RESUMEN
Angelicae tenussimae root has been used as a traditional medicine in Asia. Recently, anti-melanogenic and anti-photogenic effects of fermented A. tenuissima root (FAT) were identified. However, information about the anti-atopic dermatitis action of FAT is limited. Thus, the purpose of this study is to determine the applicability of FAT to AD by identifying the efficacy of FAT on the skin barrier and inflammatory response, which are the main pathogenesis of AD. Expression levels of skin barrier components and the production of inflammatory mediators in human keratinocyte and mouse macrophage cells were measured by quantitative RT-PCR or ELISA. FAT upregulated the expression of skin barrier components (filaggrin, involucrin, loricurin, SPTLC1) and inhibited the secretion of an inflammatory chemokine TARC in HaCaT cells. Furthermore, it suppressed pro-inflammatory cytokines (IL-6, TNF-α) and nitric oxide production in LPS-induced RAW264.7 cells. In addition, ligustilide increased filaggrin and SPTLC1, and also lowered pro-inflammatory mediators that increased in atopic environments, such as in FAT results. This means that ligustilide, one of the active ingredients derived from FAT, can ameliorate AD, at least in part, by promoting skin barrier formation and downregulating inflammatory mediators. These results suggest that FAT is a potential functional cosmetic material for the care and management of AD.
Asunto(s)
Aspergillus oryzae , Factor de Necrosis Tumoral alfa , Ratones , Animales , Humanos , Factor de Necrosis Tumoral alfa/metabolismo , Lipopolisacáridos/farmacología , Interleucina-6/metabolismo , Óxido Nítrico/metabolismo , Extractos Vegetales/farmacología , Quimiocinas/metabolismo , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , Piel/metabolismoRESUMEN
Hyperpigmentation is induced by the overactivation of tyrosinase, which is a rate-limiting enzyme in melanogenesis. The defatted extract of hemp (Cannabis sativa L.) seed is known to have inhibitory effects on melanogenesis; however, effective compounds in the extract have not been identified yet. In this study, three phenethyl cinnamamides present in hemp seed extract were prepared by purification and chemical synthesis and were assessed for their inhibitory effect on melanogenesis in B16F10 melanoma cells. A comparison of the anti-melanogenesis and anti-tyrosinase activity of hemp seed solvent fractions revealed that the ethyl acetate fraction possessed the greatest potential for suppressing melanogenesis in melanoma cells by decreasing tyrosinase activity. We tentatively identified 26 compounds in the ethyl acetate fraction by comparing spectroscopic data with the literature. Three phenethyl cinnamamides such as N-trans-caffeoyltyramine, N-trans-coumaroyltyramine, and N-trans-feruloyltyramine present abundantly in the ethyl acetate fraction were prepared and their anti-melanogenesis and anti-tyrosinase activities in melanoma cells were evaluated. We found that N-trans-caffeoyltyramine and N-trans-feruloyltyramine inhibited alpha melanocyte stimulating hormone (α-MSH)-induced melanogenesis without cytotoxicity, while N-trans-coumaroyltyramine inhibited melanogenesis with cytotoxicity. IC50 values of N-trans-caffeoyltyramine, N-trans-feruloyltyramine, and N-trans-coumaroyltyramine for inhibition of α-MSH-mediated tyrosinase activation were 0.8, 20.2, and 6.3 µM, respectively. Overall, N-trans-caffeoyltyramine possessed the strongest anti-melanogenesis activity among the three phenethyl cinnamamides evaluated. The inhibitory effect of N-trans-caffeoyltyramine was verified by determining the melanin content and tyrosinase activity in melanoma after treating the cells with synthetic compounds. Thus, N-trans-caffeoyltyramine isolated from hemp seed extract could be useful in cosmetics as a skin-whitening agent.
RESUMEN
Harmful, stressful conditions or events in the cardiovascular system result in cellular damage, inflammation, and fibrosis. Currently, there is no targeted therapy for myocardial fibrosis, which is highly associated with a large number of cardiovascular diseases and can lead to fatal heart failure. Hydrogen sulfide (H2S) is an endogenous gasotransmitter similar to nitric oxide and carbon monoxide. H2S is involved in the suppression of oxidative stress, inflammation, and cellular death in the cardiovascular system. The level of H2S in the body can be boosted by stimulating its synthesis or supplying it exogenously with a simple H2S donor with a rapid- or slow-releasing mode, an organosulfur compound, or a hybrid with known drugs (e.g., aspirin). Hypertension, myocardial infarction, and inflammation are exaggerated when H2S is reduced. In addition, the exogenous delivery of H2S mitigates myocardial fibrosis caused by various pathological conditions, such as a myocardial infarct, hypertension, diabetes, or excessive ß-adrenergic stimulation, via its involvement in a variety of signaling pathways. Numerous experimental findings suggest that H2S may work as a potential alternative for the management of myocardial fibrosis. In this review, the antifibrosis role of H2S is briefly addressed in order to gain insight into the development of novel strategies for the treatment of myocardial fibrosis.
Asunto(s)
Cardiomiopatías/metabolismo , Diabetes Mellitus/metabolismo , Sulfuro de Hidrógeno/metabolismo , Hipertensión/metabolismo , Infarto del Miocardio/metabolismo , Miocardio/patología , Animales , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/genética , Diabetes Mellitus/enzimología , Diabetes Mellitus/genética , Fibrosis , Humanos , Sulfuro de Hidrógeno/química , Sulfuro de Hidrógeno/farmacología , Sulfuro de Hidrógeno/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/genética , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Deinococcus actinosclerus BM2T (GenBank: KT448814) is a radio-resistant bacterium that is newly isolated from the soil of a rocky hillside in Seoul. As an extremophile, D. actinosclerus BM2T may possess anti-inflammatory properties that may be beneficial to human health. In this study, we evaluated the anti-inflammatory effects of BM2U, an aqueous extract of D. actinosclerus BM2T, on lipopolysaccharide (LPS)-mediated inflammatory responses in RAW264.7 macrophage cells. BM2U showed antioxidant capacity, as determined by the DPPH radical scavenging (IC50 = 349.3 µg/ml) and ORAC (IC50 = 50.24 µg/ml) assays. At 20 µg/ml, BM2U induced a significant increase in heme oxygenase-1 (HO-1) expression (p < 0.05). BM2U treatment (0.2-20 µg/ml) significantly suppressed LPS-induced increase in the mRNA expression of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 (p < 0.05). BM2U treatment also suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which are involved in the production of inflammatory mediators. BM2U treatment also inhibited the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs): JNK, ERK, and p-38 (p < 0.05). Collectively, BM2U exhibited anti-inflammatory potential that can be exploited in attenuating inflammatory responses.
Asunto(s)
Antiinflamatorios/farmacología , Deinococcus/química , Lipopolisacáridos/toxicidad , Animales , Antiinflamatorios/química , Antioxidantes/farmacología , Ciclooxigenasa 2/genética , Citocinas/genética , Deinococcus/aislamiento & purificación , Expresión Génica/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Células RAW 264.7 , Transducción de Señal/efectos de los fármacosRESUMEN
Cheonggukjang and chaga mushrooms have numerous health benefits, and have been used in alternative medicine. Therefore, a powder mixture of 98: Cheonggukjang and 2: Chaga extracts was fermented with Lactobacillus acidophilus KCTC3925 (FCC) and its anti-obesity effects in high-fat diet (HFD)-induced obese mice were determined. Five-week-old male ICR mice were fed a normal diet or HFD in the presence or absence of 3% and 5% FCC by weight (n = 10 per group). After 12 weeks, the mice were sacrificed, and the serum and tissue samples were collected for analysis. Body weight and epididymal fat pad weight were significantly lowered in the 3% and 5% FCC groups compared with those in the HFD control group (p < 0.01). FCC supplementation suppressed serum triglyceride and increased serum HDL-C levels (p < 0.01). Serum GOT, GPT, and leptin levels, hepatic COX-2 mRNA expression, and splenic COX-2 and IL-4 mRNA expression were significantly higher in the HFD groups than in the control group (p > 0.05); however, except for splenic IL-4 levels, the increases were significantly attenuated by FCC supplementation. Expression of ICAM-1, an aortic inflammatory marker, was significantly increased in the HFD group; this effect was suppressed in the 3% FCC group (p < 0.01) but not in the 5% FCC group. FCC suppressed the body weight and epididymal fat pad weight gain, as well as inflammatory responses in the liver and spleen of HFD-fed mice. Thus, FCC supplementation will be beneficial for the treatment of obesity-related effects.
Asunto(s)
Dieta Alta en Grasa/efectos adversos , Alimentos Fermentados , Hígado/efectos de los fármacos , Obesidad/tratamiento farmacológico , Bazo/efectos de los fármacos , Tejido Adiposo , Animales , Peso Corporal , Ciclooxigenasa 2/metabolismo , Fermentación , Lactobacillus acidophilus , Hígado/patología , Masculino , Ratones , Ratones Endogámicos ICR , Ratones Obesos , ARN Mensajero/metabolismo , Bazo/patología , Triglicéridos/sangreRESUMEN
Vascular inflammation has been suggested to play a key role in the initiation and progression of atherosclerosis. Hyperoside (HPS) is a plant-derived quercetin 3-d-galactoside reported to have anti-inflammatory, anti-oxidant, anti-cancer, anti-hyperglycemic, anti-coagulant, and cardioprotective activities. However, the effects of HPS on vascular inflammation have not been studied. Therefore, in this study, we investigated the suppressive effect of HPS on tumor necrosis factor-α (TNFα)-dependent inflammatory responses in MOVAS-1â¯cells, a murine vascular smooth muscle cell (VSMC) line. HPS did not show any significant cytotoxicity up to 10⯵g/mL over 24â¯h. TNFα challenge of VSMCs significantly increased the mRNA (3-fold) and protein expression (20-fold) of vascular cell adhesion molecule-1 (VCAM-1). However, these increases were abolished in the presence of HPS. Additionally, HPS significantly decreased monocyte adhesion to TNFα-stimulated VSMCs in a dose-dependent manner. Further, TNFα challenge induced activation of mitogen-activated protein kinases (MAPKs), such as p38â¯MAPK (38.0⯱â¯3.08 fold), JNK (51.6⯱â¯2.26 fold), and ERK (14.1⯱â¯0.77 fold); expression of nuclear factor-κB (NF-κB; â 4-fold) and TNF receptor 1 (TNFR1; 2.7⯱â¯0.198 fold) were also increased. Notably, the TNFα-induced expression of these molecules was also significantly inhibited by the presence of HPS. Given that p38â¯MAPK, JNK, ERK, NF-κB, and TNFR1 all play regulatory roles in the expression of VCAM-1, this study provides insight into the mechanism of action of HPS. In summary, HPS can inhibit TNFα-mediated vascular inflammatory responses and has potential as a new anti-atherosclerotic drug.
Asunto(s)
Regulación hacia Abajo/efectos de los fármacos , Quercetina/análogos & derivados , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Animales , Adhesión Celular/efectos de los fármacos , Línea Celular , Peroxidación de Lípido/efectos de los fármacos , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Monocitos/citología , Monocitos/efectos de los fármacos , Monocitos/metabolismo , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Quercetina/química , Quercetina/farmacología , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
Angelica tenuissima root has historically been used as a traditional medicine in Korea. Previous studies have identified the anti-melanogenic effects of the extract of A. tenuissima root fermented by Aspergillus oryzae (FAT). This study investigated the protective effects of FAT against ultraviolet light B exposure (UVB; 30 mJ/cm2) in HaCaT (human keratinocyte) or Hs68 (human foreskin fibroblast) skin cells. FAT treatment was able to stimulate wound healing rate at the basal condition. FAT also favored the maintenance and/or improvement of extracellular matrix impairment caused by UVB irradiation through: 1) upregulation of procollagen Type-1 synthesis and secretion; 2) suppression of MMP-1 and elastase expression. FAT was able to play a role in the attenuation of inflammatory responses caused by UVB irradiation via upregulation of photo-protective hemeoxygease-1 and suppression of proinflammatory cyclooxygenase-2 expression. After further verification of the anti-photoaging potential of FAT, it could be utilized as an effective ingredient in anti-aging and anti-wrinkle cosmetics.
Asunto(s)
Angelica/química , Aspergillus oryzae/metabolismo , Alimentos Fermentados , Regulación de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1/genética , Protectores contra Radiación/farmacología , Envejecimiento de la Piel/efectos de los fármacos , Línea Celular Transformada , Movimiento Celular/efectos de los fármacos , Ciclooxigenasa 2/genética , Regulación de la Expresión Génica/efectos de la radiación , Humanos , Queratinocitos/citología , Metaloproteinasa 1 de la Matriz/genética , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Estrés Oxidativo/efectos de la radiación , Elastasa Pancreática/genética , Elastasa Pancreática/metabolismo , Extractos Vegetales/química , Raíces de Plantas/química , Procolágeno/genética , Procolágeno/metabolismo , Rayos Ultravioleta/efectos adversos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Primary osteoporosis is a disease related to excessive bone resorption due to estrogen insufficiency that occurs postmenopause. Protocatechuic acid (PCA), or 3,4-dihydroxybenzoic acid, is a common compound present in numerous plants. Although numerous biological activities of PCA have been identified, its antiosteoporotic function has not been well established. In this study, the antiosteoporotic activity of PCA supplementation was determined in ovariectomized (OVX) female ICR mice at 12 weeks after OVX. The biomechanical properties of a bone were evaluated by microcomputed tomography. The signaling molecules associated with osteoclast differentiation were determined in bone marrow cells through immunoblot or RT-PCR. Oral supplementation with PCA (20 mg/kg/day) significantly ameliorated the OVX-mediated stimulation of osteoclast activity based on decreases in serum levels of receptor activator of nuclear factor κB ligand (RANKL), osteocalcin, and bone alkaline phosphatase and increase in serum osteoprotegerin (each group, n = 6; p < 0.05). In addition, the OVX-induced decreases in mRNA expression levels of cathepsin K, calcitonin receptor, nuclear factor of activated T cell cytoplasmic 1 (NFATc1), and tumor necrosis factor (TNF) receptor-associated factor-6 (TRAF6) in bone marrow cells were significantly attenuated (each group, n = 6; p < 0.05). Finally, the loss of trabecular bone and changes in biomechanical properties of a bone were significantly improved by supplementation with 20 mg/kg PCA (each group, n = 6; p < 0.05). Collectively, our results show that PCA supplement suppressed trabecular bone loss in OVX mice and therefore might be an effective alternative approach for preventing the progression of postmenopausal osteoporosis.
Asunto(s)
Hueso Esponjoso/patología , Hidroxibenzoatos/uso terapéutico , Ovariectomía/efectos adversos , Animales , Femenino , Humanos , Hidroxibenzoatos/farmacología , RatonesRESUMEN
The anti-melanogenic effects of the extract of Angelica tenuissima (AT) root and the extract of AT root fermented by Aspergillus oryzae (FAT) were investigated. These effects were determined by measuring the inhibitory activity of AT and FAT on melanin production in B16F10 melanocytes and with in vitro tyrosinase activity assays. The AT extract inhibited melanin production at concentrations above 250 µg/ml, and this inhibitory effect was significantly enhanced by the fermentation process with A. oryzae. HPLC analysis resulted in the isolation of two active compounds from both the AT and FAT extracts. Their chemical structures were identified as decursin and Z-ligustilide through comparison with previously reported NMR data. The decursin and Z-ligustilide contents were increased in the FAT extract and could be responsible for its enhanced inhibitory effects on melanin production and tyrosinase activity compared with that of the AT extract.
Asunto(s)
4-Butirolactona/análogos & derivados , Angelica/química , Aspergillus oryzae/metabolismo , Benzopiranos/farmacología , Butiratos/farmacología , Extractos Vegetales/farmacología , Raíces de Plantas/química , Plantas Medicinales/química , 4-Butirolactona/química , 4-Butirolactona/aislamiento & purificación , 4-Butirolactona/metabolismo , 4-Butirolactona/farmacología , Angelica/microbiología , Animales , Benzopiranos/química , Benzopiranos/aislamiento & purificación , Benzopiranos/metabolismo , Butiratos/química , Butiratos/aislamiento & purificación , Butiratos/metabolismo , Técnicas de Cultivo de Célula , Línea Celular/efectos de los fármacos , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Fermentación , Alimentos Fermentados , Melaninas/metabolismo , Melanocitos/efectos de los fármacos , Melanoma Experimental/tratamiento farmacológico , Ratones , Monofenol Monooxigenasa/análisis , Extractos Vegetales/química , Raíces de Plantas/microbiología , Plantas Medicinales/microbiologíaRESUMEN
Amyloid ß (Aß) deposition is a hallmark of Alzheimer's disease (AD). Vascular modifications, including altered brain endothelial cell function and structural viability of the blood-brain barrier due to vascular pulsatility, are implicated in AD pathology. Pulsatility of phenomena in the cerebral vasculature are often not considered in in vitro models of the blood-brain barrier. We demonstrate, for the first time, that pulsatile stretch of brain vascular endothelial cells modulates amyloid precursor protein (APP) expression and the APP processing enzyme, ß-secretase 1, eventuating increased-Aß generation and secretion. Concurrent modulation of intercellular adhesion molecule 1 and endothelial nitric oxide synthase (eNOS) signaling (expression and phosphorylation of eNOS) in response to pulsatile stretch indicates parallel activation of endothelial inflammatory pathways. These findings mechanistically support vascular pulsatility contributing towards cerebral Aß levels.
Asunto(s)
Enfermedad de Alzheimer/patología , Precursor de Proteína beta-Amiloide/análisis , Técnicas Citológicas/métodos , Células Endoteliales/patología , Pulso Arterial , Secretasas de la Proteína Precursora del Amiloide/análisis , Ácido Aspártico Endopeptidasas/análisis , Células Cultivadas , Perfilación de la Expresión Génica , Humanos , Molécula 1 de Adhesión Intercelular/análisis , Modelos Biológicos , Óxido Nítrico Sintasa de Tipo III/análisis , Estrés MecánicoRESUMEN
Isoflavone itself is less available in the body without the aid of intestinal bacteria. In this study, we searched for isoflavone-transforming bacteria from human fecal specimens (n = 14) using differential selection media. Isoflavone-transforming activity as the production of dihydrogenistein and dihydrodaidzein was assessed by high-performance liquid chromatography and we found Lactobacillus rhamnosus, named L. rhamnosus vitaP1, through 16S rDNA sequence analysis. Extract from Pueraria lobata (EPL) and soy hypocotyl extract were fermented with L. rhamnosus vitaP1 for 24 and 48 h at 37°C. Fermented EPL (FEPL) showed enhanced anti-tyrosinase activity and antioxidant capacities, important suppressors of the pigmentation process, compared with that of EPL (p < 0.05). At up to 500 µg/ml of FEPL, there were no significant cell cytotoxicity and proliferation on B16-F10 melanoma cells. FEPL (100 µg/ml) could highly suppress the content of melanin and melanosome formation in B16-F10 cells. In summary, Lactobacillus rhamnosus vitaP1 was found to be able to biotransform isoflavones in EPL. FEPL showed augmented anti-melanogenic potential.
Asunto(s)
Isoflavonas/metabolismo , Lacticaseibacillus rhamnosus/metabolismo , Extractos Vegetales/metabolismo , Pueraria/química , Antioxidantes/análisis , Biotransformación , Cromatografía Líquida de Alta Presión , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Inhibidores Enzimáticos/análisis , Heces/microbiología , Fermentación , Humanos , Lacticaseibacillus rhamnosus/clasificación , Lacticaseibacillus rhamnosus/genética , Lacticaseibacillus rhamnosus/aislamiento & purificación , Melaninas/antagonistas & inhibidores , Monofenol Monooxigenasa/antagonistas & inhibidores , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Glycine max/química , Temperatura , Factores de TiempoRESUMEN
Atherosclerosis is a chronic inflammatory disease, and the increased expression of adhesion molecules on vascular smooth muscle cells contributes to the progression of vascular disease. Quinic acid (QA) has been shown to possess radioprotection, anti-neuroinflammatory, and anti-oxidant activities; however, an anti-vascular inflammatory effect has not been reported. This study investigated the effect of QA on the expression of vascular cell adhesion molecule-1 (VCAM-1) stimulated by TNF-α in MOVAS cells. Pre-incubation of MOVAS cells, the mouse vascular smooth muscle cell line for 2h with QA (0.1, 1 and 10 µg/mL) dose-dependently inhibits TNF-α-induced mRNA and protein expression of VCAM-1 and monocyte adhesion. QA inhibits TNF-α-stimulated phosphorylation of MAP kinase and NK-κB activation. Our results indicate that QA inhibits the TNF-α-stimulated induction of VCAM-1 in VSMC by inhibiting the MAP kinase and NF-κB signaling pathways and the adhesion capacity of VSMC, which may explain the ability of QA to inhibit vascular inflammation such as atherosclerosis.
Asunto(s)
Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Ácido Quínico/farmacología , Factor de Necrosis Tumoral alfa/toxicidad , Molécula 1 de Adhesión Celular Vascular/antagonistas & inhibidores , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Inflamación/prevención & control , Ratones , Ácido Quínico/uso terapéutico , Molécula 1 de Adhesión Celular Vascular/biosíntesisRESUMEN
Nephrotoxicity is a main problem in cancer patients using cisplatin. Oxidative stress, inflammation and apoptosis are the important mechanisms of cisplatin induced nephrotoxicity. In the present study, we investigated the effect of the extracts of morning glory on nephrotoxicity by cisplatin in human embryonic kidney cells 293 (HEK-293) and mice. Previous studies have reported that morning glory extracts showed potent activity on anti-inflammatory and anti-oxidant. However, the protective effects of the n-hexane layer of morning glory seed (MGs-Hx) on nephrotoxicity and its mechanisms have not been clearly understood. Oral administration with MGs-Hx showed protective effects in vivo experiments test and the treatment of MGs-Hx in a concentration of 100mg/kg/day had significant effect both of decreasing serum creatinine, BUN, serum uric acid level and reduced iNOS, COX-2 mRNA expressions with low side-effect. Moreover, cell viability was restored by MGs-Hx treatment compared to cisplatin-induced nephrotoxic HEK-293 cells. Co-treatment with MGs-Hx and cisplatin showed the significant effect to reduce inflammatory enzyme, iNOS expression and continuous production of NO. In addition, it exhibited a tendency to decreasing expression of apoptosis-related proteins, caspase-3, 8 and 9, and NF-κB translocation to nucleus as well as phosphorylation of p38, JNK, ERK in cisplatin-induced nephrotoxic HEK-293 cells. Our study provides insight into the underlying mechanisms of MGs-Hx and suggests that MGs-Hx might be a potential therapeutic agent to modulate inflammation and apoptosis in nephrotoxicity.
Asunto(s)
Antiinflamatorios/farmacología , Cisplatino/toxicidad , Ipomoea nil/química , Enfermedades Renales/prevención & control , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Antineoplásicos/toxicidad , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Etanol/química , Células HEK293 , Hexanos/química , Humanos , Inflamación/inducido químicamente , Inflamación/prevención & control , Enfermedades Renales/inducido químicamente , Masculino , Ratones , Ratones Endogámicos ICR , Estrés Oxidativo/efectos de los fármacos , SemillasRESUMEN
Atherosclerosis is a complex inflammatory disease associated with elevated levels of atherogenic molecules for leukocyte recruitment. Sinigrin (2-propenylglucosinolate) is found mainly in broccoli, brussels sprouts, and black mustard seeds. Recently, sinigrin has received attention for its role in disease prevention and health promotion. In this study, we examined the effect of sinigrin on development of atherosclerosis in ApoE-/- mice and the expression of adhesion molecules in vascular smooth muscle cells (VSMCs). The serum concentrations of lactate dehydrogenase (LDH), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), calcium (Ca2+), and pro-inflammatory cytokines were reduced by sinigrin treatment in ApoE-/- mice. In addition, oral administration of sinigrin attenuated the mRNA expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), C-C motif chemokine ligand 2 (CCL2), and CCL5 on aorta tissues and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), liver X receptor (LXR), sterol regulatory element-binding protein-2 (SREBP-2), and low density lipoprotein receptor (LDLR) on liver tissues in ApoE-/- mice. To provide a potential mechanism underlying the action of sinigrin, we evaluated the in vitro effect of sinigrin on the expression of the VCAM-1 in TNF-α-induced VSMCs. The increased expression of VCAM-1 by TNF-α stimulation was significantly suppressed by the treatment of sinigrin (1-100 µg/ml) and sinigrin inhibited the nuclear translocation of NF-κB and the phosphorylation of p38 MAPK and JNK pathways, suggesting that sinigrin decreases the TNF-α-stimulated VCAM-1 expression through the suppression of NF-κB and MAP kinases signaling pathways. Overall, sinigrin has the potential to be used in reducing the risks of atherosclerosis.
Asunto(s)
Aterosclerosis/prevención & control , Dieta Alta en Grasa , Expresión Génica/efectos de los fármacos , Glucosinolatos/farmacología , Molécula 1 de Adhesión Celular Vascular/metabolismo , Animales , Aorta/diagnóstico por imagen , Aorta/metabolismo , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Aterosclerosis/patología , Quimiocina CCL2/metabolismo , Quimiocina CCL5/metabolismo , Progresión de la Enfermedad , Glucosinolatos/uso terapéutico , Molécula 1 de Adhesión Intercelular/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Lipoproteínas LDL/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Molécula 1 de Adhesión Celular Vascular/análisis , Molécula 1 de Adhesión Celular Vascular/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
The hepatic anti-inflammatory potential of hexane extracts of Dioscorea batatas Decne edible part (EDH-1e) and bark (EDH-2b) were investigated in Western-type diet-fed apolipoprotein E null [ApoE (-/-)] mice and HepG2 cells. EDH-1e and EDH-2b suppressed the increased levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, transforming growth factor beta 1 (TGF-ß1), vascular cell adhesion protein 1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1), and reduced infiltration of monocytes into liver tissue. The protein levels of Toll-like receptor 4 (TLR4) were also downregulated by EDH-1e and EDH-2b treatment as were the levels of activator protein 1 (AP-1), c-fos, and c-jun in the livers from Western-type diet-fed ApoE (-/-) mice and in lipopolysaccharide-stimulated HepG2 cells. Taken together, EDH-1e and EDH-2b attenuated hepatic inflammation and fibrosis via suppression of the TLR4-AP1-mediated signaling pathway.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Dioscorea/química , Hepatocitos/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/antagonistas & inhibidores , Animales , Dieta Occidental/efectos adversos , Etnofarmacología , Células Hep G2 , Hepatocitos/inmunología , Hepatocitos/metabolismo , Hepatocitos/patología , Hexanos/química , Humanos , Masculino , Medicina Tradicional Coreana , Ratones Endogámicos C57BL , Ratones Noqueados , Monocitos/efectos de los fármacos , Monocitos/inmunología , Monocitos/metabolismo , Monocitos/patología , Enfermedad del Hígado Graso no Alcohólico/inmunología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Corteza de la Planta/química , Rizoma/química , Solventes/química , Receptor Toll-Like 4/metabolismo , Factor de Transcripción AP-1/antagonistas & inhibidores , Factor de Transcripción AP-1/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Dravet syndrome is a rare and severe type of epilepsy in infants. The heterogeneity in the overall intellectual disability that these patients suffer from has been attributed to differences in genetic background and epilepsy severity. METHODS: Eighteen Vietnamese children diagnosed with Dravet syndrome were included in this study. SCN1A variants were screened by direct sequencing and multiplex ligation-dependent probe amplification. Adaptive functioning was assessed in all patients using the Vietnamese version of the Vineland Adaptive Behavior Scales, and the results were analyzed relative to the SCN1A variants and epilepsy severity. RESULTS: We identified 13 pathogenic or likely pathogenic variants, including 6 that have not been reported previously. We found no correlations between the presence or type of SCN1A variants and the level of adaptive functioning impairment or severity of epilepsy. Only two of nine patients aged at least 5 years had an adaptive functioning score higher than 50. Both of these patients had a low frequency of convulsive seizures and no history of status epilepticus or prolonged seizures. The remaining seven had very low adaptive functioning scores (39 or less) despite the variability in the severity of their epilepsy confirming the involvement of factors other than the severity of epilepsy in determining the developmental outcome. CONCLUSIONS: Our study expands the spectrum of known SCN1A variants and confirms the current understanding of the role of the genetic background and epilepsy severity in determining the developmental outcome of Dravet syndrome patients.
RESUMEN
Excessive consumption of fat and fructose augments the pathological progression of nonalcoholic fatty liver disease through hepatic fibrosis, inflammation, and hepatic de novo lipogenesis. We hypothesized that supplementation with Cynanchum wilfordii extract (CWE) decreases fat accumulation in the liver by suppressing cyclooxygenase-2 (COX-2), the nuclear translocation of nuclear factor κB (NF-κB), and p38 mitogen-activated protein kinase (MAPK). The beneficial effect of CWE was evaluated in a murine model of nonalcoholic fatty liver disease. Mice were fed either a normal diet or an atherogenic diet with fructose (ATHFR) in the presence or absence of CWE (50, 100, or 200 mg/kg; n=6/group). Treatment with ATHFR induced a hepatosplenomegaly-like condition (increased liver and spleen weight); this pathological change was attenuated in the presence of CWE. The ATHFR group exhibited impaired liver function, as evidenced by increased blood levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, fat accumulation in the liver, and lipid profiles. Supplementation of CWE (100 and 200 mg/kg, P<.05) ameliorated these impaired liver functions. Atherogenic diet with fructose increased the protein levels of COX-2 and p38 MAPK, as well as the nuclear translocation of NF-κB. These signaling pathways, which are associated with the inflammatory response, were markedly suppressed after CWE treatment (100 and 200 mg/kg). In summary, CWE supplementation reduced high-fat and high-fructose diet-induced fat accumulation and damage in the liver by suppressing COX-2, NF-κB, and p38 MAPK.
Asunto(s)
Ciclooxigenasa 2/metabolismo , Cynanchum , Dieta Alta en Grasa/efectos adversos , Fructosa/efectos adversos , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/efectos adversos , Azúcares de la Dieta/administración & dosificación , Azúcares de la Dieta/efectos adversos , Suplementos Dietéticos , Modelos Animales de Enfermedad , Conducta Alimentaria , Inflamación/metabolismo , Inflamación/prevención & control , Lipogénesis/efectos de los fármacos , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Raíces de Plantas , Transducción de SeñalRESUMEN
This study determined the anti-obesity effect of Crinum asiaticum var. japonicum Baker extract (CAE) on adipocytes and obese mice. The inhibitory effects of CAE on adipocyte differentiation and adipogenesis were determined using differentiation induction medium in 3T3-L1 cells. To get an insight into underlying molecular actions of CAE, we investigated the changes in the expression levels of genes involved in lipogenesis by CAE treatment using qRT-PCR. CAE strongly suppressed adipocyte differentiation through downregulation of PPARγ, C/EBPα, C/EBP ß, and aP2. CAE treatment could also suppress the expression levels of ACC, FAS, LPL and HMGCR gene in 3T3-L1 cells. Male C57BL/6 strain and C57BL/6J-ob/ob strain mice were fed with HFD containing 60% fat and normal diet in the presence or absence of 25, 50, and 100mg/kg CAE for 7 weeks. CAE supplementation could highly suppress the body weight gain and epididymal fat accumulation without changes in food uptake in both obese models. Increases in total cholesterol, LDL-cholesterol and triglyceride were highly suppressed in the presence of CAE. In summary, CAE has an anti-obesity effect and this anti-obesity potential might be associated with downregulation of genes involved in adipocyte differentiation and lipogenesis.
Asunto(s)
Crinum/química , Dieta Alta en Grasa/efectos adversos , Obesidad/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipogénesis/efectos de los fármacos , Adipogénesis/genética , Animales , Peso Corporal/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Conducta Alimentaria/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Gotas Lipídicas/metabolismo , Lípidos/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/sangre , Obesidad/patología , Tamaño de los Órganos/efectos de los fármacos , PPAR gamma/metabolismo , Fitoterapia , Extractos Vegetales/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Transcripción/metabolismo , Aumento de Peso/efectos de los fármacosRESUMEN
The antiallergic potential of Arctium lappa L. was investigated in Sprague-Dawley rats, ICR mice, and RBL-2H3 cells. Ethanol extract (90%) of A. lappa (ALE, 100 µg/mL) inhibited the degranulation rate by 52.9%, determined by the level of ß-hexosaminidase. ALE suppressed passive cutaneous anaphylaxis (PCA) in rats and attenuated anaphylaxis and histamine release in mice. To identify the active compound of ALE, we subsequently fractionated and determined the level of ß-hexosaminidase in all subfractions. Oleamide was identified as an active compound of ALE, which attenuated the secretion of histamine and the production of tumor necrosis factor (TNF)-α and interleukin-4 (IL-4) in cells treated with compound 48/80 or A23187/phorbol myristate acetate (PMA). Oleamide suppressed FcεRI-tyrosine kinase Lyn-mediated pathway, c-Jun N-terminal kinases (JNK/SAPK), and p38 mitogen-activated protein kinases (p38-MAPKs). These results showed that ALE and oleamide attenuated allergic reactions and should serve as a platform to search for compounds with antiallergic activity.
Asunto(s)
Antialérgicos/administración & dosificación , Arctium/química , Hipersensibilidad/tratamiento farmacológico , Ácidos Oléicos/administración & dosificación , Extractos Vegetales/administración & dosificación , Receptores de IgE/inmunología , Animales , Antialérgicos/aislamiento & purificación , Línea Celular , Histamina/inmunología , Humanos , Hipersensibilidad/inmunología , Interleucina-4/inmunología , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Ratones , Ratones Endogámicos ICR , Quinasas de Proteína Quinasa Activadas por Mitógenos/inmunología , Ácidos Oléicos/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc (Zn(2+)) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of Zn(2+) activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular Zn(2+) levels are largely regulated by metallothioneins (MTs), Zn(2+) importers (ZIPs), and Zn(2+) transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of Zn(2+). However, these regulatory actions of Zn(2+) are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular Zn(2+) levels, Zn(2+)-mediated signal transduction, impacts of Zn(2+) on ion channels and mitochondrial metabolism, and finally, the implications of Zn(2+) in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of Zn(2+).