Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Biosci Biotechnol Biochem ; 84(1): 134-142, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31490096

RESUMO

Plumbagin (PLB), an alkaloid obtained from the roots of the plants of Plumbago genus, is an inhibitor of NADPH oxidase 4 (NOX4). This study aimed to investigate the beneficial effect of PLB against oxygen-glucose deprivation/reoxygenation (OGDR)-induced neuroinjury in human SH-SY5Y neuronal cultures. Our results showed that OGD/R stimulated NOX4 protein expression and reactive oxygen species (ROS) production in SH-SY5Y cells, whereas increased 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) production, resulting in the activation of the NLRP3 inflammasome. And PLB pretreatment reduced the ROS production by regulating the expression of NOX4 and downregulated NF-κB signaling which was induced by OGDR. Furthermore, PLB inhibited OGDR induced NLRP3 inflammasome activation but not PARP1. Overall, PLB improved OGDR induced neuroinjury by inhibiting NOX4-derived ROS-activated NLRP3 inflammasome.


Assuntos
Hipóxia Celular/efeitos dos fármacos , Glucose/deficiência , Inflamassomos/metabolismo , NADPH Oxidase 4/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Naftoquinonas/farmacologia , Neurônios/metabolismo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Isquemia Encefálica/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/química , Plumbaginaceae/química
2.
Korean J Physiol Pharmacol ; 23(1): 21-28, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30627006

RESUMO

Swertiamarin (STM) is an iridoid compound that is present in the Gentianaceae swertia genus. Here we investigated antiapoptotic effects of STM on carbon tetrachloride (CCl4)-induced liver injury and its possible mechanisms. Adult male Sprague Dawley rats were randomly divided into a control group, an STM 200 mg/kg group, a CCl4 group, a CCl4+STM 100 mg/kg group, and a CCl4+STM 200 mg/kg group. Rats in experimental groups were subcutaneously injected with 40% CCl4 twice weekly for 8 weeks. STM (100 and 200 mg/kg per day) was orally given to experimental rats by gavage for 8 consecutive weeks. Hepatocyte apoptosis was determined by TUNEL assay and the expression levels of Bcl-2, Bax, and cleaved caspase-3 proteins were evaluated by western blot analysis. The expression of TGF-ß1, collagen I, collagen III, CTGF and fibronectin mRNA were estimated by qRT-PCR. The results showed that STM significantly reduced the number of TUNEL-positive cells compared with the CCl4 group. The levels of Bax and cleaved caspase-3 proteins, and TGF-ß1, collagen I, collagen III, CTGF, and fibronectin mRNA were significantly reduced by STM compared with the CCl4 group. In addition, STM markedly abrogated the repression of Bcl-2 by CCl4. STM also attenuated the activation of the PI3K/Akt pathway in the liver. These results suggested that STM ameliorated CCl4-induced hepatocyte apoptosis in rats.

3.
Braz. J. Pharm. Sci. (Online) ; 54(4): e17449, 2018. graf
Artigo em Inglês | LILACS | ID: biblio-1001568

RESUMO

The aim of the present study is to illustrate the effects of swertiamarin (STM), a natural iridoid from herbal medicines, on hepatic inflammation induced by carbon tetrachloride (CCl4) in rats. Male Sprague Dawley rats were exposed to CCl4 with or without STM co-administration for 8 weeks. Our results revealed that STM administration (100 and 200 mg/kg b.w.) significantly attenuated inflammation in livers of CCl4-treated rats. STM remarkably reduced the production of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein-1a (MIP-1α), and monocyte chemotactic protein-1 (MCP-1) in liver tissue of CCl4-treated rats. In addition, STM treatment downregulated connective tissue growth factor (CTGF) and ser307pIRS-1 expression, which was induced by CCl4 exposure. In the process of exploring the anti-inflammatory mechanisms of STM action, we demonstrated that STM significantly inhibited Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65 expression in the liver. In conclusion, these results suggested that the inhibition of CCl4-induced inflammation by STM was, at least in part, due to its regulation of the TLR4 /NF-κB signaling pathway


Assuntos
Animais , Masculino , Ratos , Tetracloreto de Carbono/farmacologia , Receptor 4 Toll-Like , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , NF-kappa B , Gentianaceae/classificação , Glicosídeos/efeitos adversos , Inflamação/tratamento farmacológico
4.
Pak J Pharm Sci ; 30(2(Suppl.)): 573-578, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28650323

RESUMO

Plumbagin (PLB) isolated from Plumbago zeylanica L (Plumbaginaceae) was evaluated for the suppressive effect and mechanism on ADP induced rat platelet aggregation. Adult male SD rats were randomly divided into control group, clopidogrel group, PLB 25mg/kg group and PLB 50mg/kg group. Clopidogrel (13.5mg/kg per day) and PLB (25 and 50mg/kg per day) were orally given to experimental rats by gavage for seven consecutive days. The antiplatelet properties were assessed by measuring the ADP-induced platelet aggregation rate (Aggmax). The level of cAMP in platelets before aggregation was determined by ELISA. The protein expression of pAkt, Akt, pPLC ß3 and PLC ß3 in platelets was measured by western blot. Our data indicated that PLB (25 and 50mg/kg) significantly inhibited ADP-induced rat platelet aggregation as well as clopidogrel (13.5mg/kg) in a dose dependent manner compared with the control group. PLB (25 and 50mg/kg) remarkably reduced the ADP-induced PLC ß3 phosphorylation but not Akt in platelets as compared with the control group. The present study suggests that PLB exerts a suppressive effect on ADP-induced rat platelet aggregation, at least in part, through P2Y1-PLC signaling pathway.


Assuntos
Difosfato de Adenosina/farmacologia , Naftoquinonas/farmacologia , Inibidores da Agregação de Plaquetas/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Receptores Purinérgicos P2Y1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfolipases Tipo C/metabolismo , Animais , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Clopidogrel/farmacologia , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Masculino , Proteína Oncogênica v-akt/metabolismo , Fosfolipase C beta/metabolismo , Fosforilação/efeitos dos fármacos , Ratos
5.
J Ethnopharmacol ; 190: 22-32, 2016 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-27237619

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Calculus Bovis, also known as Niuhuang, is a rare traditional Chinese medicine that has been widely used in China for 2000 years in pharmacology for sedation, anti-spasm, relieving fever, diminishing inflammation and recovering gallbladder functions. AIM OF THE STUDY: This study aimed to investigate the choleretic potential and molecular responses in rats to Calculus Bovis (CB) administration after 17α-ethynylestradiol (EE)-induced cholestasis. MATERIAL AND METHODS: CB (50 and 100mg/kg per day) was intragastrically (i. g.) given to experimental rats for five consecutive days in coadministration with EE (5mg/kg daily for five days, s.c.). The levels of serum biomarkers were determined biochemically. The histopathology of the liver tissue was evaluated. Expression of bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2) were studied by western blot and immunohistochemical assay. The expression of Akt and phospho-Akt (pAkt) were also measured by western blot. RESULTS: In response to EE, CB treatment significantly prevented an increase in serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyltransferase (GGT) and total bilirubin (TBIL). CB treatment also repaired tissue lesions caused by EE. Western blots showed that EE significantly decreased the protein expression of BSEP and MRP2. EE also dramatically increased levels of pAkt and decreased levels of Akt. Compared to the EE group, CB treatment increased levels of hepatic BSEP and MRP2 while pAkt levels decreased and Akt levels increased. Immunohistochemistry also indicated that EE decreased the expression of BSEP and MRP2. LY294002 is a selective PI3K inhibitor and showed similar beneficial effects as CB. Decreased expression of BSEP and MRP2 caused by EE were also prevented by LY294002 treatment. CONCLUSION: Calculus Bovis administration can alleviate liver injury and up-regulate the expression of BSEP and MRP2 in 17α-ethynylestradiol-induced cholestasis by a mechanism that may involve inhibiting the activated PI3K/Akt signaling pathway.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Colagogos e Coleréticos/farmacologia , Colestase/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Estradiol/análogos & derivados , Fígado/diagnóstico por imagem , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Animais , Bilirrubina/sangue , Produtos Biológicos , Biomarcadores/sangue , Colestase/induzido quimicamente , Colestase/enzimologia , Colestase/patologia , Modelos Animais de Doenças , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/enzimologia , Fígado/patologia , Masculino , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
6.
Talanta ; 75(1): 104-10, 2008 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-18371854

RESUMO

Immobilized phospholipid capillary electrophoresis (IPCE) was developed for studying the interactions between a set of nonsteroidal anti-inflammatory drugs (NSAIDs) and membrane and predicting the biological activity of NSAIDs. Supported vesicle layers and supported phospholipid bilayers were attached to the inner surface of a capillary wall simply by rinsing with liposome solutions. The liposomes, composed of soybean phosphatidylcholine (SPC) or SPC and different proportions of cholesterol (Ch), were small unilamellar vesicles prepared by sonication. The normalized capacity factor (K(IPCE)) was introduced into IPCE for evaluating drug-membrane interactions. Related theories and equations were derived to calculate K(IPCE) values from apparent migration time of a solute and electroosmotic flow. The strong relationships were observed between logK(IPCE) (SPC) values and logK(lw) values (the partition coefficients determined in free SPC-liposome partitioning system) (R=0.9855 and P<0.0001) or logK(ILC) values (the normalized capacity factors determined by immobilized POPC-liposome chromatography, POPC represents 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) (R=0.9875 and P<0.0001). In addition, logK(IPCE) (SPC/Ch 80:20%) values correlated well with the pIC50 (the minus logarithm of IC50) values for cyclooxygenase 2 determined on intact cells (R=0.959 and P<0.001). These results confirmed that IPCE, K(IPCE) value as evaluation index, can be effectually used for studying drug-membrane interactions and it has the potential to predict drug activity. Cholesterol-containing (20 mol%) liposomes may be more suitable to mimic real cell membrane.


Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Membrana Celular/química , Eletroforese Capilar/métodos , Fosfolipídeos/química , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Fosfatidilcolinas/química
7.
Zhong Yao Cai ; 30(5): 558-60, 2007 May.
Artigo em Chinês | MEDLINE | ID: mdl-17727061

RESUMO

OBJECTIVE: To investigate the chemical constituents of the aerial parts of Plumbago zeylanica Linn. METHODS: The constituents of the EtOAc-soluble portion in the 95% ethanol extract were isolated and purified by means of chromatography. Compounds were identified by their physical characteristics and spectral features. RESULTS: Nine compounds were isolated as plumbagin (I), isoshinanolone (II), plumbagic acid (III), beta-sitosterol (IV), 4-hydroxybenzaldehyde (V), trans-cinnamic acid (VI), vanillic acid (VII), 2, 5-dimethyl-7-hydroxychromone (VIII), indole-3-carboxaldehyde (IX). CONCLUSION: Compounds V, VII, VIII and IX were isolated for the first time from Plumbago Linn.


Assuntos
Benzaldeídos/isolamento & purificação , Indóis/isolamento & purificação , Plantas Medicinais/química , Plumbaginaceae/química , Ácido Vanílico/isolamento & purificação , Benzaldeídos/química , Cinamatos/química , Cinamatos/isolamento & purificação , Indóis/química , Espectroscopia de Ressonância Magnética/métodos , Estrutura Molecular , Naftoquinonas/química , Naftoquinonas/isolamento & purificação , Componentes Aéreos da Planta/química , Sitosteroides/química , Sitosteroides/isolamento & purificação , Tetra-Hidronaftalenos/química , Tetra-Hidronaftalenos/isolamento & purificação , Ácido Vanílico/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA