene correlation network analysis of total DEGs in the microarray datasets ("GSE16179" and "GSE52707"). Our integrative meta-analysis could provide a comprehensive perspective into complex mechanisms underlying ALR in breast cancer and a theoretical support for further chemotherapeutic studies.
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Antineoplásicos , Neoplasias de la Mama/genética , Resistencia a Antineoplásicos/genética , Quinazolinas , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Perfilación de la Expresión Génica , Humanos , Lapatinib , Análisis de Secuencia por Matrices de Oligonucleótidos , Mapas de Interacción de Proteínas , Quinazolinas/uso terapéuticoRESUMEN
Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD(+)) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD(+) in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD(+) levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD(+) levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage.
Asunto(s)
Antineoplásicos/toxicidad , Cisplatino/toxicidad , Intestino Delgado/efectos de los fármacos , NAD/metabolismo , Naftoquinonas/farmacología , Animales , Apoptosis/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Intestino Delgado/metabolismo , Intestino Delgado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Poli(ADP-Ribosa) Polimerasa-1 , Poli(ADP-Ribosa) Polimerasas/metabolismo , Sirtuina 1/metabolismo , Factor de Transcripción ReIA/metabolismoRESUMEN
BACKGROUND: Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus, and has been suggested to possess various biological activities, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral, and cardiotonic activities. The effect of SL on breast cancer metastasis, however, is unknown. Cell migration and invasion are crucial in neoplastic metastasis. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion. METHODS: Cell viability was examined by MTT assay, whereas cell motility was measured by invasion assay. Western blot, Real-time PCR, and Zymography assays were used to investigate the inhibitory effects of ESL on matrix metalloproteinase-9 (MMP-9) expression level in MCF-7 cells. EMSA confirmed the inhibitory effects of ESL on DNA binding of NF- κB in MCF-7 cells. RESULTS: Cells threated with various concentrations of Saussurea lappa (ESL) for 24 h. Concentrations of 2 or 4 µM did not lead to a significant change in cell viability or morphology. Therefore, subsequent experiments utilized the optimal non-toxic concentration (2 or 4 µM) of ESL. In this study, we investigated the inhibitory effect of ethanol extract of ESL on MMP-9 expression and cell invasion in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MCF-7 cells. ESL inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-κB). However, this result obtained that ESL did not block the TPA-induced phosphorylation of the kinases: p38, ERK, and JNK. Therefore, ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. CONCLUSIONS: These results indicate that ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. Thus, ESL has potential for controlling breast cancer invasiveness in vitro.
Asunto(s)
Neoplasias de la Mama/enzimología , Metaloproteinasa 9 de la Matriz/genética , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Saussurea/química , Acetato de Tetradecanoilforbol/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Humanos , Células MCF-7 , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad Neoplásica , Fosforilación/efectos de los fármacos , Activación Transcripcional/efectos de los fármacosRESUMEN
Accumulating evidence indicates that microbial communities in the human body crucially affect health through the production of chemical messengers. However, the relationship between human microbiota and cancer has been underexplored. As a result of a biochemical investigation of the commensal oral microbe, Corynebacterium durum, we identified the non-enzymatic transformation of tryptamine into an anticancer compound, durumamide A (1). The structure of 1 was determined using LC-MS and NMR data analysis as bis(indolyl)glyoxylamide, which was confirmed using one-pot synthesis and X-ray crystallographic analysis, suggesting that 1 is an oxidative dimer of tryptamine. Compound 1 displayed cytotoxic activity against various cancer cell lines with IC50 values ranging from 25 to 35⯵M. A drug affinity responsive target stability assay revealed that survivin is the direct target protein responsible for the anticancer effect of 1, which subsequently induces apoptosis-inducing factor (AIF)-mediated apoptosis. Inspired by the chemical structure and bioactivity of 1, a new derivative, durumamide B (2), was synthesized using another indole-based neurotransmitter, serotonin. The anticancer properties of 2 were similar to those of 1; however, it was less active. These findings reinforce the notion of human microbiota-host interplay by showing that 1 is naturally produced from the human microbial metabolite, tryptamine, which protects the host against cancer.
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Antineoplásicos , Corynebacterium , Neoplasias , Humanos , Survivin , Apoptosis , Factor Inductor de la Apoptosis , Triptaminas/farmacología , Triptaminas/uso terapéutico , Neoplasias/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Estrés Oxidativo , Línea Celular Tumoral , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Proliferación CelularRESUMEN
The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.
Asunto(s)
Chryseobacterium , Fenilacetatos , Vagina , Femenino , Animales , Fenilacetatos/metabolismo , Fenilacetatos/farmacología , Vagina/microbiología , Ratones , Humanos , Chryseobacterium/metabolismo , Candida albicans/metabolismo , Candida albicans/efectos de los fármacos , Simbiosis , Concentración de Iones de Hidrógeno , Gardnerella vaginalis/metabolismo , Gardnerella vaginalis/efectos de los fármacos , Modelos Animales de Enfermedad , Vaginitis/microbiología , Vaginitis/metabolismo , Vaginitis/tratamiento farmacológicoRESUMEN
OBJECTIVE: Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) is one of the active components present in the root and rhizome of Rheum palmatum. It has been shown to contain biological activity (antitumour, antibacterial, diuretic and vasorelaxant effects). However, the mechanisms underlying the anti-arthritic effect of emodin have not been elucidated. Here we investigated whether emodin treatment would modulate the severity of the disease in an experimental arthritis model. METHODS: We evaluated the effects of emodin on CIA mice in vivo. RESULTS: The pathological processes of RA are mediated by a number of cytokines and MMPs. Expression of these proinflammatory mediators is controlled by nuclear factor-κB (NF-κB). This study was performed to explore the effect of emodin on control of the NF-κB activation pathway and to investigate whether emodin has anti-inflammatory effects in CIA mice in vivo. Emodin inhibited the nuclear translocation and DNA binding of NF-κB subunits, which were correlated with its inhibitory effect on cytoplasmic IκBα degradation in CIA mice. These events further suppressed chemokine production and MMP expression. In addition, emodin inhibited the osteoclast differentiation induced by M-CSF and receptor activation of NF-κB ligand in bone marrow macrophages. CONCLUSION: These findings suggest that emodin exerts anti-inflammatory effects in CIA mice through inhibition of the NF-κB pathway and therefore may have therapeutic value for the treatment of RA.
Asunto(s)
Artritis Experimental/tratamiento farmacológico , Emodina/uso terapéutico , Inflamación/tratamiento farmacológico , Articulaciones/efectos de los fármacos , Inhibidores de Proteínas Quinasas/uso terapéutico , Animales , Artritis Experimental/metabolismo , Artritis Experimental/patología , Emodina/farmacología , Articulaciones/metabolismo , Articulaciones/patología , Masculino , Ratones , Ratones Endogámicos DBA , Ratones Endogámicos ICR , FN-kappa B/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Subunidades de Proteína/metabolismo , Transporte de Proteínas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Membrana Sinovial/efectos de los fármacos , Membrana Sinovial/metabolismo , Membrana Sinovial/patologíaRESUMEN
Curcumin (diferuloylmethane) is a polyphenol derived from turmeric (Curcuma longa), which is commonly used as a spice. Recent studies have shown that curcumin has a wide range of pharmacological activities, including anticarcinogenic, antioxidant, anti-inflammatory and antiangiogenic activities. However, the antiphotoageing effects of curcumin have yet to be characterized. In this study, we investigated the inhibitory effects of curcumin on matrix metalloproteinase (MMP)-1 and MMP-3 expression in human dermal fibroblast cells. Western blot analysis revealed that curcumin inhibited ultraviolet (UV) B-induced MMP-1 and MMP-3 expression. Furthermore, curcumin significantly blocked UVB-induced reactive oxygen species generation in fibroblasts. Curcumin treatment significantly blocked the UVB-induced activation of nuclear factor (NF)-κB and activator protein (AP)-1. Additionally, curcumin strongly repressed the UVB-induced phosphorylation of p38 and c-Jun N-terminal kinase. Curcumin prevented UVB-induced MMP expression through mitogen-activated protein kinase/NF-κB inhibition and AP-1 activation. In conclusion, curcumin may be useful for preventing and treating skin photoageing.
Asunto(s)
Curcumina/farmacología , Fibroblastos/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Rayos Ultravioleta/efectos adversos , Dermis/citología , Inhibidores Enzimáticos/farmacología , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Prepucio/citología , Humanos , Sistema de Señalización de MAP Quinasas/efectos de la radiación , Masculino , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Ultraviolet B (UVB) radiation induces photoageing by upregulating the expression of matrix metalloproteinases (MMPs) in human skin cells. Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component in oats. Although anti-inflammatory, anti-atherosclerotic and antioxidant effects have been reported, the antiphotoageing effects of DHAvD are yet to be understood. In this study, we investigated the inhibitory effects of DHAvD on UVB-induced production of reactive oxygen species (ROS) and expression of MMPs, and its molecular mechanism in UVB-irradiated human dermal fibroblasts. Western blot and real-time PCR analyses revealed that DHAvD inhibited UVB-induced MMP-1 and MMP-3 expression. It also significantly blocked UVB-induced ROS generation in fibroblasts. Additionally, DHAvD attenuated UVB-induced phosphorylation of MAPKs, activation of NF-κB and AP-1. DHAvD regulates UVB-irradiated MMP expression by inhibiting ROS-mediated MAPK/NF-κB and AP-1 activation. DHAvD may be a useful candidate for preventing UV light-induced skin photoageing.
Asunto(s)
Fibroblastos/efectos de los fármacos , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Envejecimiento de la Piel/efectos de los fármacos , Piel/efectos de los fármacos , Piel/efectos de la radiación , ortoaminobenzoatos/química , Antiinflamatorios/química , Antioxidantes/química , Núcleo Celular/metabolismo , Fibroblastos/metabolismo , Regulación Enzimológica de la Expresión Génica , Humanos , Fosforilación , Especies Reactivas de Oxígeno , Transducción de Señal , Piel/metabolismo , Rayos UltravioletaRESUMEN
Ginseng has been used as a medicinal herb in Asian countries for hundreds of years. It contains many kinds of ginsenosides as major active ingredients and is known to have neuroprotective, anti-inflammatory, antitumor, and antidiabetic properties. In this study, we have developed cream soup with different concentrations (0%, 3%, 5%, 7%, and 10%) of ginseng powder (GP) and determined the quality characteristics (color, viscosity, salinity, etc.) and antioxidant activity, along with sensory parameters. After the addition of GP, significant differences in salinity, L* and a*color value, DPPH, and ABTS were found among different concentrations of GP. Cream soup supplemented with GP 10% exhibited the highest values for DPPH and ABTS (83.5% and 87%, respectively), while the contents of total phenolic and saponin were 0.651 ± 0.02 (mg Gallic acid Equiv./g, DW) and 0.797 ± 0.05 (mg Diosgenin Equiv./g, DW), respectively. Moreover, there were no significant changes for °Brix value, pH, acidity, and total flavonoids content compared to control. The sensory characteristics indicated bitterness with the increase in the concentration of GP. However, a non-significant difference was observed between the control and supplemented samples for color, viscosity, and overall preference. Therefore, the supplementation of GP to cream soup could exhibit health benefits and increase the demand for ginseng to promote public health as functional food material.
RESUMEN
To apply starch nanoparticles (SNP) as host materials for ß-carotene encapsulation, aqueous SNP dispersions (10, 25, 50, and 100 mg/10 mL) and ß-carotene in acetone (10, 50, 100, 150, and 200 µg/mL) were mixed. The acetone in the mixture was evaporated to prepare SNP and ß-carotene composites, which were homogeneously dispersed in aqueous media with over 90 % solubility. When SNP content was higher than 50 mg, over 80 % of ß-carotene was encapsulated in the composite matrix. X-ray diffraction, nuclear magnetic resonance spectroscopy, and transmission electron microscopic analyses confirmed the micellar-shaped composite particles with diameters <120 nm and an amorphous structure. High SNP content in the composites enhanced ß-carotene stability under extremely hot and acidic conditions as well as against ultraviolet rays and oxidation reactions. The encapsulated ß-carotene was not readily released in simulated gastric fluid, but was gradually released in simulated intestinal fluid via SNP digestion in the composites.
Asunto(s)
Nanopartículas , beta Caroteno , Acetona , Micelas , Nanopartículas/química , Almidón/química , beta Caroteno/químicaRESUMEN
In our previous study, we clearly demonstrated the roles of pro-inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1beta (IL-1beta), and IL-6, and subsequent reactive oxygen species (ROS) generation on the pathogenesis of cisplatin ototoxicity in vitro and in vivo. ROS generation in cisplatin-treated HEI-OC1 auditory cells was also correlated with changing mitochondrial membrane potential. However, the roles of NADPH oxidase in cisplatin-induced ROS generation and ototoxicity have not been fully elucidated. Herein, immunohistochemical studies demonstrated that treatment of cisplatin induced the expression of NADPH oxidase isoforms NOX-1 and NOX-4 in HEI-OC1 auditory cells. Expression of mRNA for NOX-1, NOX-4, NOXO1, NOXA1, p47(phox), and p67(phox) was also increased. Inhibition of NADPH oxidase with diphenyleniodonium chloride or apocynin abolished ROS production and the subsequent apoptotic cell death in cisplatin-treated cells. Furthermore, suppression of NOX1 and NOX4 expression by small interfering RNA transfection markedly abolished the cytotoxicity and ROS generation by cisplatin. Together, our data suggest that ROS generated, in part, through the activation of NADPH oxidase plays an essential role in cisplatin ototoxicity.
Asunto(s)
Cisplatino/toxicidad , Células Ciliadas Auditivas Externas/efectos de los fármacos , Células Ciliadas Auditivas Externas/enzimología , NADPH Oxidasas/fisiología , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Línea Celular Transformada , Cisplatino/administración & dosificación , Cisplatino/antagonistas & inhibidores , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/metabolismo , Inyecciones Intraperitoneales , Masculino , Ratones , Ratones Endogámicos BALB C , Técnicas de Cultivo de Órganos , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/antagonistas & inhibidoresRESUMEN
Butein (3,4,2',4'-tetrahydroxychalcone), a plant polyphenol, is a major component in isolate of Rhus verniciflua STOKES (Anacardiaceae). It is shown to exert various potent effects such as antioxidant, antiinflammatory induction of apoptosis among many properties. In this study, we investigated the effect of butein on cytokine-induced ß-cell damage. Pre-treatment with butein is shown to increase the viability of cytokine-treated INS-1 cells at concentrations of 15-30 µM. Butein prevented cytokine-mediated cell death, as well as nitric oxide (NO) production, and these effects correlated well with reduced levels of protein expression of the inducible nitric oxide synthase (iNOS). Furthermore, the molecular mechanisms by which butein inhibits iNOS gene expression appeared to be through the inhibition of nuclear factor-κB (NF-κB) translocation. In a second set of experiments, rat islets were used to demonstrate the protective effects of butein and the results were essentially the same as those observed in Beutin pretreated INS-1 cells. Butein prevented cytokine-induced NO production, iNOS expression, and NF-κB translocation and inhibition of glucose-stimulated insulin secretion (GSIS). In conclusion, these results suggest that butein can be used for the prevention of functional ß-cell damage and preventing the progression of Type 1 diabetes mellitus (T1DM).