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1.
J Ethnopharmacol ; : 113583, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33189845

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shizaotang (SZT), consisted of Euphorbia kansui S.L.Liou ex S.B.Ho (EK), Euphorbia pekinensis Rupr. (EP), Daphne genkwa Sieb. et Zucc. (DG,fried) and Ziziphus jujuba Mill. (ZJ), is usually used for treating malignant pleural effusions (MPE), but the toxicity of EK and EP limits its clinical safe application. It was reported that vinegar processing can reduce the toxicity of EK and EP. Whether EK and EP processing with vinegar can cause the reduced toxicity and retained pharmacological effects of SZT, it still remains unknown. AIM OF THE STUDY: We aimed to evaluate whether using vinegar processed EK and EP would reduce toxicity and preserve water expelling effect of SZT. MATERIALS AND METHODS: Network pharmacology and qualitative analysis of SZT/VSZT were used to construct compound-target-pathway network of their effects and toxicity. Pleural fluid weight, urine volume, uric electrolyte, pH, pro-inflammatory cytokines in pleural fluid, serum Renin-Angiotensin-Aldosterone System (RAAS), anti-diuretic hormone (ADH) and intestinal aquaporin 8 (AQP8) protein were used to evaluate the effect mechanisms involved in rats experiments. And liver damage, oxidative damage and HE staining (liver, stomach, and intestine) were used to determine the toxicity. RESULTS: Network pharmacology analysis reviewed inflammation-related pathways of the effect and toxicity of SZT/VSZT: VEGF-PI3K-AKT pathway inhibited MPE by changing the vasopermeability; PI3K-Akt/Mitogen-activated protein kinase (MAPK)/TNF-NF-κB signaling pathway inhibited MPE by up-regulating expression of AQP8 protein. In vivo experiments displayed that SZT/VSZT could reduce pleural fluid, increase urine volume, lower pro-inflammatory cytokines levels and up-regulate AQP8 protein expression significantly (P < 0.05, P < 0.01). In addition, disorders on electrolyte (Na+, K+ and Cl-) and pH were ameliorated (P < 0.05, P < 0.01). The levels of RAAS and ADH were significantly dose-dependently called back (P < 0.01). These findings were partly consistent with the results of network pharmacology analysis. Results of toxicity experiments demonstrated that SZT and VSZT exhibited certain toxicity on normal rats, and VSZT had lower toxicity than that of SZT. Interestingly, SZT and VSZT exerted alleviation effect to the liver damage and oxidative damage on model rats. CONCLUSION: SZT/VSZT improved MPE by regulating associated inflammation pathways. Besides, compared to SZT, VSZT showed lower toxicity and equivalent expelling MPE effect. This study may provide scientific basis for guiding the clinical application of SZT.

2.
Front Microbiol ; 11: 1489, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013716

RESUMO

Plant seeds are not merely reproductive organs, they are also carriers of microorganism, particularly, inherent and non-invasive characteristic endophytes in host plant. Therefore, in this study, the endophytic diversity of Angelica seeds was studied and compared with endophytes isolated from healthy leaves, stems, roots, and seeds of A. sinensis using 20 different media. The metabolites of endophytic strains were evaluated with six different methods for their antioxidant activity and the paper disc diffusion method for antimicrobial activities. As a result, 226 endophytes were isolated. Compared with the biodiversity and abundance of uncultured fungi from Angelica seed, the result showed that the most frequent endophytic fungi were Alternaria sp. as seen in artificial media; moreover, compared with artificial media, the pathogenic fungi, including Fusarium sp. and Pseudallescheria sp., were not found from the Angelica seed, the results suggested it may not be inherent endophytes in plants. In addition, bacteria from seven phyla were identified by high-throughput sequencing, while five phyla of endophytic bacteria were not isolated on artificial media including Proteobacteria, Actinobacteria, Bacteroidetes, Microgenomates, and Saccharibacteria. Furthermore, the sample JH-4 mycelium displayed the best antioxidant activity, and the active constituent may be a flavonoid as determined by total phenol and flavonoid content. Moreover, YH-12-1 mycelium had strong inhibitory activity against the five tested strains and the minimum inhibitory concentration (MIC) against Pseudomonas aeruginosa and Streptococcus pneumoniae was found to be 25 µg/mL. Our results confirm that plant endophytes are rich in biodiversity and contain important resource of many uncultured microorganisms.

3.
Prep Biochem Biotechnol ; : 1-11, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32820988

RESUMO

Endophytes may depend on degrading the plant cell wall with cellulases for their survival. Therefore, cellulase produced by endophytes may be useful in releasing the active ingredient of medicinal plants. Scutellaria baicalensis Georgi is a traditional Chinese medicinal plant widely used in China and baicalin is one of its main active ingredients. In this study, fresh S. baicalensis Georgi was used to isolate endophytes, Congo red staining was used to screen cellulase-producing strains, and HPLC was used to determine the content of baicalin in S. baicalensis Georgi. As a result, a highly active strain of endophyte capable of the extraction of high levels of baicalin was obtained. The strain was named HG-5 and identified as Bacillus sp. Scanning electron microscopy analysis confirmed that the enzyme better promotes the dissolution of plant active ingredients. After optimizing the enzyme production and extraction processes, we found that when compared with the traditional extraction method, the baicalin yield was increased 79.31% after extraction with the HG-5 enzyme. The current study provides a novel approach and method for the use of endophyte cellulase to improve the extraction of compounds from medicinal plants.

4.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1452-1459, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281360

RESUMO

To reveal the toxic mechanism of Kansui stir-baked with vinegar(VEK), conducta comparative study on the metabolites of fecal samples of rats before and after being treated with chemical constituents group B and C(VEKB/VEKC) extracted from VEK by metabolomics approach. The fecal samples of each group were analyzed using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UFLC-Q-TOF-MS). Then the data was processed by principal component analysis(PCA) and partial least square discriminant analysis(OPLS-DA) to screen and identify biomarkers relating to the toxicity of VEK. Besides, t-test was adopted for univariate statistical analysis, so as to study the changes of these biomarkers in drug groups before and after being treated with VEKB/VEKC and explore the effect of VEKB/VEKC on the metabolism of rat feces. Furthermore, the toxic mechanism of VEKB/VEKC was explored based on the results of the metabolic pathway analysis. The results displayed that compared with control group, the metabolism of fecal samples of VEKB and VEKC treated groups show obvious changes, and the VEKB treated group show more significant changes. A total of 16 potential biomarkers and 5 metabolic pathways relating to the toxicity of VEK were found and identified. And the toxicity of VEK might be associated with the disorder of such metabolic pathways as tryptophan metabolism, primary bile acid biosynthesis, amino sugar and nucleotide sugar metabolism, purine metabolism, and degradation of valine, leucine and isoleucine. This study provides a scientific basis for the clinical safety application of VEK.


Assuntos
Ácido Acético , Euphorbia/química , Fezes/química , Metaboloma , Animais , Biomarcadores , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Ratos
5.
Folia Microbiol (Praha) ; 65(2): 293-302, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31273645

RESUMO

Medicinal plants have been studied for potential endophytic interactions and numerous studies have provided evidence that seeds harbor diverse microbial communities, not only on their surfaces but also within the embryo. Adenosine deaminase (ADA) is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Therefore, in this study, 20 types of medicinal plant seeds were used to screen endophytic fungi with tissue homogenate and streak. In addition, 128 morphologically distinct endophyte strains were isolated and their ADA inhibitory activity determined by a spectrophotometric assay. The strain with the highest inhibitory activity was identified as Cochliobolus sp. Seven compounds were isolated from the strain using a chromatography method. Compound 3 showed the highest ADA inhibitory activity and was identified as 5-hydroxy-2-hydroxymethyl-4H-pyran-4-one, based on the results of 1H and 13C NMR spectroscopy. The results of molecular docking suggested that compound 3 binds to the active site and the nonspecific binding site of the ADA. Furthermore, we found that compound 3 is a mixed ADA inhibitor. These results indicate that endophytic strains are a promising source of ADA inhibitors and that compound 3 may be a superior source for use in the preparation of biologically active ADA inhibitor compounds used to treat cancer.


Assuntos
Inibidores de Adenosina Desaminase/química , Ascomicetos/química , Endófitos/química , Plantas Medicinais/microbiologia , Adenosina Desaminase/química , Adenosina Desaminase/metabolismo , Inibidores de Adenosina Desaminase/farmacologia , Ascomicetos/classificação , Ascomicetos/genética , Ascomicetos/isolamento & purificação , Sítios de Ligação , Endófitos/classificação , Endófitos/genética , Endófitos/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Sementes/microbiologia
6.
Comb Chem High Throughput Screen ; 22(2): 113-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30987561

RESUMO

BACKGROUND: Adenosine deaminase (ADA) is an important enzyme in purine metabolism and is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Traditional Chinese Herbal Medicine (TCHM) is widely used alone or in combination with chemotherapy to treat cancer, due to its ability to deliver a broad variety of bioactive secondary metabolites as promising sources of novel organic natural agents. OBJECTIVE: In the present study, 29 varieties of medicinal plants were screened for the presence of ADA inhibitors. RESULTS: Extracts from Reynoutria japonica, Glycyrrhiza uralensis, Lithospermum erythrorhizon, Magnolia officinalis, Gardenia jasminoides, Stephania tetrandra, Commiphora myrrha, Raphanus sativus and Corydalis yanhusuo demonstrated strong ADA inhibition with rates greater than 50%. However, Reynoutria japonica possessed the highest ADA inhibitory activity at 95.26% and so was used in our study for isolating the ADA inhibitor to be further studied. Eight compounds were obtained and their structures were identified. The compound H1 had strong ADA inhibitory activity and was deduced to be emodin by 1H and 13C-NMR spectroscopic analysis with an IC50 of 0.629 mM. The molecular docking data showed that emodin could bind tightly to the active site of ADA. Our results demonstrated that emodin displayed a new biological activity which is ADA inhibitory activity with high cytotoxic activity against K562 leukemia cells. The bioactivity of cordycepin was significantly increased when used in combination with emodin. CONCLUSION: Emodin may represent a good candidate anti-cancer therapy and adenosine protective agent.


Assuntos
Inibidores de Adenosina Desaminase/farmacologia , Antineoplásicos/farmacologia , Emodina/farmacologia , Medicina Tradicional Chinesa , Extratos Vegetais/química , Polygonaceae/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células K562
7.
Burns ; 42(4): 797-806, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27130433

RESUMO

BACKGROUND: To investigate whether pyruvate-enriched oral rehydration solution (Pyr-ORS), compared with citrate-enriched ORS (Cit-ORS), improves hemodynamics and organ function by alleviating vasopermeability and plasma volume loss during intra-gastric fluid rehydration in dogs with severe burn. METHODS: Forty dogs subjected to severe burn were randomly divided into four groups (n=10): two oral rehydrated groups with Pyr-ORS and Cit-ORS (group PR and group CR), respectively, according to the Parkland formula during the first 24h after burns. Other two groups were the intravenous (IV) resuscitation (group VR) with lactated Ringer's solution with the same dosage and no fluid rehydration (group NR). During the next 24h, all groups received the same IV infusion. The hemodynamics, plasma volume, vasopermeability and water contents and function of various organs were determined. Plasma levels of vascular endothelial growth factor (VEGF) and platelet activating factor (PAF) were detected by ELISA. RESULTS: Hemodynamics parameters were significantly improved in group PR superior to group CR after burns. Levels of VEGF and PAF were significantly lower in group PR than in group CR. Organ function parameters were also greatly preserved in group PR, relative to groups CR and NR. Lactic acidosis was fully corrected and survival increased in group PR (50.0%), compared to group CR (20.0%). CONCLUSION: Pyr-ORS was more effective than Cit-ORS in improving hemodynamics, visceral blood perfusion and organ function by alleviating vasopermeability-induced visceral edema and plasma volume loss in dogs with severe burn.


Assuntos
Queimaduras/tratamento farmacológico , Permeabilidade Capilar/efeitos dos fármacos , Hidratação/métodos , Hemodinâmica/efeitos dos fármacos , Ácido Pirúvico/farmacologia , Animais , Bicarbonatos , Queimaduras/mortalidade , Queimaduras/fisiopatologia , Modelos Animais de Doenças , Cães , Fluoresceína-5-Isotiocianato/análise , Glucose , Ácido Láctico/metabolismo , Fator de Ativação de Plaquetas/metabolismo , Cloreto de Potássio , Distribuição Aleatória , Choque/tratamento farmacológico , Cloreto de Sódio , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Am J Emerg Med ; 34(3): 525-30, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26794285

RESUMO

OBJECTIVE: Pyruvate can reduce lipid peroxidation, which plays a critical role in organ injury, in various models. However, it is not fully understood if this inhibition occurs in resuscitation of hemorrhagic shock (HS). This study examines effects of pyruvate Ringer solution (PR) in this respect in rats. METHODS: Rats, subjected to 45% blood loss, were randomly allocated to the 3 groups (n = 18): HS with no fluid resuscitation (group NR), HS resuscitated with lactated Ringer solution (LR) (group LR), and HS resuscitated with PR (group PR). Mean arterial pressure, plasma levels of thiobarbituric acid reactive substances (TBARS), and superoxide dismutase were measured at various time points until 360 minutes after hemorrhage. Visceral organs were harvested at the end for evaluations of the TBARS, antioxidant enzyme, and tissue water content. Other 54 rats with identical procedures without sampling were documented for 24-hour survival rates (n = 18) after fluid resuscitation. RESULTS: Pyruvate Ringer solution significantly increased mean arterial pressure and decreased blood TBARS levels after lethal HS. It also reduced TBARS concentrations and glutathione peroxidase activities but significantly enhanced glutathione reductase activities in most organs and greatly improved the ratios of reduced glutathione over oxidized glutathione in various organs in group PR, compared to group LR. Furthermore, PR significantly improved various organ function and water contents relative to LR. Group PR showed a more than 2-fold higher 24-hour survival rate of group LR. CONCLUSIONS: Pyruvate Ringer solution alleviated organ edema and injury and prompted survival partially through inhibition of lipid peroxidation in various organs in severe HS rats.


Assuntos
Peroxidação de Lipídeos/fisiologia , Insuficiência de Múltiplos Órgãos/terapia , Estresse Oxidativo/efeitos dos fármacos , Ácido Pirúvico/metabolismo , Ressuscitação/métodos , Choque Hemorrágico/terapia , Animais , Soluções Isotônicas/metabolismo , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Ácido Pirúvico/administração & dosagem , Ratos , Ratos Sprague-Dawley , Solução de Ringer , Choque Hemorrágico/complicações , Análise de Sobrevida
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