RESUMO
Radix Aconiti Lateralis Preparata (fuzi) is the processed product of Aconitum carmichaelii Debeaux tuber, and has great potential anti-myocardial infarction effects, including improving myocardial damage and energy metabolism in rats. However, the effects of Radix Aconiti Lateralis Preparata extracts in a rat model of myocardial infarction have not yet been fully illustrated. Herein, Radix Aconiti Lateral Preparata was used to prepare Radix Aconiti Lateralis Preparata extract (RAE), fuzi polysaccharides (FPS), and fuzi total alkaloid (FTA). Then, we aimed to compare the effects of RAE, FPS, and FTA in MI rats and further explore their influence on small molecules in the heart. We reported that Radix Aconiti Lateralis Preparata extract (RAE) and fuzi total alkaloid (FTA) significantly improved left ventricular function and structure, and reduced myocardial damage and infarct size in rats with myocardial infarction by the left anterior descending artery ligation. In contrast, fuzi polysaccharides (FPS) was less effective than RAE and FTA, indicating that alkaloids might play a major role in the treatment of myocardial infarction. Moreover, via matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI), we further showed that RAE and FTA containing alkaloids as the main common components regulated myocardial energy metabolism-related molecules and phospholipids levels and distribution patterns against myocardial infarction. In particular, it was FTA, not RAE, that could also regulate potassium ions and glutamine to play a cardioprotective role in myocardial infarction, which revealed that an appropriate dose of alkaloids generated more obvious cardiotonic effects. These findings together suggested that Radix Aconiti Lateralis Preparata extracts containing an appropriate dose of alkaloids as its main pharmacological active components exerted protective effects against myocardial infarction by improving myocardial energy metabolism abnormalities and changing phospholipids levels and distribution patterns to stabilize the cardiomyocyte membrane structure. Thus, RAE and FTA extracted from Radix Aconiti Lateralis Preparata are potential candidates for the treatment of myocardial infarction.
Assuntos
Aconitum/química , Cardiotônicos/farmacologia , Coração/efeitos dos fármacos , Miocárdio/metabolismo , Extratos Vegetais/farmacologia , Animais , Cardiotônicos/química , Metabolismo Energético/efeitos dos fármacos , Metabolômica/métodos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Extratos Vegetais/química , Ratos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Relação Estrutura-AtividadeRESUMO
We used Box-Behnken design-based (BBD) response surface methodology (RSM) in this research to optimize the extraction process of Traditional medicine Majun Mupakhi Ela (MME) and evaluate its effect on hydrocortisone-induced kidney yang deficiency. Three independent parameters were applied to evaluate the maximum phosphodiesterase type 5 (PDE5) inhibition activity of MME extracts in vitro. The optimal processing conditions (extraction time 2 h, solid-liquid ratio 1:16, extraction once) gave a maximum PDE5 inhibition rate of 84.10%, flavonoid content of 0.49 mg/ml, icariin content of 0.028 mg/ml and targeted extraction yield of 26.50%. In animal experiments, MME extracts significantly increased the adrenal mass index, semen weight index, preputial gland weight index, and penis weight index in mice; in the middle and high dose group, the level of serum testosterone increased by 7664.29% and 14207.14% respectively, compared with the model group, and the level of PDE5 decreased by 67.22% and 74.69% respectively compared with the control group. These results indicate that MME has a significant positive effect on the hypothalamus-pituitary-gonadal axis, improve mating ability and not only has inhibits PDE5 activity but also significantly inhibits the expression of PDE5 in penile tissues, potential to become erectile dysfunction (ED) therapies for the clinical management of patients with kidney yang deficiency.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/métodos , Animais , China , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Medicamentos de Ervas Chinesas/química , Disfunção Erétil/fisiopatologia , Hidrocortisona/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pênis/metabolismo , Inibidores da Fosfodiesterase 5/química , Inibidores da Fosfodiesterase 5/isolamento & purificação , Deficiência da Energia Yang/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Swertia punicea Hemsl. (Gentianaceae) is more commonly known as "Ganyan-cao" and used mainly as a traditional Chinese folk medicine for the treatment of acute bilious hepatitis, cholecystitis, fever, intoxification and jaundice. MATERIALS AND METHODS: The active hepatoprotective constituents of Swertia punicea were purified using various column chromatography techniques. The structures of two isolated compounds were determined on the basis of spectroscopic data interpretation such as NMR analysis. The hepatoprotective activities of isolated compounds were evaluated by using hepatotoxicity in vitro and dimethylnitrosamine-induced rat hepatic fibrosis in vivo, respectively. RESULTS: Two xanthones, 1, 7-dihydroxy-3, 4, 8-trimethoxyxanthone (1) and bellidifolin (2) were isolated from the stems of Swertia punicea. The compounds 1 and 2 exhibited notable hepatoprotective activities against carbon tetrachloride (CCl4) -induced HepG2 cell damage, and effectively alleviated the levels of aspartate transaminase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malonic dialdehyde (MDA) induced by CCl4 in a concentration-dependent manner. Co-treatment with compound 2 significantly increased the cell viability compared with N-acetyl-p-aminophenol (APAP) treatment. Compound 2 also alleviated APAP-induced hepatotoxicity by increasing glutathione (GSH) content and decreasing hydroxyl free radical (·OH) levels and reactive oxygen specises (ROS) production. In addition, the protective effect of compound 1 significantly alleviated DMN-induced liver inflammation and fibrosis. Oral administration of compound 1 recovered the reduction of albumin (ALB) and reversed the elevation of serum alanine transaminase (ALT), AST and total bilirubin (TBIL) in dimethylnitrosamine (DMN)-induced fibrotic rats. Severe oxidative stress induced in fibrotic rats was evidenced by a 1.5-fold elevation in MDA and a fall in the SOD activity, and treatment with compound 1 protected against these adverse effects. Recovery of rat liver tissue against DMN-induced hepatocellular necrosis, inflammatory changes and hepatic fibrosis by compound 1 is also confirmed by H&E and Masson stained histopathological evaluation of liver tissue. CONCLUSION: Two xanthones from Swertia punicea exhibited hepatoprotective activities in vitro (compounds 1 and 2) and in vivo (compound 1), respectively.
Assuntos
Substâncias Protetoras , Swertia , Xantonas , Acetaminofen , Animais , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/metabolismo , Bilirrubina/sangue , Tetracloreto de Carbono , Sobrevivência Celular/efeitos dos fármacos , Dimetilnitrosamina , Glutationa/metabolismo , Células Hep G2 , Humanos , L-Lactato Desidrogenase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Albumina Sérica/análise , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo , Xantonas/isolamento & purificação , Xantonas/farmacologia , Xantonas/uso terapêuticoRESUMO
Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of many respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). To evaluate the treatment responses of procaterol and CD38 inhibitors in an ozone-induced AHR mice model, we hypothesized that procaterol and two synthetic CD38 inhibitors (Compounds T and H) might have therapeutic effects on the ozone-induced AHR mice model, and the nuclear factor-kappaB (NF-κB) pathway and the CD38 enzymatic activity might be involved in the mechanisms. With the exception of the Control group, ozone exposure was used to establish an AHR model. Male Kunming mice in the Procaterol and CD38 inhibitors groups were treated with an emulsifier of procaterol hydrochloride, Compound T or H. Results indicated that (1) no drug showed severe toxicity in this study; (2) ozone exposure induced airway inflammation and AHR; (3) intragastric treatment with procaterol and Compound T achieved potent therapeutic effects, but Compound H did not show any therapeutic effect; (4) the NF-κB pathway was involved in both the pathogenic mechanisms of ozone and therapeutic mechanisms of procaterol and Compound T; (5) however, the in vivo effect of Compound T was not caused by its inhibitory activity on CD38. Taken together, procaterol and Compound T are potentially good drugs to treat asthma and COPD complicated with ozone exposure.
Assuntos
Antiasmáticos/uso terapêutico , Benzoatos/uso terapêutico , Hiper-Reatividade Brônquica/tratamento farmacológico , Indóis/uso terapêutico , Procaterol/uso terapêutico , ADP-Ribosil Ciclase 1/antagonistas & inibidores , Animais , Antiasmáticos/farmacologia , Benzoatos/farmacologia , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/patologia , Hiper-Reatividade Brônquica/fisiopatologia , Testes de Provocação Brônquica , Líquido da Lavagem Broncoalveolar/citologia , Modelos Animais de Doenças , Indóis/farmacologia , Contagem de Leucócitos , Pulmão/imunologia , Pulmão/patologia , Masculino , Glicoproteínas de Membrana/antagonistas & inibidores , Cloreto de Metacolina , Camundongos , NF-kappa B/imunologia , Ozônio , Procaterol/farmacologiaRESUMO
Parkinson disease (PD) is the second most common neurodegenerative disease, and it cannot be completely cured by current medications. In this study, DJ-1 protein was administrated into medial forebrain bundle of PD model rats those had been microinjected with 6-hydroxydopamine (6-OHDA) or MG-132. We found that DJ-1 protein could reduce apomorphine-induced rotations, inhibit reduction of dopamine contents and tyrosine hydroxylase levels in the striatum, and decrease dopaminergic neuron death in the substantia nigra. In 6-OHDA lesioned rats, uncoupling protein-4, uncoupling protein-5 and superoxide dismutase-2 (SOD2) mRNA and SOD2 protein were increased when DJ-1 protein was co-injected. Simultaneously, administration of DJ-1 protein reduced α-synuclein and hypoxia-inducible factor 1α mRNA and α-synuclein protein in MG-132 lesioned rats. Therefore, DJ-1 protein protected dopaminergic neurons in two PD model rats by increasing antioxidant capacity and inhibiting α-synuclein expression.
Assuntos
Antiparkinsonianos/uso terapêutico , Neurônios Dopaminérgicos/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/uso terapêutico , Leupeptinas/toxicidade , Fármacos Neuroprotetores/uso terapêutico , Proteínas Oncogênicas/uso terapêutico , Oxidopamina/toxicidade , Transtornos Parkinsonianos/prevenção & controle , Animais , Antiparkinsonianos/administração & dosagem , Apomorfina/antagonistas & inibidores , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Dopamina/análise , Neurônios Dopaminérgicos/enzimologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Peptídeos e Proteínas de Sinalização Intracelular/administração & dosagem , Canais Iônicos/biossíntese , Canais Iônicos/genética , Masculino , Microinjeções , Proteínas de Transporte da Membrana Mitocondrial/biossíntese , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas Mitocondriais/biossíntese , Proteínas Mitocondriais/genética , Proteínas de Desacoplamento Mitocondrial , Atividade Motora/efeitos dos fármacos , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Fármacos Neuroprotetores/administração & dosagem , Proteínas Oncogênicas/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/tratamento farmacológico , Proteína Desglicase DJ-1 , Ratos , Ratos Sprague-Dawley , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia , Superóxido Dismutase/biossíntese , Superóxido Dismutase/genética , Tirosina 3-Mono-Oxigenase/análise , alfa-Sinucleína/biossíntese , alfa-Sinucleína/genéticaRESUMO
In the present study, we investigated the neuroprotective effects of kaempferol in the mouse model of Parkinson's disease, which was induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We confirmed that MPTP led to behavioral deficits, depletion of dopamine and its metabolites, reduction in superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, and the elevation of malondialdehyde (MDA) levels in the substantia nigra. When administered prior to MPTP, kaempferol improved motor coordination, raised striatal dopamine and its metabolite levels, increased SOD and GSH-PX activity, and reduced the content of MDA compared with mice treated with MPTP alone. Immunohistochemical studies using anti-tyrosine hydroxylase (TH) antibody showed that medication of kaempferol could prevent the loss of TH-positive neurons induced by MPTP. Taken together, we propose that kaempferol has shown anti-parkinsonian properties in our studies. More work is needed to explore detailed mechanisms of action.
Assuntos
Antioxidantes/uso terapêutico , Quempferóis/uso terapêutico , Intoxicação por MPTP/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Ataxia/induzido quimicamente , Ataxia/tratamento farmacológico , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Glutationa Peroxidase/metabolismo , Quempferóis/farmacologia , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Extratos Vegetais/farmacologia , Superóxido Dismutase/metabolismoRESUMO
DJ-1 was identified as a causal gene for a familial form of early onset Parkinson's disease (PD), park 7. DJ-1 plays roles in transcriptional regulation and the anti-oxidative stress reaction. In this study, we found that protocatechuic aldehyde (PAL), a traditional Chinese medicine compound, bound to DJ-1 in vitro and that PAL protected SH-SY5Y cells but not DJ-1-knockdown SH-SY5Y cells from oxidative stress-induced cell death, indicating that the protective effect of PAL is mediated by DJ-1. Furthermore, PAL inhibited production of reactive oxygen species and the inhibition was abated in DJ-1-knockdown cells. PAL increased and decreased phosphorylation of AKT and PTEN, respectively, in SH-SY5Y cells, suggesting that the AKT pathway is one of the specific signaling pathways in PAL-induced neuroprotection. Moreover, PAL prevented superfluous oxidation of cysteine 106 of DJ-1, an essential amino acid for DJ-1's function. The present study demonstrates that PAL has potential neuroprotective effects through DJ-1.
Assuntos
Benzaldeídos/farmacologia , Catecóis/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Neuroblastoma/patologia , Fármacos Neuroprotetores , Proteínas Oncogênicas/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Tirosina Quinase da Agamaglobulinemia , Benzaldeídos/metabolismo , Catecóis/metabolismo , Morte Celular/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Oncogênicas/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Doença de Parkinson/genética , Fosforilação , Ligação Proteica , Proteína Desglicase DJ-1 , Proteínas Tirosina Quinases/metabolismo , Proteínas Tirosina Quinases/fisiologia , Transdução de Sinais , Células Tumorais CultivadasRESUMO
Xanthone compounds have been reported to inhibit cancer cell growth as well as possessing antioxidant properties. The xanthone compound 3-O-demethylswertipunicoside (3-ODS), extracted from Swertia punicea HEMSL, has not previously been demonstrated to have clear neuroprotective effects. In our study, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell death assay revealed that treatment of PC12 cells with 3-ODS ameliorated the decreased cell viability induced by exposure to 1-methyl-4-phenylpyridinium ion (MPP+), rotenone or H2O2. The acridine orange/ethidium bromide (AO/EB) apoptosis assay demonstrated a significant suppression of cell death in PC12 cells. by 3-ODS treatment. 3-ODS increased the protein expression of both tyrosine hydroxylase (TH) and DJ-1 expression in PC12 cells. The current study demonstrates that 3-ODS has potential neuroprotective effects mediated via the elevation of TH and DJ-1 protein levels.
Assuntos
Citoproteção/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Swertia , Xantonas/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Citoproteção/fisiologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Estresse Oxidativo/fisiologia , Células PC12 , Ratos , Xantonas/química , Xantonas/isolamento & purificaçãoRESUMO
Two new dimeric xanthone O-glycosides, puniceasides A (1) and B (2), a new trimeric O-glycoside, puniceaside C (3), and two new trimeric C-glycosides, puniceasides D (4) and E (5), together with 12 known xanthones were isolated from the entire plant of Swertia punicea. The structures of 1-5 were determined by HRESIMS and NMR spectroscopic methods. Compounds 2, 6, and 7 exhibited potent neuroprotective activity against H(2)O(2)-induced PC12 cell damage.
Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Swertia/química , Xantonas/isolamento & purificação , Xantonas/farmacologia , Animais , Medicamentos de Ervas Chinesas/química , Glicosídeos/química , Peróxido de Hidrogênio/farmacologia , Estrutura Molecular , Fármacos Neuroprotetores/química , Ressonância Magnética Nuclear Biomolecular , Células PC12 , Ratos , Xantonas/químicaRESUMO
DJ-1, a causative gene product of a familial form of Parkinson's disease (PD), PARK7, plays a role in anti-oxidative stress, and loss of its function is thought to result in the onset of PD. Superfluous oxidation of cysteine at amino acid 106 (C106) of DJ-1 renders DJ-1 inactive, and such oxidized DJ-1 was observed in patients with the sporadic form of PD. In this study, we examined the relationship between DJ-1 and compounds extracted from traditional Chinese medicines possessing anti-oxidant activity. Of the 12 compounds tested, 5 were found to specifically bind to the C106 region by using a quartz crystal microbalance. Although 4 compounds prevented rat PC12 and primary neuronal cells from undergoing H2O2-induced cell death, the protective activity of 2 compounds, kaempferol 3-O-beta-rutinoside and 6-hydroxykaempferol 3,6-di-O-beta-D-glucoside, was diminished in cells transfected with siRNA targeting DJ-1, indicating DJ-1-dependent reaction of these compounds. Furthermore, these compounds reduced the level of reactive oxygen species and restored tyrosine hydroxylase activity that had been induced and compromised, respectively, by treatment of cells with H2O2. The results suggest that these compounds are useful lead compounds for PD therapy.
Assuntos
Antioxidantes/farmacologia , Quempferóis/farmacologia , Proteínas Associadas aos Microtúbulos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/isolamento & purificação , Carthamus/química , Morte Celular/efeitos dos fármacos , Peróxido de Hidrogênio/administração & dosagem , Quempferóis/isolamento & purificação , Medicina Tradicional Chinesa , Proteínas Associadas aos Microtúbulos/metabolismo , Células PC12 , Proteína Desglicase DJ-1 , RNA Interferente Pequeno/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Tirosina 3-Mono-Oxigenase/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Investigations of two Flacourtiaceae plants, Bennettiodendron leprosipes and Flacourtia ramontchi, resulted in the isolation and structural elucidation of six new constituents including two phenolic glycosides ( 1 and 2), one lignan ( 3), two lignan glycosides ( 4 and 5), and a monoterpene glycoside ( 6), together with 22 known compounds ( 7- 28). The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. The selected isolates 1, 2, 8- 10, 22- 26, and some phenolic glycosides 29- 42 previously isolated from another Flacourtiaceae plant, Itoa orientalis, were tested against snake venom phosphodiesterase I (PDE I) activity. The result indicated that 22, 30, 32, 34, and 40 exhibited moderate inhibitory activities against PDE I with the values ranging from 13.15 to 20.86 %, and 1, 8, 10, 25, 31, 33, 35, 38, 39, and 41 showed weak inhibitory activity.
Assuntos
Salicaceae/química , Antivenenos/química , Antivenenos/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Lignanas/química , Lignanas/isolamento & purificação , Monoterpenos/química , Monoterpenos/isolamento & purificação , Fenóis/química , Fenóis/isolamento & purificação , Fosfodiesterase I/antagonistas & inibidores , Venenos de Serpentes/antagonistas & inibidoresRESUMO
Parkinson's disease is characterized by the progressive degeneration of midbrain dopaminergic neurons. Buddleia lindleyana is a traditional Chinese herb, commonly called Zui Yu Cao. The purification and identification of pedicularioside A and other phenylethanoid glycosides from this plant have been reported. However, their neuroprotective effects on the 1-methyl-4-phenylpyridinium ion (MPP(+))-induced death of rat mesencephalic neuron primary cultures and the precise mechanism of this protection remains unclear. We used the 3-(4, 5-dimethylthiozol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay for cellular growth to examine the effects of five phenylethanoid glycosides isolated from B. lindleyana, including pedicularioside A, leucosceptoside A, isoacteoside, acteoside, and arenariside, on the viability of mesencephalic neurons treated with MPP(+). Of the compounds tested, pedicularioside A exhibited the greatest degree of protection from MPP(+)-induced cell death. We also observed a marked increase in the number of tyrosine hydroxylase immunoreactive neurons. Pedicularioside A inhibited expression of the caspase-3 gene and cleavage of poly (ADP-ribose) polymerase (PARP) in cultures exposed to MPP(+). Our results suggest that pedicularioside A has a neuroprotective effect to improve the survival of mesencephalic neurons (dopaminergic neurons and non-dopaminergic neurons). The mode of action appears to be the inhibition of caspase-3 gene expression, thereby protecting mesencephalic neurons from MPP(+)-induced cell death.
Assuntos
Buddleja/química , Morte Celular/efeitos dos fármacos , Glucosídeos/farmacologia , Iridoides/farmacologia , Fármacos Neuroprotetores/farmacologia , 1-Metil-4-fenilpiridínio/toxicidade , Animais , Caspase 3/efeitos dos fármacos , Caspase 3/genética , Sobrevivência Celular/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glucosídeos/isolamento & purificação , Glucosídeos Iridoides , Iridoides/isolamento & purificação , Medicina Tradicional Chinesa , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/isolamento & purificação , Doença de Parkinson/tratamento farmacológico , Poli(ADP-Ribose) Polimerases/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos , Ratos Wistar , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
In our study we investigated the neuroprotective effects of phenylethanoid glycosides (PhGs) from Cistanches salsa on 1-methyl-4-phenylpyridinium ion (MPP(+))-induced apoptosis in cerebellar granule neurons (CGNs). CGNs were treated with 100 microM MPP(+) for 24h to induce apoptosis, simultaneously CGNs were incubated with PhGs at 10, 20 and 40 microg/ml, respectively. In addition CGNs were pretreated with PhGs at 20 microg/ml for 6, 12, 24 h, respectively, and then treated with 100 microM MPP(+) for 24 h. 3-(4,5-Dimethylthiazol-2-ylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that the treatment of CGNs with PhGs inhibited the decrease of cell viability induced by MPP(+). The activation of caspase-3 and caspase-8 was induced by MPP(+) in apoptosis. The caspase-3 and caspase-8 fluorogenic assays showed that the treatments of CGNs with PhGs efficiently suppressed the activation of caspase-3 and caspase-8 induced by MPP(+). It is concluded that PhGs can prevent the MPP(+)-induced apoptosis in CGNs and exert its anti-apoptosis effect by inhibiting caspase-3 and caspase-8 activities.
Assuntos
1-Metil-4-fenilpiridínio/toxicidade , Apoptose/efeitos dos fármacos , Cistanche , Glicosídeos/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Animais , Apoptose/fisiologia , Inibidores de Caspase , Caspases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Glicosídeos/isolamento & purificação , Neurônios/enzimologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Caules de Planta , Ratos , Ratos WistarRESUMO
The neuroprotective effects of verbascoside, one of phenylpropanoid glucoside isolated from the Chinese herbal medicine Buddleja officinalis Maxim, on 1-methyl-4-phenylpyridinium ion (MPP(+)) induced apoptosis and oxidative stress in PC12 neuronal cells were investigated. Treatment of PC12 cells with MPP(+) for 48 h induced apoptotic death as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, the activation of caspase-3 measured by the caspase-3 activity assay kit, the reduction in mitochondrial membrane potential with laser scanning confocal microscopy and the increase in the extracellular hydrogen peroxide level. Simultaneous treatment with verbascoside markedly attenuated MPP(+)-induced apoptotic death, increased extracellular hydrogen peroxide level, the activation of caspase-3 and the collapse of mitochondrial membrane potential. These results strongly indicate that verbascoside may provide a useful therapeutic strategy for the treatment of oxidative stress-induced neurodegenerative disease such as Parkinson's disease.