RESUMO
Ginseng (Panax ginseng Meyer) is a well-known herbal medicine that has been used for a long time in Korea to treat various diseases. This study investigated the in vitro and in vivo protective effects of red ginseng extract (RGE) and red ginseng oil (RGO). Liver injury was produced in BALB/c mice by 400 mg/kg of acetaminophen intraperitoneal injection. The antioxidant effects of RGE and RGO on the free radicals 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) were measured. In addition, the hepatoprotective activities of RGE and RGO on liver markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and oxidative stress markers, including superoxide dismutase (SOD), catalase (CAT) enzyme activity, and 8-hydroxy-2-deoxyguanosine (8-OHdG) in serum and histopathological analysis, were evaluated. The protective effect of RGO on UV-induced phototoxicity was also evaluated in Balb/c 3T3 mouse fibroblast cell line. RGE and RGO effectively inhibited the radicals DPPH and ABTS compared with ascorbic acid and trolox, respectively. Moreover, RGE and RGO significantly decreased the liver enzyme (ALT and AST) levels, increased the antioxidant enzyme (SOD and CAT) levels, and decreased the DNA oxidation product (8-OHdG) content in mice serum. RGO also exhibited protective effect against UV irradiation compared with chlorpromazine hydrochloride, a known phototoxic drug, in Balb/c 3T3 cell line. RGE and RGO possess antioxidant and hepatoprotective properties in mice, and RGO exerts nonphototoxic activity in Balb/c 3T3 cells.
Assuntos
Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Panax/metabolismo , Extratos Vegetais/farmacologia , Raios Ultravioleta/efeitos adversos , Animais , Antioxidantes/metabolismo , Ácido Ascórbico/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Glutationa/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos BALB C , Fitoterapia/métodos , Plantas Medicinais/metabolismoRESUMO
BACKGROUND: Depression is a serious and common psychiatric disorder generally affecting more women than men. A woman's risk of developing depression increases steadily with age, and higher incidence is associated with the onset of menopause. Here we evaluated the antidepressant properties of Asparagus cochinchinensis (AC) extract and investigated its underlying mechanisms in a rat menopausal depression model. METHODS: To model this menopausal depression, we induced a menopause-like state in rats via ovariectomy and exposed them to chronic unpredictable mild stress (CUMS) for 6 weeks, which promotes the development of depression-like symptoms. During the final 4 weeks of CUMS, rats were treated with either AC extract (1000 or 2000 mg/kg, PO), which has been reported to provide antidepressant effects, or with the tricyclic antidepressant imipramine (10 mg/kg, IP). RESULTS: We report that CUMS promotes depression-like behavior and significantly increases serum corticosterone and inflammatory cytokine levels in the serum of ovariectomized (OVX) rats. We also found that CUMS decreases the expression of brain-derived neurotrophic factor (BDNF) and its primary receptor, tropomyosin receptor kinase B (TrkB), in OVX rats, and treatment with AC extract rescues both BDNF and TrkB expression levels. CONCLUSION: These results suggest that AC extract exerts antidepressant effects, possibly via modulation of the BDNF-TrkB pathway, in a rat model of menopausal depression.
Assuntos
Antidepressivos/farmacologia , Asparagus , Depressão/tratamento farmacológico , Menopausa , Extratos Vegetais/farmacologia , Estresse Psicológico/tratamento farmacológico , Animais , China , Modelos Animais de Doenças , Feminino , Ovariectomia , Raízes de Plantas , Ratos , Ratos WistarRESUMO
PURPOSE: Recent studies have reported the anti-inflammatory effect of Sinomenium acutum. We investigated the anti-inflammatory effect of sinomenine on endotoxin-induced uveitis in a rat model. METHODS: Endotoxin-induced uveitis was induced in rat by lipopolysaccharide (LPS) immunization. Sinomenine (50mg/kg and 100mg/kg) was administered at 30 minutes before, 6 hours and 12 hours after LPS immunization. Clinical and histological severity was evaluated. Protein concentration and levels of tumor necrosis factor (TNF)-α and prostaglandin (PG)-E2 in aqueous humor were measured. Expression of activated Nuclear factor (NF)-κB p65 in ciliary body was also observed. RESULTS: Clinical and histological severities were significantly milder in sinomenine-treated rat than in controls (P < 0.001). Sinomenine suppressed protein leakage and down-regulated the production of TNF-α and PG-E2 in a dose-dependent manner. Sinomenine treatment suppressed the translocation of the NF-κB p65 subunit into the nuclei. CONCLUSION: Systemic administration of sinomenine suppressed the inflammation of ocular tissues. These findings suggest that sinomenine could be a novel therapeutic agent for the control of endogenous ocular inflammatory disease.
Assuntos
Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Sinomenium , Uveíte/tratamento farmacológico , Animais , Humor Aquoso , Modelos Animais de Doenças , Endotoxinas , Lipopolissacarídeos , Masculino , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Ratos , Ratos Endogâmicos Lew , Fator de Necrose Tumoral alfa , Uveíte/imunologiaRESUMO
Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with complex pathophysiology involving the brain-gut axis. To assess the effects of Wasabia koreana (WK) on IBS, we employed a mouse model of colonic zymosan injection presenting with diarrhea-predominant IBS-like symptoms. Oral WK administration significantly diminished stool score, suppressed colon length and weight change, and minimized body weight loss without affecting food intake. In WK-treated mice, the submucosal thickening and epithelial lining of the colon were inhibited and were similar to those of naïve mice. Infiltration of mast cells into the colon and serum tumor necrosis factor-α levels were markedly suppressed. These effects were comparable to those of sulfasalazine, an anti-inflammatory drug. Furthermore, the number of visceral pain-related behaviors was significantly decreased, and locomotion activities measured in the elevated plus maze and open field tests were significantly increased by WK in a dose-dependent manner compared with amitriptyline, an antidepressant. These changes were accompanied by reduced FosB2 expression in the brain. Taken together, these data suggest that WK may have potential as a medicinal food for IBS by acting on inflammatory diarrhea and neural activity.
Assuntos
Síndrome do Intestino Irritável/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Wasabia/química , Zimosan/efeitos adversos , Animais , Colo/efeitos dos fármacos , Colo/imunologia , Modelos Animais de Doenças , Humanos , Síndrome do Intestino Irritável/induzido quimicamente , Síndrome do Intestino Irritável/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/análise , Fator de Necrose Tumoral alfa/imunologiaRESUMO
OBJECTIVE: The purpose of the present study was to investigate the usefulness of 457 and 473 nm lasers for the curing of composite resins during the restoration of damaged tooth cavity. BACKGROUND DATA: Monochromaticity and coherence are attractive features of laser compared with most other light sources. Better polymerization of composite resins can be expected. MATERIALS AND METHODS: Eight composite resins were light cured using these two lasers and a light-emitting diode (LED) light-curing unit (LCU). To evaluate the degrees of polymerization achieved, polymerization shrinkage and flexural and compressive properties were measured and compared. RESULTS: Polymerization shrinkage values by 457 and 473 nm laser, and LED ranged from 10.9 to 26.8, from 13.2 to 26.1, and from 11.5 to 26.3 µm, respectively. The values by 457 nm laser was significantly different from those by 473 and LED LCU (p<0.05). However, there was no statistical difference between values by 473 and LED LCU. Before immersion in distilled water, flexural strength (FS) and compressive modulus (CM) of the specimens were inconsistently influenced by LCUs. On the other hand, flexural modulus (FM) and compressive strength (CS) were not significantly different for the three LCUs (p>0.05). For the tested LCUs, no specific LCU could consistently achieve highest strength and modulus from the specimens tested. CONCLUSIONS: Two lasers (457 and 473 nm) can polymerize composite resins to the level that LED LCU can achieve despite inconsistent trends of polymerization shrinkage and flexural and compressive properties of the tested specimens.
Assuntos
Resinas Compostas/efeitos da radiação , Lâmpadas de Polimerização Dentária , Terapia com Luz de Baixa Intensidade , Polimerização/efeitos da radiaçãoRESUMO
PURPOSE: To examine the association between female reproductive factors and age-related macular degeneration (AMD) in postmenopausal women. DESIGN: Nationwide population-based cross-sectional study. METHODS: A nationally representative dataset acquired from the 2010-2012 Korea National Health and Nutrition Examination Survey was analyzed. The dataset involved information for 4,377 postmenopausal women aged ≥50 years with a fundus photograph evaluable for AMD in either eye. All participants were interviewed using standardized questionnaires to determine reproductive factors including menstruation, pregnancy, parity, lactation, and hormonal use. The association between reproductive factors and each type of AMD was investigated. RESULTS: The mean age of the study participants was 63.1±0.2 years. Mean ages at menarche and menopause were 16.1±0.0 and 49.2±0.1 years, respectively. The overall prevalence rates of early and late AMD were 11.2% (95% confidence interval [CI], 10.1-12.5) and 0.8% (95% CI, 0.5-1.2), respectively. When adjusted for age, neither smoking nor alcohol use was associated with the presence of any AMD or late AMD. Multivariate logistic regression analysis revealed age (OR, 1.12 per 1 year), duration of lactation (OR, 0.91 per 6 months), and duration of use of oral contraceptive pills (OCP) (OR, 1.10 per 6 months) as associated factors for late AMD. The other variables did not yield a significant correlation with the risk of any AMD or late AMD. CONCLUSION: After controlling for confounders, a longer duration of lactation appeared to protect against the development of late AMD. A longer duration of OCP use was associated with a higher risk of late AMD.
Assuntos
Degeneração Macular/epidemiologia , Paridade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Degeneração Macular/etiologia , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Inquéritos Nutricionais , Pós-Menopausa , Prevalência , República da Coreia , Fatores de RiscoRESUMO
BACKGROUND: Blood-brain barrier (BBB) disruption mediated by proteases plays a pivotal role in neural tissue damage after acute ischemic stroke. In an animal stroke model, the activation of matrix metalloproteinases (MMPs), especially MMP-9, was significantly increased and it showed potential association with blood-brain barrier (BBB) disruption and cerebral edema. Theoretically, it is expected that early blockade of expression and activation of MMP-9 after ischemic stroke provides neuroprotective effects from secondary neural tissue damage. This study was aimed to determine the ability of rutin to influence MMP-9 expression, activity and BBB disruption using a photothrombotic focal ischemic model in rats. METHODS: Adult male Sprague-Dawley rats, weighing between 250 and 300 g (aged 8 weeks) received focal cerebral ischemia by photothrombosis using Rose Bengal (RB) and cold light. Injured animals were divided into two groups; one group received 50mg/kg of rutin intraperitoneally, starting 1h after injury and at 12h intervals for 3 days, while animals in the control group received weight-adjusted doses of saline vehicle over the same period. In each group, the expressions and activities of MMP-9 were assessed by Western blot and gelatin zymography at 6, 24, 48, and 72 h after photothrombotic insult. The effects of rutin on BBB disruption and functional outcomes were also determined. RESULTS: Western blot and zymographic analysis showed up-regulated MMP-9 expression and activity in the ischemic cortex. The expression and activity of MMP-9 were significantly elevated at 6h after photothrombotic insult, which remained up-regulated for at least until 72 h after injury. In the rutin-treated group, MMP-9 expression and activity were significantly attenuated at 6, 24, and 48 h compared to the control group. Relative to the control group, BBB permeability was significantly reduced in the rutin-treated group. The results of the rotarod test revealed that rutin treatment significantly improved functional outcomes. CONCLUSIONS: Rutin treatment starting 1h after injury attenuated BBB disruption during photothrombotic focal ischemia, which was partly, at least, achieved through inhibitory effects on MMP-9 expression and activity. The results of this study suggest that rutin might be useful in clinical trials aimed to improve the outcome of patients suffering from acute ischemic stroke.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Modelos Animais de Doenças , Trombose Intracraniana/tratamento farmacológico , Metaloproteinase 9 da Matriz/biossíntese , Estimulação Luminosa/efeitos adversos , Rutina/uso terapêutico , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/enzimologia , Isquemia Encefálica/enzimologia , Isquemia Encefálica/etiologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Trombose Intracraniana/enzimologia , Trombose Intracraniana/etiologia , Masculino , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Rosa Bengala/toxicidade , Rutina/farmacologia , Resultado do TratamentoRESUMO
Elevation of amyloid ß-peptide (Aß) is critically associated with Alzheimer disease (AD) pathogenesis. Aß-induced synaptic abnormalities, including altered receptor trafficking and synapse loss, have been linked to cognitive deficits in AD. Recent work implicates a lipid critical for neuronal function, phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2], in Aß-induced synaptic and behavioral impairments. Synaptojanin 1 (Synj1), a lipid phosphatase mediating the breakdown of PI(4,5)P2, has been shown to play a role in synaptic vesicle recycling and receptor trafficking in neurons. Heterozygous deletion of Synj1 protected neurons from Aß-induced synaptic loss and restored learning and memory in a mouse model of AD. Thus, inhibition of Synj1 may ameliorate Aß-associated impairments, suggesting Synj1 as a potential therapeutic target. To this end, we developed a screening assay for Synj1 based on detection of inorganic phosphate liberation from a water-soluble, short-chain PI(4,5)P2. The assay displayed saturable kinetics and detected Synj1's substrate preference for PI(4,5)P2 over PI(3,4,5)P3. The assay will enable identification of novel Synj1 inhibitors that have potential utility as chemical probes to dissect the cellular role of Synj1 as well as potential to prevent or reverse AD-associated synaptic abnormalities.
Assuntos
Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores Enzimáticos/farmacologia , Proteínas do Tecido Nervoso/antagonistas & inibidores , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Linhagem Celular , Ativação Enzimática/efeitos dos fármacos , Expressão Gênica , Genes Reporter , Proteínas de Fluorescência Verde/genética , Ensaios de Triagem em Larga Escala , Humanos , Proteínas Recombinantes de Fusão , Reprodutibilidade dos Testes , Bibliotecas de Moléculas Pequenas , Especificidade por SubstratoRESUMO
PURPOSE: To compare the efficacy and safety between low-fluence photodynamic therapy (PDT) and the intravitreal ranibizumab in the treatment of chronic central serous chorioretinopathy (CSC). DESIGN: Prospective, randomized, single-center, parallel-arm, controlled trial. PARTICIPANTS: Thirty-four eyes of 32 patients with chronic CSC with >6 months' duration of symptoms or recurrent CSC were randomly placed into the low-fluence PDT group (n = 18) or the ranibizumab group (n = 16). INTERVENTION: The patients underwent a single session of low-fluence PDT or 3 consecutive monthly injections of ranibizumab. Rescue treatment was available from month 3 if the subretinal fluid (SRF) persisted or recurred after primary treatment; low-fluence PDT was given to the ranibizumab group and intravitreal ranibizumab to the low-fluence PDT group. MAIN OUTCOME MEASURES: The primary outcome was the proportion of eyes with complete resolution of SRF without rescue treatment. Secondary outcomes included the mean changes in logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA), central retinal thickness (CRT), and angiographic findings from baseline to 12 months. RESULTS: At month 12, 16 eyes (88.9%) of the low-fluence PDT group maintained complete resolution of SRF without rescue treatment versus 2 eyes (12.5%) in the ranibizumab group (P <0.001). Two eyes (11.1%) in the low-fluence PDT group and 11 eyes (68.8%) in the ranibizumab group met the criteria for rescue treatment (P = 0.001). In the low-fluence PDT group, the mean decrease in CRT from baseline was significantly greater than that in the ranibizumab group until month 6 (P <0.05), but the differences became insignificant thereafter. The improvement in BCVA from baseline was superior in the low-fluence PDT group to that in the ranibizumab group, but the differences were not statistically significant except at month 3 (P = 0.025). On indocyanine green angiography, a significantly greater proportion of the low-fluence PDT group (16 eyes; 88.9%) showed a marked reduction in choroidal hyperpermeability after primary treatment than that of the ranibizumab group (0 eyes; P <0.001). No serious adverse events related to the drugs or procedures were observed. CONCLUSIONS: This study represents the overall superiority of low-fluence PDT compared with intravitreal ranibizumab in the treatment of chronic CSC.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Coriorretinopatia Serosa Central/tratamento farmacológico , Terapia com Luz de Baixa Intensidade , Fotoquimioterapia , Adulto , Idoso , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/fisiopatologia , Doença Crônica , Corantes , Método Duplo-Cego , Feminino , Angiofluoresceinografia , Humanos , Verde de Indocianina , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Estudos Prospectivos , Ranibizumab , Retina/patologia , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Resultado do Tratamento , Verteporfina , Acuidade Visual/fisiologiaRESUMO
Given the complex nature of Alzheimer's disease (AD), a cell-based model that recapitulates the physiological properties of the target neuronal population would be extremely valuable for discovering improved drug candidates and chemical probes to uncover disease mechanisms. We established phenotypic neuronal assays for the biogenesis and synaptic action of amyloid ß peptide (Aß) based on embryonic stem cell-derived neurons (ESNs). ESNs enriched with pyramidal neurons were robust, scalable, and amenable to a small-molecule screening assay, overcoming the apparent limitations of neuronal models derived from human pluripotent cells. Small-molecule screening of clinical compounds identified four compounds capable of reducing Aß levels in ESNs derived from the Tg2576 mouse model of AD. Our approach is therefore highly suitable for phenotypic screening in AD drug discovery and has the potential to identify therapeutic candidates with improved efficacy and safety potential.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Células-Tronco Embrionárias/citologia , Neurônios/citologia , Neurônios/metabolismo , Fenótipo , Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/farmacologia , Animais , Linhagem Celular , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Sinapses/efeitos dos fármacosRESUMO
Anthricin (deoxypodophyllotoxin) is a natural product isolated from Anthriscus sylvestris (L.) Hoffm. (Apiaceae). Here, we investigated the effect of anthricin on autophagy and mammalian target of rapamycin (mTOR) signaling as anticancer actions in breast cancer cells. Many studies have supported the contention that the phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 pathway is considerably deregulated in breast cancer and that autophagy plays important roles in the development of this type of cancer, although the exact underlying mechanisms remain unknown. Our data confirmed that anthricin markedly induced apoptosis in 2 breast cancer cell lines, MCF7 (estrogen receptor positive) and MDA-MB-231 (estrogen receptor, progesterone receptor, and Her2/Neu receptor negative). Anthricin treatment decreased the levels of phosphorylated Akt and mTORC1, followed by inhibition of cell growth. Interestingly, blockage of autophagy by a pharmacological inhibitor or genetic deletion of ULK1 and Atg13 accelerated anthricin-induced apoptosis, suggesting that autophagy has cytoprotective effects. Taken together, our results indicate that anthricin is an inhibitor of mTOR and that a combination of an autophagy inhibitor and anthricin may serve as a new promising strategy for the treatment of breast cancer cells.
RESUMO
Although Alpinia officinarum has been used in traditional medicine for the treatment of several conditions, such as abdominal pain, emesis, diarrhea, impaired renal function, and dysentery, little is known about its function in obesity. In this study, we investigated the antiobesity effect of A. officinarum ethanol extract (AOE) on lipid accumulation in 3T3-L1 cells and obesity in mice fed a high-fat diet (HFD). AOE dose-dependently suppressed lipid accumulation during differentiation of 3T3-L1 preadipocytes by downregulating CCAAT enhancer binding protein α (C/EBPα), sterol regulatory element binding protein-1 (SREBP-1), and peroxisome proliferator-activated receptor-γ (PPAR-γ) genes. Galangin, a major component of A. officinarum, had antiadipogenic effects in 3T3-L1 cells. AOE supplementation in mice fed a HFD revealed that AOE significantly decreased HFD-induced increases in body, liver, and white adipose tissue weights and decreased serum insulin and leptin levels. To elucidate the inhibitory mechanism of AOE in obesity, lipid metabolism-related genes were identified. AOE efficiently suppressed protein expressions of C/EBPα, fatty acid synthase, SREBP-1, and PPAR-γ in the liver and adipose tissue. The protein expression patterns, observed by immunoblot, were confirmed by quantitative real-time polymerase chain reaction. Collectively, these results suggest that AOE prevents obesity by suppressing adipogenic and lipogenic genes. AOE has potential for use as an antiobesity therapeutic agent that can function by regulating lipid metabolism.
Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Alpinia/química , Diferenciação Celular/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Obesidade/patologia , Extratos Vegetais/farmacologia , Células 3T3-L1 , Adipócitos/citologia , Adipogenia/genética , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Sobrevivência Celular , Dieta Hiperlipídica , Regulação para Baixo , Etanol/metabolismo , Flavonoides/farmacologia , Insulina/sangue , Leptina/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , PPAR gama/genética , PPAR gama/metabolismo , RNA/genética , RNA/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Fator de Transcrição AP-2/genética , Fator de Transcrição AP-2/metabolismoRESUMO
Numerous medicinal plants and their derivatives have been reported to prevent obesity and related diseases. Although Syzygium aromaticum has traditionally been used as an anodyne, carminative and anthelmintic in Asian countries, its potential in the prevention and treatment of obesity has not yet been explored. Therefore, the present study investigated the anti-obesity effect of S. aromaticum ethanol extract (SAE) both in vitro and in vivo. To evaluate the anti-obesity potential of SAE in vitro, the effect of SAE treatment on adipocyte differentiation in 3T3-L1 cells was investigated. To evaluate its potential in vivo, mice were assigned to three groups: a group fed the American Institute of Nutrition AIN-76A diet (normal group), an experimental group fed a high-fat diet (HFD group) and an experimental group fed an HFD supplemented with 0.5% (w/w) SAE (HFD + SAE group). After 9 weeks of feeding, the body weight; white adipose tissue (WAT) mass; serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, glucose, insulin and leptin; hepatic lipid accumulation; and levels of lipid metabolism-related genes in the liver and WAT were measured. In vitro investigation of the effect of SAE treatment on 3T3-L1 cells revealed that it had efficiently inhibited the conversion of cells into adipocytes in a dose-dependent manner. In vivo investigation revealed that SAE supplementation had significantly decreased HFD-induced increases in the body weight, liver weight, WAT mass, and serum TG, TC, lipid, glucose, insulin and leptin levels. Consistent with its effects on liver weight and WAT mass, SAE supplementation was found to have suppressed the expression of lipid metabolism-related proteins, including SREBP-1, FAS, CD36 and PPARγ in the liver and WAT, in addition to downregulating mRNA levels of transcription factors including Srebp and Pparg. SAE inhibits fat accumulation in HFD-fed mice via the suppression of transcription factors integral to adipogenesis and lipogenesis, suggesting its potential in preventing obesity.
RESUMO
Pistacia chinensis has been used for various purposes in China including as an understock for grafting Pistacia vera. However, little attention was given to its health promoting effects. Therefore, in this study, we investigated the effect of Pistacia chinensis methanolic extract (PCME) containing resorcinol class of phenolic lipids on pro-inflammatory mediators and heme oxygenase-1(HO-1) in lipopolysaccharide stimulated RAW264.7 cells. While PCME (2.5-10 µg/ml) inhibited mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and interleukin (IL)-6, it up-regulated HO-1 expression. Likewise, PCME inhibited iNOS protein expression, but not COX-2, and reduced nitric oxide (NO) release. Moreover, Phosphorylated c-Jun N-terminal Kinase (JNK) was attenuated dose-dependently in PCME pre-treated RAW264.7 cells. In addition, PCME up-regulated HO-1 protein expression was diminished by pre-treatment of PI-3K inhibitor. Furthermore, nuclear factor erythroid 2 related factor 2 (Nrf2) repressor was attenuated time-dependently during PCME treatment. Taken together, our study showed (for the first time) that PCME inhibited NO production and up-regulated HO-1 induction via PI-3K/Akt pathway, suggesting the role of Pistacia chinensis as potential sources of anti-inflammatory and antioxidant natural compounds.
Assuntos
Anti-Inflamatórios/farmacologia , Heme Oxigenase-1/metabolismo , Mediadores da Inflamação/metabolismo , Inflamação , Óxido Nítrico/biossíntese , Pistacia , Extratos Vegetais/farmacologia , Animais , Antioxidantes/farmacologia , Linhagem Celular , Relação Dose-Resposta a Droga , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipídeos/farmacologia , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Fenóis/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Fitoterapia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
This study was conducted to determine the anti-obesity effects of Zanthoxylum piperitum DC fruit ethanol extract (ZPE) in 3T3-L1 adipocytes and obese mice fed a high-fat diet. We evaluated the influence of the addition of ZPE to a high-fat diet on body weight, adipose tissue weight, serum and hepatic lipids in C57BL/6 mice. In addition, adipogenic gene expression was determined by Western blot and real-time reverse transcription-PCR analysis. We assessed the effect of ZPE on 3T3-L1 preadipocyte differentiation. ZPE reduced weight gain, white adipose tissue mass, and serum triglyceride and cholesterol levels (p<0.05) in high-fat diet-fed C57BL/6 mice. ZPE decreased lipid accumulation and PPARγ, C/EBPα, SREBP-1, and FAS protein and mRNA levels in the liver. ZPE inhibited in vitro adipocyte differentiation in a dose-dependent manner and significantly attenuated adipogenic transcription factors, such as PPARγ, C/EBPα, and SREBP-1 in 3T3L1 cells. These findings suggest that Z. piperitum DC exerts an anti-obesity effect by inhibiting adipogenesis through the downregulation of genes involved in the adipogenesis pathway.
Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Extratos Vegetais/farmacologia , Zanthoxylum/química , Células 3T3 , Adipócitos/metabolismo , Adipogenia/genética , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Western Blotting , Peso Corporal/efeitos dos fármacos , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Diferenciação Celular/efeitos dos fármacos , Colesterol/sangue , Relação Dose-Resposta a Droga , Regulação para Baixo , Etanol , Frutas/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/tratamento farmacológico , PPAR gama/genética , PPAR gama/metabolismo , Polifenóis/análise , Polifenóis/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Receptor fas/genética , Receptor fas/metabolismoRESUMO
Heating and steaming processes have been applied to various natural medicines for either enhancing or altering their pharmacological activities, and the chemical compositions of the active components. While ginsenoside Rb1, which is the major constituent of raw ginseng, has been studied extensively for its anti-inflammatory effect, the biological activity of ginsenoside Rg5, a major constituent of steamed ginseng, remains to be explored. Here, we isolated Rg5 and examined anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated macrophages and on LPS-induced lung inflammation. Rg5 inhibited the expression of proinflammatory cytokines, IL-1ß and TNF-α, as well as inflammatory enzymes, COX-2 and iNOS in LPS-stimulated alveolar macrophages. Rg5 also reduced LPS-induced phosphorylation of IL-1 receptor-associated kinases (IRAK)-1 and IKK-ß, as well as the degradation of IRAK-1 and IRAK-4. Rg5 inhibited the phosphorylation of NF-κB as well as the translocation of p65 into the nucleus. When macrophages were treated with Alexa Fluor 594-conjugated LPS in the presence of Rg5, the fluorescence intensity of LPS observed outside the cell membrane was lower than that in LPS-stimulated alveolar macrophages alone. Rg5, inhibited the levels of protein and neutrophils in bronchoalveolar lavage fluid of LPS-stimulated mice, as well as pro-inflammatory cytokines, TNF-α and IL-1ß. Rg5 also inhibited iNOS and COX expressions, and NF-κB activation in LPS-stimulated lung inflammation of mice. The inhibitory effect of Rg5 (10 mg/kg) was comparable to that of dexamethasone (5 mg/kg). Based on these findings, Rg5 can ameliorate lung inflammation possibly by inhibiting the binding of LPS to toll-like receptor (TLR)-4 on macrophages.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Ginsenosídeos/uso terapêutico , Macrófagos Alveolares/efeitos dos fármacos , Receptor 4 Toll-Like/imunologia , Lesão Pulmonar Aguda/imunologia , Animais , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/imunologia , Ginsenosídeos/farmacologia , Quinase I-kappa B/imunologia , Proteínas I-kappa B/imunologia , Interleucina-1beta/imunologia , Lipopolissacarídeos , Macrófagos Alveolares/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Inibidor de NF-kappaB alfa , Óxido Nítrico/imunologia , Óxido Nítrico Sintase Tipo II/imunologia , Fator de Necrose Tumoral alfa/imunologiaRESUMO
OBJECTIVE: The prevalence of asthma is increasing, and asthma causes considerable socioeconomic burden worldwide. Few studies have been conducted to evaluate the risk factors associated with economic cost of asthma in Korea. This study evaluated asthma cost according to severity, control, and patient factors in Korean tertiary hospitals. METHODS: Direct and indirect costs were assessed in physician-diagnosed adult asthmatics recruited from eight tertiary hospitals in Korea. Official direct medical costs were derived from the analysis of 1-year expenditures related to hospital care utilization and asthma medication. Nonofficial medical costs, nonmedical direct costs, and indirect costs were investigated using a questionnaire designed specifically for the study. RESULTS: A total of 314 patients with persistent asthma were recruited. Both direct and indirect costs were significantly higher for patients with severe persistent asthma than for those with mild and moderate persistent asthma ($2214 vs. $871 and $978, p < .001; $2927 vs. $490 and $443, p < .001, respectively). Costs of asthma increased significantly in poorly controlled compared with somewhat controlled and well-controlled asthma ($7009.8 vs. $2725.3 vs. $1517.3, respectively; p < .001). After stratification for severity, a significant cost increase in the poorly controlled asthma group was observed only for indirect costs and not for direct costs. A multivariate analysis showed that female gender was a risk factor for increased indirect costs. CONCLUSION: The burden of asthma was higher both for patients with severe persistent asthma and for patients with poorly controlled asthma. More effective strategies are needed to improve control status, particularly targeting patients with severe asthma.
Assuntos
Asma/economia , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitais/classificação , Idoso , Assistência Ambulatorial/economia , Antiasmáticos/economia , Asma/diagnóstico , Asma/fisiopatologia , Asma/terapia , Terapias Complementares/economia , Feminino , Volume Expiratório Forçado/fisiologia , Hospitalização/economia , Humanos , Masculino , Medicina Tradicional do Leste Asiático/economia , Pessoa de Meia-Idade , Qualidade de Vida , República da Coreia , Fatores Sexuais , Inquéritos e QuestionáriosRESUMO
Suaeda asparagoides (Miq.) has long been used as a Korean folk herbal medicine for the treatment of functional gastrointestinal disorders. However, reports on its pharmacological activity on gastrointestinal motility are scarce. The present study investigated the effects of Suaeda asparagoides water fraction of the extract (SAWF) on antral motility in vitro. Muscle strips from rat gastric antrum were set up in an organ bath in a circular orientation. SAWF (100 µg/mL) inhibited the spontaneous contraction of antral circular muscle strips. These inhibitory effects were not significantly affected by tetrodotoxin (1 µM), N(ω)-Nitro-L-arginine methyl ester hydrochloride (100 µM), 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (10 µM), ryanodine (10 µM) and phentolamine (10 µM). SAWF-induced inhibition was mostly restored by cyclopiazonic acid (10 µM). Furthermore, the ß-adrenergic receptor antagonist, propranolol (10 µM), abolished SAWF-induced inhibition. These results suggest that SAWF may exert its activity on gastrointestinal smooth muscle via â-adrenergic receptors and sarcoplasmic reticulum Ca(2+) ATPase.
RESUMO
This study investigated the effects of dietary conjugated linoleic acid (CLA), in the form of free fatty acid (FFA-CLA) or triacylglycerol (TG-CLA), on serum and liver lipid composition and gene expression associated with lipogenesis and ß-oxidation in high-fat-diet (HFD)-induced obese C57BL/6J mice. Animals were fed a control diet, HFD, HFD supplemented with 2% FFA-CLA, or HFD supplemented with 2% TG-CLA for 8 weeks. Supplementation with both forms of CLA significantly reduced the weights of whole body and adipose tissue and was positively associated with significant liver enlargement. Both forms of CLA significantly decreased serum TG concentration, but had no effect on total cholesterol levels, which were increased in mice fed HFD. There was a prominent increase in serum alanine aminotransferase (ALT) levels in mice that received either form of CLA. TG accumulation and lipogenic gene expression, including the expression of genes for fatty acid synthase (FAS), acetyl-coenzyme A carboxylase (ACC), and malic enzyme, were significantly lower in the livers of mice that received TG-CLA as compared to FFA-CLA. The gene expressions of sterol regulatory element binding protein-1c (SREBP-1c) in both liver and adipose tissue were suppressed in mice that were fed either form of CLA as compared to the mice fed HFD alone, whereas there were no increases in the levels of expression of ß-oxidation-related genes. These findings demonstrated that free and esterified forms of CLA have differing effects on liver and adipose tissue lipogenesis.
Assuntos
Ácidos Linoleicos Conjugados/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/metabolismo , Esterificação , Humanos , Ácidos Linoleicos Conjugados/química , Lipogênese , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos ObesosRESUMO
We have previously shown a more potent impact of knockout of Cu,Zn-superoxide dismutase (SOD1) than that of Se-dependent glutathione peroxidase-1 (GPX1) on murine hepatotoxicity induced by an intraperitoneal (ip) injection of a high dose of acetaminophen (APAP, 600 mg/kg). The objective of this experiment was to compare the temporal impacts of knockouts of GPX1 and SOD1 alone or together on mouse susceptibility to an injection of a low dose of APAP (300 mg/kg). The APAP-mediated rises in plasma alanine aminotransferase activity and nitrate/nitrite concentrations, hepatic GSH depletion, and hepatic protein nitration at 5 and (or) 24 h were nearly abolished (P < 0.05) in SOD1-/- or GPX1 and SOD1 double-knockout (DKO) mice, while GPX1-/- mice exerted only moderate or no change compared with the WT. Despite an increased (P < 0.05) APAP-N-acetylcysteine and decreased APAP-glucuronide (P < 0.05) relative to the total APAP metabolites in urine collected for 24 h after the APAP injection, the SOD1-/- mice displayed no shift in urinary APAP-cysteine compared with the WT mice. Knockout of SOD1 prevented the APAP-induced hepatic GPX inactivation (P < 0.05), whereas knockout of GPX1 aggravated the APAP-induced hepatic SOD activity loss (P < 0.05). However, the APAP-mediated activity changes of these enzymes in liver accompanied no protein alterations. In conclusion, knockout of GPX1 or SOD1 exerted differential impact on mouse susceptibility to this low dose of APAP, but neither shifted urinary APAP-cysteine formation.