RESUMO
PURPOSE: This non-randomized study was performed to evaluate the effects of music therapy on labor pain, the childbirth experience, and self-esteem in women during vaginal delivery. METHODS: In total, 136 primiparous women over 37 weeks of gestation receiving epidural analgesia during vaginal delivery were recruited via convenience sampling. To minimize diffusion effects, data from the control group (n=71) were collected first (April 2020 to March 2021), followed by data from the music group (n=65; April 2021 to May 2022). Participants in the music group listened to classical music during labor, while the control group was offered usual care (no music). Labor pain was measured using a numeric rating scale (NRS), and self-esteem and childbirth experience were collected using self-report questionnaires. Data were analyzed using the independent t-test, chi-square test and Cronbach's α coefficients. RESULTS: The overall pain level (NRS) at baseline was 0 in both groups. Mothers in the music therapy group had lower levels of latent pain (t=1.95, p=.005), active pain (t=3.69, p<.001) and transition-phase pain (t=7.07, p<.001) than the control group. A significant difference was observed between the two groups, and the music therapy group expressed more positive perceptions of the childbirth experience (t=-1.36, p=.018). For self-esteem, the experimental group's score was slightly higher, but without a statistically significant difference from the control group. CONCLUSION: Using music therapy during labor decreased labor pain and improved the childbirth experience. Music therapy can be clinically recommended as a non-pharmacological, safe, and easy method for nursing care in labor. Clinical trail number: KCT008561.
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The genus Artemisia is an important source of medicines in both traditional and modern pharmaceutics, particularly in East Asia. Despite the great benefits of herbal medicine, quality assessment methods for these medicinal herbs are lacking. The young leaves from Artemisia species are generally used, and most of the species have similar morphology, which often leads to adulteration and misuse. This study assembled five complete chloroplast genomes of three Artemisia species, two accessions of A. gmelinii and A. capillaris, and one A. fukudo. Through comparative analysis, we revealed genomic variations and phylogenetic relationships between these species and developed seven InDel-based barcode markers which discriminated the tested species from each other. Additionally, we analyzed specialized metabolites from the species using LC-MS and suggested chemical markers for the identification and authentication of these herbs. We expect that this integrated and complementary authentication method would aid in reducing the misuse of Artemisia species.
Assuntos
Artemisia , Genoma de Cloroplastos , Plantas Medicinais , Artemisia/genética , Filogenia , Fitoterapia , Plantas Medicinais/genéticaRESUMO
Inflammatory bowel disease (IBD) is a chronically relapsing inflammatory disorder of the gastrointestinal tract. Current IBD treatments are associated with poor tolerability and insufficient therapeutic efficacy, prompting the need for alternative therapeutic approaches. Recent advances suggest promising interventions based on a number of phytochemicals. Herein, we explored the beneficial effects of tussilagone, a major component of Tussilago farfara, in mice subjected to acute colitis induced by dextran sulfate sodium (DSS). Treatment with tussilagone resulted in a significant protective effect against DSS-induced acute colitis in mice via amelioration of weight loss, and attenuation of colonic inflammatory damage. Additionally, the expression of tumor necrosis factor-α and interleukin-6 and the activity of myeloperoxidase in colonic tissues were significantly reduced in tussilagone-treated mice. Furthermore, immunohistochemical analysis revealed that tussilagone treatment reduced the numbers of nuclear factor-kappa B (NF-κB) and increased the numbers of nuclear factor erythroid 2-related factor 2 (Nrf2) in nuclei of colonic tissues. Taken together, tussilagone treatment attenuated DSS-induced colitis in mice through inhibiting the activation of NF-κB and inducing Nrf2 pathways, indicating that tussilagone is a potent therapeutic candidate for treatment of intestinal inflammation.
Assuntos
Colite/prevenção & controle , Sesquiterpenos/uso terapêutico , Tussilago/química , Animais , Colite/induzido quimicamente , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Heme Oxigenase-1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Peroxidase/metabolismo , Sesquiterpenos/farmacologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Tussilago/metabolismoRESUMO
Syntheses of natural homoisoflavonoids, (±)-portulacanones A-C (4, 8 and 9), portulacanone D (6), isolated from Portulaca oleracea L. (POL) and their derivatives (3, 5 and 7) have been achieved for the first time along with the synthesis of known derivatives (1 and 2) and their in vitro inhibitory effect against NO production in LPS-induced RAW-264.7 macrophages was evaluated as an indicator of anti-inflammatory activity. All the compounds tested had a concentration-dependent inhibitory effect on NO production by RAW-264.7 macrophages without obvious cytotoxicity. Compounds 3 (97.2% at 10⯵M; IC50â¯=â¯1.26⯵M) followed by 6 (portulacanone D) (92.5% at 10⯵M; IC50â¯=â¯2.09⯵M), 1 (91.4% at 10⯵M; IC50â¯=â¯1.75⯵M) and 7 (83.0% at 10⯵M; IC50â¯=â¯2.91⯵M) were the most potent from the series. This finding was further correlated with the suppressed expression of iNOS induced by LPS. Our promising preliminary results may provide the basis for the assessment of compound 3 as a lead structure for a NO production-targeted anti-inflammatory drug development and also could support the usefulness of POL as a folklore medicinal plant in the treatment of inflammatory diseases.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Isoflavonas/farmacologia , Macrófagos/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Isoflavonas/síntese química , Isoflavonas/química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Células RAW 264.7 , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Pristimerin is a quinonemethide triterpenoid with anti-cancer, anti-angiogenic, anti-inflammatory and anti-protozoal activity. However, the therapeutic role of pristimerin in colitis-associated colorectal carcinogenesis is unknown. PURPOSE: We sought to examine the therapeutic effects of pristimerin on colitis-associated colon cancer induced in mice using azoxymethane (AOM)/dextran sulfate sodium (DSS). The goal was to identify the potential mechanism of action underlying the pharmacological activity of pristimerin. METHODS: BALB/c mice were injected with AOM and administered 2% DSS in drinking water. The mice were fed with a diet supplemented with pristimerin (1 to 5â¯ppm), and colonic tissue was collected at 64 days. The inflammatory status of the colon was assessed by determining the levels of cyclooxygenase-2, inducible nitric oxide synthase and pro-inflammatory cytokines using Western blotting, immunohistochemistry and real-time RT-PCR analyses. Markers of proliferation (proliferating cell nuclear antigen) and apoptosis (TUNEL) were identified in the colon tissues immunohistochemically. The levels of cell cycle-, apoptosis-, and signaling-related proteins were detected by Western blot in colon tissues. RESULTS: Administration of pristimerin significantly reduced the formation of colonic tumors. Western blot and immunohistological analyses revealed that dietary pristimerin markedly reduced NF-κB-positive cells and levels of inflammation-related proteins in colon tissue. Pristimerin also reduced cell proliferation, induced apoptosis, and decreased the phosphorylation of AKT and FOXO3a in colon tissue. CONCLUSION: Pristimerin administration decreased inflammation and proliferation induced by AOM/DSS in colon tissue. It also induced apoptosis and regulated the AKT/FOXO3a signaling pathway. Overall, this study indicates the potential value of pristimerin in suppressing colon tumorigenesis.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Colite/complicações , Neoplasias do Colo/tratamento farmacológico , Triterpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Azoximetano/toxicidade , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colite/induzido quimicamente , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Feminino , Proteína Forkhead Box O3/metabolismo , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Triterpenos Pentacíclicos , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Ziyuglycoside II, a major bioactive compound of Sanguisorba officinalis L., displays anticancer potential against several human cancer cells. However, little information concerning its antiangiogenic properties and possible mechanisms is available. The aim of this study was to investigate the inhibitory effects of ziyuglycoside II on angiogenesis. Ziyuglycoside II inhibited the proliferation, migration, and tubule formation of human umbilical vein endothelial cells, as well as the number of microvessels growing from the aortic rings. The underlying antiangiogenic mechanism of ziyuglycoside II correlated with blocking vascular endothelial growth factor receptor-2 and the fibroblast growth factor receptor-1 mediated signaling pathway. Moreover, an in vivo Matrigel plug assay in mice showed a significant decrease in vascularization and hemoglobin content in the plugs from ziyuglycoside II-treated mice compared with control mice. Overall, these results suggest that ziyuglycoside II inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects. Copyright © 2017 John Wiley & Sons, Ltd.
Assuntos
Inibidores da Angiogênese/farmacologia , Neovascularização Patológica/tratamento farmacológico , Sanguisorba/química , Saponinas/farmacologia , Animais , Aorta/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos Sprague-Dawley , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Taraxacum officinale is a distributed weedy plant used as a traditional medicinal herb belonging to the family Asteraceae. The complete chloroplast genome of T. officinale was generated by de novo assembly with whole genome sequence data. The chloroplast genome was 151 324 bp in length, which consisted of a large single copy region of 83 895 bp and a short single copy region of 18 549 bp separated by a pair of inverted repeat regions of 24 440 bp. The chloroplast genome contained 79 protein-coding genes, 29 tRNA genes and four rRNA genes. Phylogenetic analysis revealed that T. officinale was closely related to Lactuca sativa.
RESUMO
In this study, complete chloroplast sequences of Artemisia gmelinii and Artemisia capillaris (the Asteraceae family), which have been used as herbal medicine in Korea, were characterized by de novo assembly with whole-genome sequence data. The genomes of A. gmelinii and A. capillaris were 151,318 bp and 151,056 bp in length, respectively. Both genomes harbored identical number of annotated genes, such as 80 protein coding genes, 4 rRNA genes and 30 tRNA genes. Phylogenetic tree revealed that both A. gmelinii and A. capillaris were closely grouped with other Artemisia species.
RESUMO
Eclipta prostrata is an herbal medicinal plant belonging to the Asteraceae family. In this study, complete chloroplast genome sequence of the E. prostrata was characterized by de novo assembly using whole genome sequence data. The genome of E. prostrata was 151,757 bp in length, which was composed of large single copy region of 83,285 bp, small single copy region of 18,346 bp and a pair of inverted repeat regions of 25,063 bp. The genome harboured 80 protein coding sequences, 30 tRNA genes and 4 rRNA genes. We confirmed close taxonomic relationship between E. prostrata and Helianthus annuus through phylogenetic analysis with chloroplast protein-coding genes.
RESUMO
Cucurbitacin-I is a triterpenoids found in medicinal plants and have diverse pharmacological and biological activities. In this study, the antitumor effects of cucurbitacin-I on colon cancer and possible roles in apoptosis and cell cycle arrest were investigated. Treatment of SW480 cells, a human colon cancer cells, with cucurbitacin-I decreased cell viability and cell proliferation in a concentration-dependent manner. Also, cucurbitacin-I induced G2/M phase cell cycle arrest in SW480 cells with a decreased expression of cell cycle proteins including cyclin B1, cyclin A, CDK1, and CDC25C. Moreover, cucurbitacin-I induced increased cleavage of caspase-3, -7, -8, -9, and poly ADP ribose polymerase. When we examined the inhibitory effect of cucurbitacin-I on tumor growth in vivo, cucurbitacin-I effectively inhibited the tumorigenicity and growth of CT-26 cells in syngenic BALB/c mice. In summary, the present study showed that cucurbitacin-I reduced colon cancer cell proliferation by enhancing apoptosis and causing cell cycle arrest at the G2/M phase.
Assuntos
Apoptose/fisiologia , Pontos de Checagem do Ciclo Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Cucurbitaceae/química , Triterpenos/farmacologia , Animais , Western Blotting , Proteína Quinase CDC2 , Caspases/metabolismo , Linhagem Celular Tumoral , Ciclina A/análise , Ciclina A/metabolismo , Ciclina B1/análise , Ciclina B1/metabolismo , Quinases Ciclina-Dependentes/análise , Quinases Ciclina-Dependentes/metabolismo , Citometria de Fluxo , Humanos , Masculino , Potencial da Membrana Mitocondrial , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/metabolismo , Triterpenos/uso terapêutico , Fosfatases cdc25/análise , Fosfatases cdc25/metabolismoRESUMO
Water-soluble anionic macromolecules isolated from Codium fragile and fractionated using ion-exchange chromatography were investigated to determine their molecular characteristics and immunostimulating activity. The crude molecules and fractions (F1, F2, and F3) consisted mostly of carbohydrates (44.1-80.5%), sulfates (3.2-22.2%) and proteins (3.0-15.7%) with small amounts of uronic acids (1.1-4.2%), and included different levels of mannose (91.3-18.7%), glucose (62.7-8.6%) and galactose (37.5-59.5%). These molecules contained one or two subfractions with molecular weights (Mw) ranging from 148×10(3) to 4879×10(3)g/mol. The crude, F1 and F2 stimulated RAW264.7 cells to produce considerable amounts of pro-inflammatory mediator nitric oxide (NO) and cytokines. The treatment of sample molecules facilitated the degradation of Iκ-B and phosphorylation of MAPK in RAW264.7 cells, suggesting that they might stimulate RAW264.7 cells through the activation of NF-κB and MAPK pathway. Proteins in fraction F2 were essential to possess its bioactivity and its main backbone was composed of mixed linkages of (1â3)-α and ß-d-mannan.
Assuntos
Proteínas de Algas/isolamento & purificação , Clorófitas/química , Glicoproteínas/isolamento & purificação , Macrófagos/efeitos dos fármacos , Extratos Vegetais/química , Alga Marinha/química , Proteínas de Algas/química , Proteínas de Algas/farmacologia , Animais , Linhagem Celular , Cromatografia por Troca Iônica , Galactose/química , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/química , Glicoproteínas/química , Glicoproteínas/farmacologia , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Mananas/química , Manose/química , Camundongos , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Scrophularia buergeriana Miquel (Scrophulariaceae, SB) is a biennial plant native to Korea, northern China, and Japan that plays an important role in traditional medicine. The dried root of SB has long been used in oriental medicine for treatment of fever, swelling, constipation, pharyngitis, neuritis, and laryngitis. In the present study, we evaluated the ethanol extract of SB (SBE) to determine if it exerted any anti-allergic effects that had not previously been demonstrated. SBE markedly inhibited ß-hexosaminidase and histamine release and suppressed the expression of tumor necrosis factor-α and interleukin-4 cytokines by RBL-2H3 mast cells. In addition, topical treatment with SBE effectively reduced allergic inflammation in a dinitrofluorobenzene-induced contact hypersensitivity mouse model. These results strongly suggest that SBE is a promising source of anti-allergic agents.
Assuntos
Antialérgicos/farmacologia , Dermatite de Contato/tratamento farmacológico , Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Extratos Vegetais/farmacologia , Scrophularia , Animais , Degranulação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Dinitrofluorbenzeno , Orelha , Liberação de Histamina , Interleucina-4/biossíntese , Mastócitos/metabolismo , Medicina Tradicional do Leste Asiático , Camundongos , Fator de Necrose Tumoral alfa/biossíntese , beta-N-Acetil-Hexosaminidases/metabolismoRESUMO
The biological properties of ailanthoidol, a neolignan from Zanthoxylum ailanthoides or Salvia miltiorrhiza Bunge, which is used in Chinese traditional herbal medicine, have not been evaluated. Here, we report that ailanthoidol inhibits inflammatory reactions in macrophages and protects mice from endotoxin shock. Our in vitro experiments showed that ailanthoidol suppressed the generation of nitric oxide (NO) and prostaglandin E(2) , as well as the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 induced by lipopolysaccharide (LPS) in RAW264.7 cells. Similarly, ailanthoidol inhibited the production of inflammatory cytokines induced by LPS in RAW264.7 cells, including interleukin (IL)-1ß and IL-6. In an animal model, ailanthoidol protected BALB/c mice from LPS-induced endotoxin shock, possibly through inhibition of the production of inflammatory cytokines and NO. Collectively, ailanthoidol inhibited the production of inflammatory mediators and may be a potential target for treatment of various inflammatory diseases.
Assuntos
Benzofuranos/farmacologia , Inflamação/prevenção & controle , Lipopolissacarídeos/farmacologia , Choque Séptico/patologia , Animais , Linhagem Celular , Citometria de Fluxo , Inflamação/induzido quimicamente , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , NF-kappa B/metabolismoRESUMO
Although the antiangiogenic activity of indirubin-3-monoxime (I3M), a derivative of a Chinese anti-leukemia medicine, has been demonstrated using transgenic zebrafish, the detail molecular mechanism has not been elicited. To further establish its role in antiangiogenic activity, we tested its potential against human umbilical vein endothelial cells (HUVECs) and the in vivo Matrigel plug model was applied to evaluate new vessel formation. We also investigated the molecular mechanisms of I3M-induced antiangiogenic effects in HUVECs. We found that I3M significantly inhibited HUVEC proliferation (2.5-20 µM), migration (2.5-20 µM), and tube formation (10-20 µM) in HUVECs. The number of microvessels growing from the aortic rings was suppressed by I3M treatment. Moreover, I3M suppressed neovascularization in Matrigel plugs in mice. The underlying antiangiogenic mechanism of I3M was correlated with down-regulation of the vascular endothelial growth factor receptor-2 activation, at least a part. These findings emphasize the potential use of I3M in pathological situations involving stimulated angiogenesis, such as tumor development.
Assuntos
Inibidores da Angiogênese/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Indóis/farmacologia , Oximas/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/uso terapêutico , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Medicamentos de Ervas Chinesas/uso terapêutico , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Humanos , Indóis/uso terapêutico , Camundongos , Neovascularização Patológica/tratamento farmacológico , Oximas/uso terapêutico , Fosforilação , Veias Umbilicais/citologia , Veias Umbilicais/efeitos dos fármacosRESUMO
AIM OF THE STUDY: The aim of the present study was to investigate the effects of MeOH extract of PL (PLME) and its fractions on angiogenesis. MATERIALS AND METHODS: PLME and its subsequent fractions (methylene chloride, ethyl acetate, n-butanol and aqueous fractions) were evaluated in vitro. Specifically, the anti-angiogenic activities of PLME and its fractions were investigated by measuring their effects on the proliferation, migration, tube formation and phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2 in human umbilical vein endothelial cells (HUVECs). In addition, the in vivo Matrigel plug model was applied to evaluate new vessel formation. RESULTS: The results revealed that PLME and its subsequent fractions, except for the aqueous fraction, led to significant inhibition of the proliferation, migration, tube formation and VEGFR-2 phosphorylation of HUVECs as well as in vivo angiogenesis. CONCLUSIONS: These findings indicate the potential for the use of PLME in pathological situations involving stimulated angiogenesis, such as inflammation and tumor development.
Assuntos
Inibidores da Angiogênese/farmacologia , Proliferação de Células/efeitos dos fármacos , Metanol/farmacologia , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Agaricales , Inibidores da Angiogênese/isolamento & purificação , Animais , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Phellinus , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Radix Isatidis is the dried root of the plant Isatidis indigotica Fort (family Cruciferae) and traditionally used as an anti-viral, anti-bacterial, anti-endotoxic, and immune regulatory agent in the folk medicine of Korea and China. The aim of the present study was to determine the anti-inflammatory effects of methanolic extracts of Radix Isatidis (RIME) in lipopolysaccharide (LPS)-stimulated murine macrophages and in a TPA-induced ear edema animal model. Anti-inflammatory effects of RIME were examined in LPS-stimulated RAW 264.7 macrophages. In order to investigate the effects of RIME in vivo, activation of myeloperoxidase, and histological assessment were examined in the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema model. RIME significantly inhibited the release from macrophages of inflammatory mediators such as nitric oxide, prostaglandin E(2), and pro-inflammatory cytokines. Topical administration of RIME at 1-5 mg/ear resulted in reduction of ear inflammation in mice. Thus, our results indicate that the anti-inflammatory effects of RIME involve decreased production of inflammatory mediators, which suggests that RIME may have therapeutic potential in a variety of inflammation-related diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Brassicaceae , Edema/prevenção & controle , Inflamação/prevenção & controle , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Brassicaceae/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dinoprostona/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Orelha , Edema/induzido quimicamente , Edema/imunologia , Feminino , Quinase I-kappa B/metabolismo , Inflamação/induzido quimicamente , Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Metanol/química , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Peroxidase/metabolismo , Extratos Vegetais/isolamento & purificação , Raízes de Plantas , Solventes/química , Acetato de Tetradecanoilforbol , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Ebselen, an organoselenium compound that acts as a glutathione peroxidase mimetic, has been demonstrated to possess antioxidant and anti-inflammatory activities. However, the molecular mechanism underlying this effect is not fully understood in auditory cells. The purpose of the present study is to investigate the protective effect of ebselen against cisplatin-induced toxicity in HEI-OC1 auditory cells, organotypic cultures of cochlear explants from two-day postnatal rats (P(2)) and adult Balb/C mice. Pretreatment with ebselen ameliorated apoptotic death induced by cisplatin in HEI-OC1 cells and organotypic cultures of Corti's organ. Ebselen pretreatment also significantly suppressed cisplatin-induced increases in intracellular reactive oxygen species (ROS), intracellular reactive nitrogen species (RNS) and lipid peroxidation levels. Ebselen dose-dependently increased the expression level of an antioxidant response element (ARE)-luciferase reporter in HEI-OC1 cells through the translocation of Nrf2 into the nucleus. Furthermore, we found that pretreatment with ebselen significantly restored Nrf2 function, whereas it ameliorated the cytotoxicity of cisplatin in cells transfectants with either a pcDNA3.1 (control) or a DN-Nrf2 (dominant-negative) plasmid. We also observed that Nrf2 activation by ebselen increased the expression of phase II antioxidant genes, including heme oxygenase (HO-1), NAD(P)H:quinine oxidoreductase, and gamma-glutamylcysteine synthetase (gamma-GCS). Treatment with ebselen resulted in an increased expression of HO-1 and intranuclear Nrf2 in hair cells of organotypic cultured cochlea. After intraperitoneal injection with cisplatin, auditory brainstem responses (ABRs) threshold was measured on 8th day in Balb/C mice. ABR threshold shift was marked occurred in mice injected with cisplatin (16 mg/kg, n=5; Click and 8-kHz stimuli, p<0.05; 4, 16 and 32 kHz, p<0.01), whereas that of animal group which was treated with cisplatin and ebselen was not significantly changed. These results suggest that ebselen activates the Nrf2-ARE signaling pathway, which ultimately prevents free radical stresses from cisplatin and further contributes to protect auditory sensory hair cells from free radicals produced by cisplatin.
Assuntos
Azóis/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Órgão Espiral/efeitos dos fármacos , Órgão Espiral/metabolismo , Compostos Organosselênicos/farmacologia , Animais , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Transformada , Cisplatino/toxicidade , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Genes Reporter , Isoindóis , Peroxidação de Lipídeos/efeitos dos fármacos , Luciferases/genética , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/genética , Técnicas de Cultura de Órgãos , Órgão Espiral/citologia , Fenóis/metabolismo , Extratos Vegetais/genética , Extratos Vegetais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , TransfecçãoRESUMO
The aim of the present study was to investigate whether the aqueous extract of To-Sa-Za (TSZ-AE), the seed of Cuscuta chinensis Lam., which is a traditional medicinal herb commonly used in Korea and other oriental countries, could induce osteogenic activity in human osteoblast-like MG-63 cells. TSZ-AE treatment mildly promoted the proliferation of MG-63 cells at doses of 500 and 1,000 microg/mL in the 24-hour culture period. Dose-dependent increases in alkaline phosphatase (ALP) activity and collagen synthesis were shown at 48 and 72 hours of incubation. The release of bone morphogenetic protein (BMP)-2 but not osteocalcin in the MG-63 cells was induced by TSZ-AE at 72 hours (100-1,000 microg/mL). In addition, TSZ-AE markedly increased mRNA expression of ALP, collagen, and BMP-2 in the MG-63 cells in a dose-dependent manner. Mineralization in the culture of MG-63 cells was significantly induced at 500 and 1,000 microg/mL TSZ-AE treatment. In conclusion, this study shows that TSZ-AE enhanced ALP activity, collagen synthesis, BMP-2 expression, and mineralization in MG-63 cells. These results strongly suggest that C. chinensis can play an important role in osteoblastic bone formation and may possibly lead to the development of bone-forming drugs.
Assuntos
Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Cuscuta , Osteoblastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Fosfatase Alcalina/metabolismo , Proteína Morfogenética Óssea 2/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colágeno/metabolismo , Humanos , Osteoblastos/citologia , Osteocalcina/metabolismo , Extratos Vegetais/farmacologia , RNA Mensageiro/metabolismo , SementesRESUMO
The emergence of methicillin-resistant of Staphylococcus aureus (MRSA) has led to an urgent need for the discovery and development of new antibacterial agents. As part of an ongoing investigation into the antibacterial properties of the natural products, 20-Hydroxyecdysone (20E), isolated from the roots of Achyranthes japonica Nakai, was found to be active methicillin-resistant Staphylococcus aureus (MRSA), either alone or in combination with ampicillin (AM) or gentamicin (GM), vis checkerboard assay. This study investigated the antibacterial activity of 20E, which exhibited poor antibacterial activity (MIC=250-500 microg/mL) against all the bacterial strains tested. The combined activity of ampicillin (AM), gentamicin (GE) plus 20E against MRSA resulted in fractional inhibitory concentrations (FICs) ranging from 4.00 to 0.031 microg/mL, respectively. Meanwhile, the FIC index ranged from 0.16-4.50, indicating a marked synergistic relationship between AM, GE and 20E against MRSA with enterotoxin gene. Time-kill assays also showed a decrease remarkably between the combination and the more active compound. Therefore, this study demonstrated that AM, GE, and 20E can act synergistically in inhibiting MRSA in vitro.
Assuntos
Ampicilina/farmacologia , Antibacterianos/farmacologia , Ecdisterona/farmacologia , Gentamicinas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Achyranthes/química , Ampicilina/uso terapêutico , Antibacterianos/uso terapêutico , Sinergismo Farmacológico , Quimioterapia Combinada , Ecdisterona/química , Ecdisterona/uso terapêutico , Gentamicinas/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Raízes de Plantas/química , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Fatores de TempoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Inonotus obliquus (Chaga mushroom), one of the widely known medicinal mushrooms, has been used to treat various cancers in Russia and most of Baltic countries for many centuries. AIM OF THE STUDY: To examine the anti-proliferative effects of Inonotus obliquus extract on melanoma B16-F10 cells. Furthermore, to assess the anti-tumor effect of Inonotus obliquus extract in vivo in Balb/c mice. MATERIALS AND METHODS: The water extract of Inonotus obliquus was studied for anti-proliferative effects on the growth and morphology of B16-F10 melanoma cells and for anti-tumor effect using in vivo in Balb/c mice. RESULTS: Inonotus obliquus extract not only inhibited the growth of B16-F10 cells by causing cell cycle arrest at G(0)/G(1) phase and apoptosis, but also induced cell differentiation. These effects were associated with the down-regulation of pRb, p53 and p27 expression levels, and further showed that Inonotus obliquus extract resulted in a G(0)/G(1) cell cycle arrest with reduction of cyclin E/D1 and Cdk 2/4 expression levels. Furthermore, the anti-tumor effect of Inonotus obliquus extract was assessed in vivo in Balb/c mice. Intraperitoneal administration of Inonotus obliquus extract significantly inhibited the growth of tumor mass in B16-F10 cells implanted mice, resulting in a 3-fold (relative to the positive control, (*)p<0.05) inhibit at dose of 20mg/kg/day for 10 days. CONCLUSION: This study showed that the water extract of Inonotus obliquus mushroom exhibited a potential anticancer activity against B16-F10 melanoma cells in vitro and in vivo through the inhibition of proliferation and induction of differentiation and apoptosis of cancer cells.