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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 226: 117610, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31606675

RESUMO

Vaspin is a protein present in human serum that can cause type-2 diabetes, obesity, and other cardiovascular diseases. We report fluorescent upconverting nanoparticles (UCNPs)-based lateral flow biosensor for ultrasensitive detection of Vaspin. A pair (primary and secondary) of cognate aptamers was used that has duo binding with Vaspin. UCNPs with a diameter of around 100 nm were used as a tag to label a detection probe (secondary aptamer). A primary aptamer (capture probe) was immobilized on the test zone. Sandwich type hybridization reactions among the conjugate probe, target Vaspin, and primary aptamer were performed on the lateral flow biosensor. In the presence of target Vaspin, UCNPs were captured on the test zone of the biosensor and the fluorescent intensity of the captured UCNPs was measured through a colorimetric app under NIR. Fluorescence intensity indicates the quantity of Vaspin present in the sample. A range of Vaspin concentration across 0.1-55 ng ml-1 with a Limit of detection (LOD) 39 pg ml-1 was tested through this UCNPs based LFSA with high sensitivity, reproducibility and repeatability, whereas it's actual range in human blood is from 0.1 to 7 ng ml-1. Therefore, this research provides a well-suited lateral flow strip with an ultrasensitive and low-cost approach for the early diagnosis of type-2 diabetes and this could be applied to any targets with a duo of aptamers generated.

2.
Biol Pharm Bull ; 42(1): 1-9, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30381617

RESUMO

Veratrum maackii (VM), a perennial plant in the Melanthiaceae family, has anti-hypertensive, anti-cholinergic, anti-asthmatic, anti-tussive, anti-fungal, anti-melanogenesis, and anti-tumor activities. Here, we investigated the therapeutic effect of VM on benign prostatic hyperplasia (BPH) in human normal prostate cell line (WPMY-1) and a testosterone propionate-induced BPH animal model. WPMY-1 cells were treated with VM (1-10 µg/mL) and testosterone propionate (100 nM). BPH in rats was generated via daily subcutaneous injections of testosterone propionate (3 mg/kg) dissolved in corn oil, for 4 weeks. VM (150 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the testosterone propionate. All rats were sacrificed and the prostates were dissected, weighed, and subjected to histological, immunohistochemical, and biochemical examinations. Immunoblotting experiments indicated that WPMY-1 cells treated testosterone propionate had increased expression of prostate specific antigen (PSA) and androgen receptor (AR), and treatment with VM or finasteride blocked this effect. In rat model, VM significantly reduced prostate weight, prostatic hyperplasia, prostatic levels of dihydrotestosterone (DHT), and expression of proliferation markers such as proliferating cell nuclear antigen (PCNA) and cyclin D1, but increased the expression of pro-apoptotic Bcl-2-associated X protein (Bax) and the cleavage of caspase-3. VM administration also suppressed the testosterone propionate-induced activation of nuclear factor-kappaB (NF-κB). Our results indicate that VM effectively represses the development of testosterone propionate-induced BPH, suggesting it may be a useful treatment agent for BPH.


Assuntos
Extratos Vegetais/uso terapêutico , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/tratamento farmacológico , Propionato de Testosterona/toxicidade , Veratrum , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Hiperplasia Prostática/patologia , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento
3.
Mater Sci Eng C Mater Biol Appl ; 92: 477-488, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30184773

RESUMO

Most cancer patients die as a consequence of distant metastases, which are frequently unresponsive to cancer therapy. This study focuses on the anti-tumorigenic and anti-metastatic properties of tangeretin-zinc oxide quantum dots (Tan-ZnO QDs) against the NCI-H358 cell line. Tan-ZnO QDs are pH-sensitive and capitalize on the acidic pH maintained in the tumor microenvironment; therefore, targeted drug delivery is directed specifically to cancer cells, leaving the normal cells less affected. Tan was loaded into synthesized ZnO QDs, and drug loading was analyzed using Fourier transform infrared (FTIR) spectroscopy and ultraviolet-visible (UV-Vis) spectrometry. Crystalline phase and particle size were measured using transmission electron microscopy (TEM) and X-ray diffraction (XRD). Drug release was evaluated in buffered solutions with differing pH for up to 15 h. The results confirmed stable drug release (80%) in an acidic pH. Tan-ZnO QDs induced significant cytotoxicity in NCI-H358 metastatic cells, while not markedly affecting HK-2 human normal cells. Morphology of treated H358 cells analyzed via atomic force microscopy (AFM) showed an increased surface roughness and pores. Further, the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells increased after treatment with Tan-ZnO QDs. DNA fragmentation was also induced after treatment with increasing concentrations of Tan-ZnO QDs in H358 cells. We also confirmed regulation of apoptosis via expression levels of Bax and Bcl-2 proteins; G2/M phase cell cycle arrest was observed. Additionally, cell proliferation and migration drastically decreased, and cell invasion and migration, hallmarks of metastasis, were significantly inhibited in H358 cells. Matrix metalloproteinase (MMP)2 and MMP9, markers of metastasis, as well as vascular endothelial growth factor (VEGF), a marker of angiogenesis, were significantly downregulated upon treatment with Tan-ZnO QDs. In conclusion, our novel formulation destabilized H358 cells by using its acidic tumor microenvironment, thereby regulating cell apoptosis, proliferation, and metastatic properties.


Assuntos
Apoptose/efeitos dos fármacos , Flavonas , Neoplasias Pulmonares/tratamento farmacológico , Pontos Quânticos , Óxido de Zinco , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Flavonas/química , Flavonas/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metástase Neoplásica , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Óxido de Zinco/química , Óxido de Zinco/farmacologia
4.
Mater Sci Eng C Mater Biol Appl ; 81: 551-560, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28888009

RESUMO

Current trends in therapeutic research are the application of nanomaterial carriers for cancer therapy. One such molecule, ZnO, originally used in diagnosis and as a drug carrier, is gaining importance for its biological properties. Here, we report for the first time, the scope of ZnO QDs for enhanced cytotoxicity against MCF-7 and metastatic MDA-MB-231 human breast cancer cells. Unlike other ZnO nanostructures, ZnO QDs are dispersed and small sized (8-10nm) which is believed to greatly increase the cellular uptake. Furthermore, the acidic tumor microenvironment attracts ZnO QDs enhancing targeted therapy while leaving normal cells less affected. Results from MTT assay demonstrated that ZnO QDs induced cytotoxicity to MCF-7 and metastatic MDA-MB-231 breast cancer cells at very low concentrations (10 and 15µg/ml) as compared to other reported ZnO nanostructures. HEK-293 cells showed less toxicity at these concentrations. Confocal microscope images from DAPI staining and TUNEL assay demonstrated that ZnO QDs induced nuclear fragmentation and apoptosis in MCF-7 and MDA-MB-231. FACS results suggested ZnO QDs treatment induced cell cycle arrest at the G0/G1 phase in these cells. ZnO QDs drastically decreased the proliferation and migration of MCF-7 and MDA-MB-231 as seen from the results of the clonogenic and wound healing assays respectively. Furthermore, our data suggested that ZnO QDs regulated apoptosis via Bax and Bcl-2 proteins as validated by immunofluorescence and western blot. Taken together, our findings demonstrate that these ultra-small sized ZnO QDs destabilize cancer cells by using its acidic tumor microenvironment thereby inducing apoptosis and controlling the cell proliferation and migration at low dosages.


Assuntos
Neoplasias da Mama , Pontos Quânticos , Antineoplásicos , Apoptose , Linhagem Celular Tumoral , Humanos , Óxido de Zinco
5.
Biol Pharm Bull ; 40(12): 2125-2133, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28943529

RESUMO

Quisqualis indica (QI) has been used for treating disorders such as stomach pain, constipation, and digestion problem. This study was aimed to evaluate the therapeutic efficacy of QI extract on treating benign prostatic hyperplasia (BPH) in LNCaP human prostate cancer cell line and a testosterone-induced BPH rat model. LNCaP cells were treated with QI plus testosterone propionate (TP), and androgen receptor (AR) and prostate specific antigen (PSA) expression levels were assessed by Western blotting. To induce BPH, the rats were subjected to a daily subcutaneous injection of TP (3 mg/kg) for 4 weeks. The rats in treatment group were orally gavaged with QI (150 mg/kg) together with the TP injection. In-vitro studies showed that TP-induced increases in AR and PSA expression in LNCaP cells were reduced by QI treatment. In BPH-model rats, the prostate weight, testosterone in serum, dihydrotestosterone (DHT) concentration and 5α-reductase type 2 mRNA expression in prostate tissue were significantly reduced following the treatment with QI. TP-induced prostatic hyperplasia and the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 were significantly attenuated in QI-treated rats. In addition, QI induced apoptosis by up-regulating caspase-3 and -9 activity and decreasing the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio in prostate tissues of BPH rats. Further investigation showed that TP-induced activation of AKT and glycogen synthase kinase 3ß (GSK3ß) was reduced by QI administration. Therefore, our findings suggest that QI attenuates the BPH state in rats through anti-proliferative and pro-apoptotic activities and might be useful in the clinical treatment of BPH.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Combretaceae/química , Extratos Vegetais/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Animais , Di-Hidrotestosterona/sangue , Humanos , Masculino , Extratos Vegetais/uso terapêutico , Antígeno Nuclear de Célula em Proliferação , Próstata/citologia , Próstata/patologia , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/metabolismo , Sementes/química , Testosterona/sangue , Testosterona/metabolismo , Propionato de Testosterona/toxicidade
6.
Sci Rep ; 6: 36195, 2016 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-27811977

RESUMO

Owing to the increasing interest in the nonvolatile memory devices, resistive switching based on hybrid nanocomposite of a 2D material, molybdenum disulphide (MoS2) and polyvinyl alcohol (PVA) is explored in this work. As a proof of concept, we have demonstrated the fabrication of a memory device with the configuration of PET/Ag/MoS2-PVA/Ag via an all printed, hybrid, and state of the art fabrication approach. Bottom Ag electrodes, active layer of hybrid MoS2-PVA nanocomposite and top Ag electrode are deposited by reverse offset, electrohydrodynamic (EHD) atomization and electrohydrodynamic (EHD) patterning respectively. The fabricated device displayed characteristic bistable, nonvolatile and rewritable resistive switching behavior at a low operating voltage. A decent off/on ratio, high retention time, and large endurance of 1.28 × 102, 105 sec and 1000 voltage sweeps were recorded respectively. Double logarithmic curve satisfy the trap controlled space charge limited current (TCSCLC) model in high resistance state (HRS) and ohmic model in low resistance state (LRS). Bendability test at various bending diameters (50-2 mm) for 1500 cycles was carried out to show the mechanical robustness of fabricated device.

7.
Nat Prod Res ; 30(6): 705-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25942587

RESUMO

Allergic contact dermatitis (ACD) is a prototypic T-cell-mediated cutaneous inflammatory response. In the present study we describe the anti-allergic effect of topically applied Scutellaria bacalensis aqueous extract (WSBE) in suppressing 2,4-dinitrochlorobenzene (DNCB)-induced ACD in BALB/c mice. Topically applied WSBE attenuated the epidermal thickness and mast cell infiltration into the skin in DNCB-induced contact dermatitis. Furthermore, WSBE suppressed DNCB-induced production of serum IgE as well as IL-4, IFN-γ, and TNF-α in the skin. Topical application of WSBE also ameliorated the significant decrease in dermal glutathione and superoxide dismutase levels. Moreover, present results demonstrated that the baicalin, bioactive compound of WSBE, was able to penetrate into the skin following topical application, which was confirmed by the HPLC analysis using rat model. Taken together, topical application of WSBE exerts beneficial effects in contact dermatitis model, suggesting that WSBE might be a candidate for the treatment of contact dermatitis.


Assuntos
Antialérgicos/farmacologia , Dermatite de Contato/tratamento farmacológico , Extratos Vegetais/farmacologia , Scutellaria baicalensis/química , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Dinitroclorobenzeno , Feminino , Flavonoides/farmacologia , Imunoglobulina E/sangue , Interferon gama/metabolismo , Interleucina-4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
8.
Toxicol Appl Pharmacol ; 291: 38-45, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26701066

RESUMO

Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels of malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [(14)C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Obesidade/genética , Tioacetamida/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Dose Letal Mediana , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Tioacetamida/metabolismo
9.
Phytother Res ; 29(10): 1577-84, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26178909

RESUMO

Nobiletin and tangeretin are polymethoxy flavonoids (PMFs), found in rich quantities in the peel of citrus fruits. In the present study, we assessed the biological effect of the PMFs on liver damage using a mouse model of binge drinking. First, we extracted PMFs from the peels of Citrus aurantium to make Citrus aurantium extract (CAE). Male C57BL/6 mice were orally treated with silymarin and CAE (50, 100, and 200 mg/kg) for 3 days prior to ethanol (5 g/kg, total of 3 doses) oral gavage. Liver injury was observed in the ethanol alone group, as evidenced by increases in serum hepatic enzymes and histopathologic alteration, as well as by hepatic oxidative status disruption. CAE improved serum marker and hepatic structure and restored oxidative status by enhancing antioxidant enzyme levels and by reducing lipid peroxidation levels. In addition, CAE evidently suppressed inflammation and apoptosis in the livers of mice administered with ethanol, by 85% (tumor necrosis factor-α) and 44% compared to the control group, respectively. Furthermore, CAE activated lipid metabolism related signals and enhanced phosphorylation of AMP-activated protein kinase (AMPK) and nuclear factor E2-related factor 2 (Nrf2) with several cytoprotective proteins including heme oxygenase-1, NAD(P)H quinone oxidoreductase 1, and γ-glutamylcysteine synthetase. Taken together, the present study demonstrated that, CAE possesses antioxidant, anti-inflammatory, and antiapoptotic activity against ethanol-induced liver injury.


Assuntos
Proteínas Quinases Ativadas por AMP , Citrus , Extratos Vegetais , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Bebedeira , Citrus/química , Modelos Animais de Doenças , Etanol/farmacologia , Flavonas , Flavonoides/farmacologia , Heme Oxigenase-1/metabolismo , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Silimarina/farmacologia , Fator de Necrose Tumoral alfa
10.
Vet Microbiol ; 168(1): 131-40, 2014 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-24210811

RESUMO

The pathogenic mechanisms of Brucellosis used to adapt to the harsh intracellular environment of the host cell are not fully understood. The present study investigated the in vitro and in vivo characteristics of B. abortus betaine aldehyde dehydrogenase (BetB) (Gene Bank ID: 006932) using a betB deletion mutant constructed from virulent B. abortus 544. In test under stress conditions, including osmotic- and acid stress-resistance, the betB mutant had a lower osmotic-resistance than B. abortus wild-type. In addition, the betB mutant showed higher internalization rates compared to the wild-type strain; however, it also displayed replication failures in HeLa cells and RAW 264.7 macrophages. During internalization, compared to the wild-type strain, the betB mutant was more adherent to the host surface and showed enhanced phosphorylation of protein kinases, two processes that promote phagocytic activity, in host cells. During intracellular trafficking, colocalization of B. abortus-containing phagosomes with LAMP-1 was elevated in betB mutant-infected cells compared to the wild-type cells. In mice, the betB mutant was predominantly cleared from spleens compared to the wild-type strain after 2 weeks post-infection, and the vaccination test with the live betB mutant showed effective protection against challenge infection with the virulent wild-type strain. These findings suggested that the B. abortus betB gene substantially affects the phagocytic pathway in human phagocytes and in host cells in mice. Furthermore, this study highlights the potential use of the B. abortus betB mutant as a live vaccine for the control of brucellosis.


Assuntos
Betaína-Aldeído Desidrogenase/genética , Betaína-Aldeído Desidrogenase/metabolismo , Brucella abortus/enzimologia , Brucella abortus/patogenicidade , Brucelose/microbiologia , Fatores de Virulência/genética , Animais , Aderência Bacteriana/genética , Vacinas Bacterianas , Brucella abortus/genética , Brucella abortus/imunologia , Brucelose/imunologia , Brucelose/prevenção & controle , Células HeLa , Humanos , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Pressão Osmótica , Fagócitos/microbiologia , Deleção de Sequência , Baço/microbiologia
11.
Planta Med ; 79(11): 959-62, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23818268

RESUMO

Scutellaria baicalensis has been used as a traditional herbal medicine for bronchitis, hepatitis, and allergic diseases. The root of Scutellaria baicalensis contains active flavonoid components, including baicalin, baicalein, wogonoside, and wogonin, which have pharmaceutical properties. In the present study, the antiallergic properties of a standardized aqueous extract of S. baicalensis were evaluated, and the skin toxicity of its dermal application was also determined. The in vivo and in vitro assays were performed by using the ß-hexosaminidase assay in rat basophilic leukemia cells (RBL-2H3) and cutaneous skin reaction in BALB/c mice, respectively. In addition, the acute dermal irritation/corrosion test was carried out in New Zealand white rabbits, and the skin sensitization test was conducted by Buhler's method in Hartley guinea pigs to estimate the safety of the standardized aqueous extract of S. baicalensis for topical application. ß-Hexosaminidase release in RBL-2H3 was markedly decreased following treatment with the standardized aqueous extract of S. baicalensis. It also ameliorated antigen-induced ear swelling compared with the control group in BALB/c mice. In the toxicological studies, it did not induce any dermal irritation/corrosion in rabbits or skin sensitization in guinea pigs. Although still limited, these results concerning the toxicological effects of S. baicalensis could be an initial step toward the topical application of S. baicalensis extracts on hypersensitive skin.


Assuntos
Antialérgicos/farmacologia , Flavonoides/farmacologia , Hipersensibilidade , Extratos Vegetais/farmacologia , Administração Tópica , Animais , Antialérgicos/química , Antialérgicos/isolamento & purificação , Linhagem Celular Tumoral , Flavanonas/química , Flavanonas/isolamento & purificação , Flavanonas/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Glucosídeos/química , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Cobaias , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Plantas Medicinais , Coelhos , Ratos , Scutellaria baicalensis/química , Pele/efeitos dos fármacos , beta-N-Acetil-Hexosaminidases/análise
12.
J Plant Res ; 126(5): 661-74, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23632811

RESUMO

The warm temperate deciduous forests in Asia have a relatively dense understory, hence, it is imperative that we understand the dynamics of transpiration in both the overstory (E O) and understory (E U) of forest stands under the influence of the Asian monsoon in order to improve the accuracy of forest water use budgeting and to identify key factors controlling forest water use under climate change. In this study, E O and E U of a temperate deciduous forest stand located in South Korea were measured during the growing season of 2008 using sap flow methods. The objectives of this study were (1) to quantify the total transpiration of the forest stand, i.e., overstory and understory, (2) to determine their relative contribution to ecosystem evapotranspiration (E eco), and (3) to identify factors controlling the transpiration of each layer. E O and E U were 174 and 22 mm, respectively. Total transpiration accounted for 55 % of the total E eco, revealing the importance of unaccounted contributions to E eco (i.e., soil evaporation and wet canopy evaporation). During the monsoon period, there was a strong reduction in the total transpiration, likely because of reductions in photosynthetic active radiation, vapor pressure deficit and plant area index. The ratio of E U to E O declined during the same period, indicating an effect of monsoon on the partitioning of E eco in its two components. The seasonal pattern of E O was synchronized with the overstory canopy development, which equally had a strong regulatory influence on E U.


Assuntos
Transpiração Vegetal/fisiologia , Árvores/fisiologia , Água/fisiologia , Biometria , Meio Ambiente , Folhas de Planta/fisiologia , Caules de Planta , República da Coreia , Estações do Ano
13.
Artigo em Inglês | MEDLINE | ID: mdl-24489585

RESUMO

Hepatitis C virus (HCV) infection is a major cause of liver disease, including cirrhosis and hepatocellular carcinoma. Due to significant adverse effects and emergence of resistant strains of currently developed anti-HCV agents, plant extracts have been considered to be potential sources of new bioactive compounds against HCV. The aim of this study was to evaluate the functional effects of triterpenoid saponins contained in the root extract of Platycodon grandiflorum (PG) on viral enzyme activities and replication in both HCV replicon cells and cell culture grown HCV- (HCVcc-) infected cells. Inhibitory activities of triterpenoid saponins from PG were verified by NS5B RNA-dependent RNA polymerase assay and were further confirmed in the context of HCV replication. Six triterpenoid saponins (platycodin D, platycodin D2, platycodin D3, deapioplatycodin D, deapioplatycodin D2, and platyconic acid A), PG saponin mixture (PGSM), were identified as active components exerting anti-HCV activity. Importantly, PGSM exerted synergistic anti-HCV activity in combination with either interferon- α or NS5A inhibitors. We demonstrated that combinatorial treatment of PGSM and IFN- α efficiently suppressed colony formation with significant reduction in drug resistant variant of HCV. These data suggest that triterpenoid saponin may represent a novel anti-HCV therapeutic agent.

14.
Food Chem Toxicol ; 51: 364-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23116642

RESUMO

Platycodin D (PD) is the major triterpene saponin in the root of Platycodon grandiflorum. The aim of the present study was to evaluate the protective effects of PD on bile duct ligation (BDL)-induced cholestasis in mice. Mice were allocated to five groups: sham, BDL alone, and BDL with PD treatment at 1, 2, and 4mg/kg. PD was administered to the mice for 28 consecutive days after the BDL operation. PD treatment of BDL-operated mice decreased serum alanine aminotransferase, serum aspartate aminotransferase, and total bilirubin levels by up to 37%, 31%, and 41%, respectively, in comparison with the levels in mice that underwent BDL alone. PD treatment attenuated oxidative stress, as evidenced by an increase in anti-oxidative enzyme levels glutathione and superoxide dismutase together with a decrease in lipid peroxidation and oxidative stress indices levels of malondialdehyde and nitric oxide. Histopathological studies further confirmed the protective effects of PD on cholestasis-induced hepatic injury and liver fibrosis in mice. In addition, nuclear factor-kappa B and inducible nitric oxide synthase levels significantly decreased after PD treatment, as did the levels of hepatocyte apoptosis. Taken together, these results suggest that PD treatment might be beneficial in cholestasis-induced hepatotoxicity.


Assuntos
Colestase/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/patologia , Saponinas/farmacologia , Triterpenos/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Ductos Biliares/cirurgia , Bilirrubina/sangue , Colestase/patologia , Colestase/cirurgia , Modelos Animais de Doenças , Fibrose/tratamento farmacológico , Glutationa/sangue , Ligadura , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Superóxido Dismutase/metabolismo
15.
J Vet Med Sci ; 75(1): 89-92, 2013 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-22878539

RESUMO

The aim of the present study was to investigate the influence of different injection sites, i.e., the neck area and thigh muscle, on the pharmacokinetics of cefquinome in piglets following intramuscular (i.m.) injection. Cross-bred (Landrace × Duroc × Yorkshire) piglets were administered the same dose of cefquinome (2 mg/kg body weight) via intravenous injection and intramuscular injection into the neck area or thigh. The mean maximum concentrations (C(max)) of cefquinome following i.m. injection into neck or thigh area were 4.62 ± 0.31 µg/ml at 0.38 ± 0.14 hr and 4.39 ± 0.53 µg/ml at 0.42 ± 0.13 hr, respectively. The absolute bioavailabilities (F) of cefquinome after i.m. injection into the neck or thigh area were 103.04 ± 13.01 and 97.56 ± 16.14%, respectively (P>0.05). There were no differences noted between the two different injection sites for the pharmacokinetic properties of cefquinome after i.m. injection in piglets. Further studies will be needed to determine the incidence or severity of injection site reactions following repeated administrations of cefquinome into both injection sites.


Assuntos
Cefalosporinas/farmacocinética , Injeções Intramusculares/métodos , Injeções Intramusculares/veterinária , Sus scrofa/metabolismo , Análise de Variância , Animais , Disponibilidade Biológica , Cefalosporinas/administração & dosagem , Cromatografia Líquida/veterinária , Estudos Cross-Over , Cruzamentos Genéticos , Espectrometria de Massas/veterinária , Pescoço , Coxa da Perna
16.
Pharm Biol ; 50(12): 1473-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23035893

RESUMO

CONTEXT: The root of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae) has been widely studied for its hepatoprotective effects against various hepatotoxicants. OBJECTIVE: The present study evaluated the protective effect of the standardized aqueous extract of P. grandiflorum (BC703) on cholestasis-induced hepatic injury in mice. MATERIALS AND METHODS: BC703 is a standardized aqueous extract of P. grandiflorum in reference to platycodin D (at least 0.8%). The mice were allocated into five groups as follows: Sham-operated, bile duct ligation (BDL) alone, and BDL with BC703 (1, 5, and 10 mg/kg BW) treated group. BC703 was given for 3 consecutive days before BDL operation. The animals were sacrificed by CO2 anesthesia post-24 h of BDL operations. RESULTS AND DISCUSSION: Serum alanine aminotransferase and serum aspartate aminotransferase increased to 395.2 ± 90.0 and 266.0 ± 45.6 Unit/L in the BDL alone group and decreased with BC703 in a dose-dependent manner. Especially the 10 mg/kg of BC703-treated mice showed a 77% decrease of serum alanine aminotransferase and 56% of aspartate aminotransferase as compared with BDL alone. Decreased antioxidant enzyme levels in BDL alone group were elevated in BC703-treated groups ranging from 7 to 29% for glutathione and from 13 to 25% for superoxide dismutase. BC703 treatment also attenuated malondialdehyde (from 3 to 32%) and nitric oxide levels (from 32 to 50%) as compared with BDL alone. Histopathological studies further confirmed the hepatoprotective effect of BC703 in BDL-induced cholestesis. CONCLUSION: BC703 could attenuate liver injury by BDL in mice, and test results indicate that BC703 might be useful in cholestatic liver injury.


Assuntos
Colestase Extra-Hepática/tratamento farmacológico , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Platycodon , Substâncias Protetoras/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Colestase Extra-Hepática/sangue , Colestase Extra-Hepática/etiologia , Colestase Extra-Hepática/patologia , Cromatografia Líquida de Alta Pressão , Ducto Colédoco/cirurgia , Citoproteção , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Ligadura , Fígado/enzimologia , Fígado/patologia , Hepatopatias/sangue , Hepatopatias/etiologia , Hepatopatias/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/isolamento & purificação , Raízes de Plantas , Plantas Medicinais , Platycodon/química , Substâncias Protetoras/análise , Substâncias Protetoras/isolamento & purificação , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo
17.
J Nutr Sci Vitaminol (Tokyo) ; 58(3): 187-94, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22878389

RESUMO

The present study aims to evaluate the anti-HCV activity of hotwater extract from Platycodon grandiflorum (BC703) with HCV genotype 1b subgenomic replicon system and investigate its hepatoprotective activity on carbon tetrachloride (CCl(4))-induced acute liver damage in mice. BC703 produced significant hepatoprotective effects against CCl(4)-induced acute hepatic injury by decreasing the activities of serum enzymes, nitric oxide and lipid peroxidation. Histopathological studies further substantiated the protective effect of BC703. Furthermore, BC703 inhibited the HCV RNA replication with an EC(50) value and selective index (CC(50)/EC(50)) of 2.82 µg/mL and above 35.46, respectively. However, digested BC703 using a simulated gastric juice showed poor protective effect against CCl(4)-induced hepatotoxicity in mice and decreased anti-HCV activity as compared to the intact BC703. Although further studies are necessary, BC703 may be a beneficial agent for the management of acute hepatic injury and chronic HCV infection.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Hepacivirus/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Platycodon/química , Animais , Hepatite C/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fitoterapia , Extratos Vegetais/química
18.
Food Chem Toxicol ; 50(12): 4254-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22617354

RESUMO

Platycodin D (PD) is well known as a potent triterpenoid saponin having various pharmacological activities isolated from the root of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae). We aimed to evaluate protective effect of PD on cisplatin (CDDP)-induced nephrotoxicity. Male ICR mice were allocated into five groups as follows: Negative control, CDDP alone and CDDP with PD (0.1, 1 and 5 mg/kg) treated group. PD was given for three consecutive days before CDDP injection. Increased blood urea nitrogen (BUN) and creatinine (CRE) levels in CDDP alone treated mice were decreased to normal range by pretreatment with PD. It also decreased nitric oxide (NO) and lipid peroxidation with increased antioxidant enzymes such as glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in PD pretreated mice. In histopathological examination, pretreatment with PD showed ameliorated renal injury such as intraluminal cast formation and epithelial desquamation. Furthermore, over-expression of nuclear factor-kappa B p65 and apoptotic cells were suppressed by PD pretreatment. Taken together, PD pretreatment might be beneficial to CDDP-induced nephrotoxicity.


Assuntos
Cisplatino/toxicidade , Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , Platycodon/química , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/metabolismo , Rim/patologia , Nefropatias/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B , Óxido Nítrico/sangue , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/química , Superóxido Dismutase/metabolismo
19.
Exp Anim ; 61(1): 71-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22293675

RESUMO

This study was conducted to evaluate the oral absorption of enrofloxacin (ENFX) in rats when administered with orange oil or its main component, limonene. Compared with the group administered ENFX alone, the ENFX + limonene group did not show any significant difference in the absorption of ENFX, whereas the extent and rate of absorption of ENFX were significantly decreased in the ENFX + orange oil group (C(max), -43%; T(max), 129%). In addition, t(1/2λz) and MRT of ENFX were prolonged by the concomitant administration of orange oil. The AUCs of ENFX were not affected in the ENFX + orange oil group. These results suggest that decreased oral absorption could reduce the efficacy of ENFX therapy in animals.


Assuntos
Antibacterianos/farmacocinética , Cicloexenos/farmacocinética , Fluoroquinolonas/farmacocinética , Óleos Vegetais/farmacocinética , Terpenos/farmacocinética , Absorção/efeitos dos fármacos , Administração Oral , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Cicloexenos/administração & dosagem , Cicloexenos/sangue , Combinação de Medicamentos , Interações Medicamentosas , Enrofloxacina , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/sangue , Limoneno , Masculino , Óleos Vegetais/administração & dosagem , Ratos , Ratos Sprague-Dawley , Terpenos/administração & dosagem , Terpenos/sangue
20.
Toxicol Res ; 28(4): 263-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24278619

RESUMO

The aim of this study was to investigate the acute oral toxicity of fermented Scutellariae Radix (JKTMHGu- 100) in rats and dogs. JKTM-HGu-100 was orally administered at a dose of 2,000 mg/kg in Sprague-Dawley rats. An escalating single-dose oral toxicity test in beagle dogs was performed at doses of 500, 1000, and 2000 mg/kg with 4-day intervals. Clinical signs, changes in body weight, mortality, and necropsy findings were examined for 2 weeks following oral administration. No toxicological changes related to the test substance nor mortality was observed after administration of a single oral dose of JKTM-HGu-100 in rats or dogs. Therefore, the approximate lethal dose (LD) for oral administration of JKTMHGu-100 in rats was considered to be over 2,000 mg/kg, and the maximum tolerance doses (MTDs) in rats and dogs were also estimated to be over 2,000 mg/kg. These results indicate that JKTM-HGu-100 shows no toxicity in rodents or non-rodents at doses of 2,000 mg/kg or less.

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