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1.
Front Pharmacol ; 14: 1115387, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36843923

RESUMO

Radix Rehmanniae Praeparata (RRP, Shu Dihuang in Cinese) is widely used as primal medicine in Chinese herbal formula for the treatment of Alzheimer's disease (AD). However, the underlying mechanism of RRP for AD remains unclear. The aim of this study was to investigate the therapeutic effect of RRP on intracerebroventricular injection of streptozotocin (ICV-STZ)-induced AD model mice and its potential mechanism. ICV-STZ mice were continuously gavaged with RRP for 21 days. The pharmacological effects of RRP were evaluated by behavioral tests, brain tissue H&E staining and hippocampal tau protein phosphorylation levels. The expression levels of insulin receptor (INSR), IRS-1, pSer473-AKT/AKT and pSer9-GSK-3ß/GSK-3ß proteins in hippocampal and cortical tissues were detected by Western-blot method. The 16S rRNA gene sequencing was used to analyze the changes of intestinal microbiota in mice. The compounds in RRP were analyzed by mass spectrometry and their binding ability to INSR proteins was detected by molecular docking. The results showed that RRP ameliorated cognitive dysfunction and neuronal pathological changes of brain tissue in ICV-STZ mice, reduced tau protein hyperphosphorylation, INSR, IRS-1, pSer473-AKT/AKT, and pSer9-GSK-3ß/GSK-3ß levels in hippocampal and cortical tissues. Meanwhile, RRP reversed ICV-STZ-induced dysregulation of intestinal microbiota in AD mice. Mass spectrometry analysis showed that the RRP consisted mainly of seven compounds, namely Acteoside (Verbascoside), 5-Hydroxymethyl-2-furaldehyde (5-HMF), Apigenin7-O-glucuronide, Icariin, Gallic acid, Quercetin-3ß-D-glucoside, and Geniposide. Molecular docking results further indicated that the compounds in RRP have binding ability to INSR protein and potential multiple synergistic effects. RRP ameliorates cognitive dysfunction and brain histopathological changes in AD mice. The mechanism of RRP ameliorating AD may be related to the regulation of INSR/IRS-1/AKT/GSK-3ß signaling pathway and intestinal microbiota. This study supports the potential anti-AD efficacy of RRP and initially reveals the pharmacological mechanism of RRP, providing a theoretical basis for further clinical application of RRP.

2.
J Ethnopharmacol ; 296: 115491, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35752263

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: LiuweiDihuang (LW) pills was mainly used to treatment of children's fontanelle incomplete closure, enuresis and nervous system development delays and other diseases.Following the deepening of pharmacological research, LW has a good effect on neurological diseases include senile dementia. However, the neuroprotection mechanism of LW on Alzheimer's disease (AD) through regulation of inflammation remains unclear. AIM OF THE STUDY: Here, we aimed to explore the effects and mechanism of LW on learning and memory deficits in SAMP8 mice. MATERIALS AND METHODS: Mice aged 6 months were treated with LW for 2 months and BV2, C6 and HT22 cells were treated with LW pharmaceutic serum and Lipopolysaccharide (LPS) continuously. Then, cognitive tests were performed, including the Morris water maze and Y maze tests. The mRNA level of cyclooxygenase 2 (COX-2) and pro-inflammatory factors (IL-1ß, IL-6 and TNF-α) were examined in cells and the cortex and hippocampus by quantitative RT-PCR. The expression of postsynaptic density protein 95, synaptophysin and various inflammatory factors were detected in the cortex and hippocampus by Western blot. Furthermore, Ionized calcium binding adapter molecule 1, glial fibrillary acidic protein and Aß were examined in the brain of AD mice by immunofluorescence staining and immunohistochemistry. And synaptic loss and neuronal ultrastructure were observed by transmission electron microscope. RESULTS: We found that LW suppressed LPS-induced COX-2 expression in vitro. Importantly, LW dramatically improved spatial learning and memory in SAMP8 mice through inhibiting Aß accumulation and restoring structural synaptic integrity. Furthermore, LW inhibited the glial activation and neuroinflammation (COX-2, IL-1ß, IL-6 and TNF-α) in the cortex and hippocampus of SAMP8 mice. CONCLUSION: Taken together, the present data not only indicated that LW is an effective agent on improving the learning and memory deficits through mitigating neuroinflammation but highlighted the LW can be a potential therapeutic drug for AD therapy.


Assuntos
Doença de Alzheimer , Cognição , Ciclo-Oxigenase 2 , Lipopolissacarídeos , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Cognição/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/química , Modelos Animais de Doenças , Hipocampo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Doenças Neuroinflamatórias/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo
3.
Fitoterapia ; 147: 104730, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32971205

RESUMO

One new bisesquiterpenoid, biepiasreorlid II (1), three new sesquiterpene lactones 8α-methoxy-epiasterolid (4), 3ß-acetoxyl-8-epiasterolid (5), and 3ß-acetoxyl-atractylenolide I (6), along with five known analogues (2-3 and 7-9), were obtained from rhizome of Atractylodes macrocephala Koidz. All structures were assigned on the basis of detailed spectroscopic analyses. The absolute configuration of 1 was established by the analysis of single-crystal X-ray diffraction with Ga Kα radiation, and 4-6 were elucidated by TDDFT-ECD calculations. The CREB agonistic activity was investigated in HEK293T cells using dual luciferase reporter assay. Compounds 1, 2, 5, and 7-9 exhibited strong to agonistic activities on CREB.


Assuntos
Atractylodes/química , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/antagonistas & inibidores , Lactonas/farmacologia , Sesquiterpenos/farmacologia , China , Células HEK293 , Humanos , Lactonas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Rizoma/química , Sesquiterpenos/isolamento & purificação
4.
Pharmacology ; 103(3-4): 128-135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30544104

RESUMO

OBJECTIVES: To measure the expression of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinase inhibitor (TIMP)-2, and CD147 in mice with chronic liver injury induced by carbon tetrachloride after treatment with the traditional Chinese medicine (TCM) "Compound T11". METHOD: Sixty male ICR mice were divided randomly into 6 groups of 10: control (C), model (M), low-dose treatment (LT; 50 mg/mL of Compound T11), medium-dose treatment (MT, 100 mg/mL), high-dose treatment (HT, 150 mg/mL), and positive drug treatment (YT, 67.5 mg/mL). Each group was modeled for 7 weeks. Groups M, LT, MT, HT, and YT were injected (s.c.) with 20% carbon tetrachloride diluted with olive oil, and group C was given olive oil in the same way twice a week. After modeling, the treatment groups were administered Compound T11 at the concentrations shown above by oral gavage daily for 2 weeks, while group C was given 0.5% carboxymethyl cellulose sodium. After the final treatment, mice were killed and their liver tissues were excised. Immunohistochemical staining was performed to measure the protein expression of MMP-2, TIMP-2, and CD147, and western blotting was used to measure the protein expression of MMP-2, TIMP-2, CD147, and α-smooth muscle actin (SMA). MMP-2, TIMP-2, and CD147 mRNA expression was determined by quantitative fluorescence real-time PCR. RESULTS: Compound T11 increased the protein expression of MMP-2 and CD147 and decreased the protein expression of TIMP-2 and α-SMA. CONCLUSIONS: Treatment of chronic liver injury by TCM Compound T11 may be associated with changes to the expression of MMP-2 and CD147, and the inhibition of TIMP-2 expression.


Assuntos
Basigina/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática Experimental/prevenção & controle , Fígado/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Animais , Basigina/genética , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citoproteção , Relação Dose-Resposta a Droga , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/enzimologia , Cirrose Hepática Experimental/patologia , Masculino , Metaloproteinase 2 da Matriz/genética , Camundongos Endogâmicos ICR , Fatores de Tempo , Inibidor Tecidual de Metaloproteinase-2/genética
5.
J AOAC Int ; 102(2): 451-456, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30305199

RESUMO

Background: The green tea scraps are the waste materials during the process of green tea production, and it is significant to extract valuable tea polyphenols (TP) for reuse. Objective: The objective of this study was to extract valuable TP from green tea scraps, and the extraction conditions were optimized to obtain maximum yield of TP. Methods: The TP were extracted by supercritical carbon dioxide (SC-CO2) with 65% (v/v) aqueous ethanol solution as cosolvent. The content of TP was determined with the Folin-Ciocalteu method. The key factors of the extraction process, including temperature (313.15-323.15 K), pressure (20-30 Mpa), and amount of cosolvent (50-150 mL) were optimized by response surface methodology (RSM). Results: These key factors showed the extremely complex effects on the extraction yield of TP. A second-order polynomial mathematical model was developed for the response with high R-squared value (R² = 0.9946) and used to predict the optimal conditions (i.e., temperature of 322.15 K, pressure of 23.60 MPa, and amount of cosolvent of 150 mL). The verification experiments showed that the maximum yield of TP was 23.07 ± 0.82% under the optimal conditions, which was in good agreement with the predicted value. Conclusions: TP can be successfully extracted from green tea scraps by SC-CO2, and RSM could be used to optimize the extraction process. Highlights: SC-CO2 extraction of TP from green tea scraps was developed. The operating conditions, including pressure, temperature, and amount of cosolvent, were optimized. RSM could successfully predict the optimal operating conditions.


Assuntos
Dióxido de Carbono/química , Cromatografia com Fluido Supercrítico , Polifenóis/isolamento & purificação , Chá/química , Polifenóis/química , Propriedades de Superfície
6.
J Ethnopharmacol ; 133(2): 448-53, 2011 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-20951784

RESUMO

AIM OF THE STUDY: Panaxatriol saponins (PTS), the main constituents extracted from Panax notoginseng, a Chinese herbal medicine, has been shown to be an effective agent on various diseases. Our previous study has demonstrated that PTS is an inducer of thioredoxin-1 (Trx-1) and has a possible potential as a therapeutic agent for Parkinson's disease (PD). However, the effect of PTS on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in vivo is unknown. MATERIALS AND METHODS: Using locomotor activity test and traction test, we detected the effect of PTS on MPTP-induced behavioral impairment. Tyrosine hydroxylase, Trx-1, cyclooxygenase-2, pro-caspase-9, pro-caspase-12 and caspase-3 expressions in the anatomical region of substantia nigra pars compacta (SNc) were tested by Western blot. RESULTS: PTS provided neuroprotection against the loss of dopaminergic neurons and behavioral impairment caused by MPTP. MPTP-induced neuronal death in the SNc was suppressed by PTS through increasing Trx-1 expression, suppressing cyclooxygenase-2 over-expression and inhibiting mitochondria-mediated apoptosis. CONCLUSIONS: PTS, an inducer of Trx-1, has pluripharmacological properties in the protection against PD including enhancing antioxidant activity, acting as neurotrophic factor, modulating inflammation and inhibiting mitochondria-mediated apoptosis.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Ginsenosídeos/farmacologia , Intoxicação por MPTP/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Panax notoginseng/química , Saponinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 12/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , China , Ciclo-Oxigenase 2/metabolismo , Medicamentos de Ervas Chinesas/química , Precursores Enzimáticos/metabolismo , Etnofarmacologia , Ginsenosídeos/isolamento & purificação , Intoxicação por MPTP/enzimologia , Intoxicação por MPTP/patologia , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Neurotoxinas/toxicidade , Saponinas/isolamento & purificação , Substância Negra/efeitos dos fármacos , Substância Negra/enzimologia , Substância Negra/patologia , Tirosina 3-Mono-Oxigenase/metabolismo
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