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1.
Molecules ; 24(20)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31601012

RESUMO

Astragalus radix (radix) have been frequently used for clinical application in China, and the herb residues of radix turn out to be a waste of resources. To escape from this, the medicine value of radix herb residues is mined in this article. We isolated hemicellulose polysaccharide AX-I-3b from radix herb residues by fractional extraction. Monosaccharide-composition analysis revealed that AX-I-3b consisted of arabinose, xylose, and glucose with a molar ratio of 10.4:79.3:1.1. Methylation, NMR and FT-IR analyses showed that AX-I-3b monosaccharide residue was linked as follows: →2,3,4)-ß-d-Xylp-(1→, →4)-ß-d-Arap-(1→, →4)-ß-d-Glcp-(1→. Then, we found that AX-I-3b exhibited antitumor activity against lung cancer in vitro and vivo through MTT assay and xenograft tumor model. Mechanistically, AX-I-3b induced apoptosis in lung cancer cells and xenograft tumors, which is evidenced by the up-regulation of p53, Bax and cleaved caspase-3, and the down-regulation of Bcl-2. Moreover, AX-I-3b synergistically improved the therapeutic ability of cisplatin in xenograft tumors model. Furthermore, AX-I-3b treatment effectively improved the immune organ index, the percentage of spleen lymphocyte subsets and serum cytokine levels in lung cancer mice, supporting that AX-I-3b showed immunomodulatory activity. In conclusion, our results identified AX-I-3b as an antitumor and immunomodulatory agent, providing a new insight into the reutilization of radix herb residue.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Astrágalo (Planta)/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Extratos Vegetais/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Fatores Imunológicos/química , Camundongos , Polissacarídeos/química , Análise Espectral
2.
Fish Shellfish Immunol ; 94: 517-524, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542494

RESUMO

Astragalus polysaccharide (APS) plays important roles in antibacterial, antiviral and antiparasitic activities in mammals, birds and aquatic animals. However, the relationship between non-specific immune responses and intestinal microbiota in sea cucumber (Apostichopus japonicus) after dietary APS supplementation has not been reported to date. Here, the effect of dietary APS supplementation on the non-specific immune response and intestinal microbial composition and species distribution of sea cucumber was explored. We found that although there was no significant effect on sea cucumber growth, the enzymatic activity and expression level of immune- and antioxidant-related genes changed after dietary APS supplementation. Furthermore, the intestinal microbial composition and species distribution of sea cucumber were different at the phylum and genus levels after dietary APS supplementation. The phyla Proteobacteria and Bacteroidetes were significantly different between the APS2 group and CK group. The results of PCA and PCoA analysis also showed that the APS2 group was significantly different compared to the other groups. Finally, analysis of the relationship between non-specific immune responses and the intestinal microbiota showed that the expression level of NF-κB was significantly correlated with intestinal microbiota at the genus level. This finding suggests that dietary APS supplementation might affect the non-specific immune response and intestinal microbiota of sea cucumber through the NF-κB signalling pathway; the appropriate added level was 800 mg/kg. Taken together, our results lay a foundation for further understanding the relationship between non-specific immune responses and intestinal microbial of sea cucumber.


Assuntos
Astrágalo (Planta)/química , Microbioma Gastrointestinal/fisiologia , Imunidade Inata/imunologia , Stichopus/efeitos dos fármacos , Ração Animal/análise , Animais , Dieta , Suplementos Nutricionais/análise , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Stichopus/imunologia , Stichopus/microbiologia
3.
Mol Med Rep ; 20(4): 3701-3708, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485647

RESUMO

Telomere length, a marker of cellular aging, decreases with age and it has been associated with aging­related diseases. Environmental factors, including diet and lifestyle factors, affect the rate of telomere shortening which can be reversed by telomerase. Telomerase activation by natural molecules has been suggested to be an anti­aging modulator that can play a role in the treatment of aging­related diseases. This study aimed to investigate the effect of natural compounds on telomerase activity in human peripheral blood mononuclear cells (PBMCs). The tested compounds included Centella asiatica extract formulation (08AGTLF), Astragalus extract formulation (Nutrient 4), TA­65 (containing Astragalus membranaceus extract), oleanolic acid (OA), maslinic acid (MA), and 3 multi­nutrient formulas (Nutrients 1, 2 and 3) at various concentrations. The mean absorbance values of telomerase activity measured following treatment with some of the above­mentioned formulations were statistically significantly higher compared to those of the untreated cells. In particular, in order of importance with respect to telomerase activation from highest to lowest, 08AGTLF, OA, Nutrient 4, TA­65, MA, Nutrient 3 and Nutrient 2, triggered statistically significant increase in telomerase activity compared to the untreated cells. 08AGTLF reached the highest levels of telomerase activity reported to date, at least to our knowledge, increasing telomerase activity by 8.8 folds compared to untreated cells, while Nutrient 4 and OA were also potent activators (4.3­fold and 5.9­fold increase, respectively). On the whole, this study indicates that the synergistic effect of nutrients and natural compounds can activate telomerase and produce more potent formulations. Human clinical studies using these formulations are required to evaluate their mode of action. This would reveal the health benefits of telomerase activation through natural molecules and would shed new light onto the treatment of aging­related diseases.


Assuntos
Senescência Celular/efeitos dos fármacos , Ativadores de Enzimas/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Extratos Vegetais/farmacologia , Telomerase/metabolismo , Astrágalo (Planta)/química , Células Cultivadas , Descoberta de Drogas , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Ácido Oleanólico/farmacologia , Encurtamento do Telômero/efeitos dos fármacos , Triterpenos/farmacologia
4.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(7): 619-624, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31537247

RESUMO

Objective To investigate the effects of Astragalus polysaccharide (APS) on autophagy and expression of microtubule-associated protein 1 light chain 3B (LC3B), mammalian target of rapamycin (mTOR) and beclin1 in xanthine oxidase (XOD)-induced autophagic model of non-small cell lung cancer A549 cells. Methods A549 cells were divided into five groups: control group, model group, 100, 200 and 400 µg/mL APS-treated group. Except for control group, all groups were administered XOD for 24 hours to establish autophagic models. Morphology of autophagosome was detected by transmission electron microscopy (TEM) and the number was counted by monodansylcadaverine (MDC) staining. The expression levels of LC3B, beclin1 and mTOR were detected by Western blot analysis. Results Compared with the control group, the number of autophagosome in the model group increased; the expression of LC3B and beclin1 significantly increased; while the expression of mTOR significantly decreased. Compared with the model group, the number of autophagosome decreased remarkably; the expression of LC3B and beclin1 severely decreased, and the expression of mTOR obviously increased in 200 or 400 µg/mL APS-treated group. Conclusion APS reduces the level of autophagy, down-regulates the expression of LC3B and beclin1, and increases mTOR expression in the autophagic model of A549 cells induced by XOD.


Assuntos
Astrágalo (Planta)/química , Autofagia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Polissacarídeos/farmacologia , Células A549 , Proteínas Relacionadas à Autofagia , Proteína Beclina-1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Xantina Oxidase
5.
Biomed Pharmacother ; 118: 109180, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302422

RESUMO

BACKGROUND: Astragalus polysaccharide (APS) is a traditional Chinese herbal medicine with anti-inflammatory and anti-aging activities. OBJECTIVE: This study aimed to explore the effect and associated mechanisms of APS on LPS-induced injury in ATDC5 cells, to evaluate the potential of APS for use as an adjuvant therapy for osteoarthritis (OA). MATERIALS AND METHODS: ATDC5 cells were pre-treated with APS and stimulated with lipopolysaccharide (LPS). Cell viability, ROS generation as well as the expression of IL-6, TNF-α, iNOS and Cox-2 were evaluated by performing CCK8 assay, ROS detection, ELISA, western blot and qRT-PCR. The expression of NF-κB and p38MAPK signal pathways related proteins and KLF4 was measured through western blot. RESULTS: LPS increased the expression of IL-6 and TNF-α, elevated the expression of Cox-2, iNOS and increased ROS generation. APS treatment significantly alleviated LPS-induced damage in ATDC5 cells. Besides, miR-92a was down-regulated while KLF4 was up-regulated by APS. At the same time, the targeting relationship between miR-92a and KLF4 was demonstrated. The inhibitory effects of APS on LPS-induced injury in ATDC5 cells were attenuated by the combination of KLF4 siRNA. In addition, LPS induced NF-κB and p38MAPK signal pathways were decreased by APS treatment. Also, the inhibitory effect of APS on NF-κB and p38MAPK signal pathways was reversed by KLF4 siRNA. CONCLUSIONS: The present study reveals that APS protects ATDC5 cells against LPS induced-injury by regulation of miR-92a/KLF4 axis and suppressing NF-κB and p38MAPK signal pathways.


Assuntos
Anti-Inflamatórios/farmacologia , Astrágalo (Planta)/química , Medicamentos de Ervas Chinesas/farmacologia , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/genética , Polissacarídeos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrócitos/imunologia , Condrócitos/metabolismo , Condrócitos/patologia , Regulação para Baixo , Medicamentos de Ervas Chinesas/isolamento & purificação , Expressão Gênica/efeitos dos fármacos , Camundongos , NF-kappa B/antagonistas & inibidores , Osteoartrite , Polissacarídeos/isolamento & purificação , RNA Interferente Pequeno/genética , Regulação para Cima
6.
Zhongguo Zhong Yao Za Zhi ; 44(13): 2736-2741, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31359684

RESUMO

Astragali Radix( AR) polysaccharide for injection( Guoyao Zhunzi Z20040086) is a traditional Chinese medicine for intravenous powder injection developed by Shanxi Academy of Traditional Chinese Medicine in early 1990 s by taking advantage of AR resources in Shanxi province. The effective parts of AR polysaccharides were obtained by advanced technology. The hemogram of patients with radiotherapy and chemotherapy showed alleviations in clinic. However,due to the technical bottleneck in separation of the complex polysaccharides mixture and the difficulties in accurate measurement of the polysaccharide structures,the pharmacodynamic mechanism of the drug remained unclear,and the side effect was hard to control. In recent years,the theoretical studies for polysaccharide receptors have indicated that when polysaccharides bound to protein receptors,only the oligosaccharide fragments of the polysaccharide molecule bound to the receptors,and one or more active sites of oligosaccharide fragments may existed in the polysaccharide molecule.Therefore,the active center of polysaccharides can be studied based on the level of oligosaccharides through degradation of the polysaccharides,which provided a new strategy for breaking through the bottleneck in polysaccharide structure determination. Therefore,this paper reviews the current status of studies for AR polysaccharides for injection,the polysaccharide receptors theory and successful cases,in order to propose the secondary development ideas of AR polysaccharides for injection. The study results will lay a material foundation for the development of new drugs of polysaccharides from traditional Chinese medicine,and provide a basis for the resolution of international difficulties in quality control of polysaccharide drugs and molecular models,so as to further study of glycobiology,and enrich the polysaccharide receptors theory.


Assuntos
Astrágalo (Planta)/química , Medicamentos de Ervas Chinesas , Raízes de Plantas/química , Polissacarídeos/farmacologia , Humanos , Medicina Tradicional Chinesa
7.
Zhongguo Zhong Yao Za Zhi ; 44(13): 2813-2819, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31359695

RESUMO

A rapid and accurate method for determination of astragaloside Ⅳ was established,which was further applied to determine the contents of astragaloside Ⅳ in 87 batches of different origin and different grade of Astragali Radix. The ROC curve was used to analyze the contents of astragaloside Ⅳ in different origin. Simultaneous contents of astragaloside Ⅳ in different grade were compared with chemometrics. HPLC-ELSD method was used to determine the contents of astragaloside Ⅳ. A Vensil MP C18 column( 4. 6 mm×250 mm,5 µm) was used with acetonitrile-water( 32 ∶68) as the mobile phase at a flow rateof 1 m L·min-1. The column temperature was 25 ℃ with ELSD parameters as follows: gas flow rate was 2. 5 L·min-1,the drift tube heating temperature was set to 105 ℃,and the gain value was 4. 0. The optimized method avoided the problem that the consumable quality unstable and the recovery rate was not high. The contents determined by the optimized method were higher than the pharmacopoeia method,with less time and high recovery rate. The ROC curve analysis showed that there was no significant difference of contents of astragaloside Ⅳ between the top grade of Shanxi wild-simulated Astragali Radix top and the first grade of Gansu cultivated Astragali Radix. The contents of astragaloside Ⅳ in the second,third and fourth grade of Shanxi wild-simulated Astragali Radix was significantly higher than those of produced from Gansu.There was a significant negative correlation between the contents of astragaloside Ⅳ and grade in Shanxi Astragali Radix. While there was no correlation for Gansu Astragali Radix. This study provided the basis for the quality grade standard of Astragali Radix.


Assuntos
Astrágalo (Planta)/química , Medicamentos de Ervas Chinesas/análise , Saponinas/análise , Triterpenos/análise , Cromatografia Líquida de Alta Pressão
8.
Microb Pathog ; 135: 103621, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31310831

RESUMO

Astragalus polysaccharides (APS) are a traditional Chinese medicine with a therapeutic effect by enhancing immune function; however, the underlying functional mechanism is still unclear. The aim of the present study was to determine the effect of oral administration of APS on jejunum mucosal immunity in chickens vaccinated against Newcastle disease (ND). One-day-old Hy-Line male chickens were divided into five groups of 20 chicks each: three APS groups, one vaccinated control (VC) group and one non-vaccinated negative control (NC) group. On d 10, the APS groups were orally administered 0.5 mL of APS at doses of 1 mg/mL (APSL), 2 mg/mL (APSM) and 4 mg/mL (APSH) daily for 4 consecutive days. The chicks in the control groups were administered 0.5 mL saline for those 4 days. All groups except NC were administered a ND virus (NDV) vaccine on day 14. The jejunum was removed from 4 randomly selected chickens of each group at 1, 7, 14 and 28 days after vaccination. The jejunal villus height (VH) and crypt depth (CD) were measured and the VH:CD ratio calculated. Immunohistochemistry was used to analyze the differences of IgA+ cells in the jejunum. NDV specific secretory IgA (sIgA) levels in jejunal contents were detected using an indirect ELISA. At most time points, VH:CD ratios, number of IgA+ cells, and sIgA levels were significantly higher in the APS groups than those in VC and NC groups, but there were little differences among the three doses of APS groups. These results indicate that oral administration of APS could enhance the intestinal mucosal immune function of chickens, and APS could be used as a vaccine enhancer.


Assuntos
Astrágalo (Planta)/química , Galinhas/imunologia , Imunidade nas Mucosas/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Doença de Newcastle/imunologia , Polissacarídeos/administração & dosagem , Vacinação/veterinária , Administração Oral , Animais , Modelos Animais de Doenças , Imunoglobulina A Secretora , Jejuno/patologia , Masculino , Medicina Tradicional Chinesa , Vírus da Doença de Newcastle/imunologia , Extratos Vegetais/administração & dosagem
9.
Acta Cir Bras ; 34(5): e201900502, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31166463

RESUMO

PURPOSE: To investigate inhibitory effect of Astragalus polysaccharide (APS) on osteoporosis in ovariectomized rats by regulating FoxO3a/Wnt2 signaling pathway. METHODS: Postmenopausal osteoporosis (PMOP) animal model was developed by excising the bilateral ovaries of rats. The model rats were administered with APS (200 mg/kg, 400 mg/kg, 800 mg/kg) by intragastric administration once daily for 12 weeks. Bone density, bone metabolism index and oxidative stress index were measured in all groups. Furthermore, the regulation of APS of FoxO3a / Wnt2 signaling pathway was observed. RESULTS: APS has an estrogen-like effect, which can increase bone mass, lower serum ALP and BGP values, increase blood calcium content, and increase bone density of the femur and vertebrae in rats. At the same time, APS can increase the bone mineral content of the femur, increase the maximum stress, maximum load and elastic modulus of the ovariectomized rats, improve oxidative stress in rats by increasing the gene expression of ß-catenin and Wnt2 mRNA and inhibiting the gene expression of FoxO3a mRNA. CONCLUSION: Astragalus polysaccharide can effectively alleviate oxidative stress-mediated osteoporosis in ovariectomized rats, which may be related to its regulation of FoxO3a/Wnt2/ß-catenin pathway.


Assuntos
Astrágalo (Planta)/química , Proteína Forkhead Box O3/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Polissacarídeos/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Densidade Óssea/efeitos dos fármacos , Feminino , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Proteína Forkhead Box O3/análise , Expressão Gênica/efeitos dos fármacos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/análise , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/efeitos dos fármacos , Osteoporose/metabolismo , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Reprodutibilidade dos Testes , Resultado do Tratamento , Via de Sinalização Wnt/fisiologia , Proteína Wnt2/análise , Proteína Wnt2/efeitos dos fármacos , beta Catenina/análise , beta Catenina/efeitos dos fármacos
10.
Am J Chin Med ; 47(3): 595-612, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31122040

RESUMO

Although Astragalus polysaccharide (APS) has been shown to have various pharmacological effects, there have been no studies concerning the inhibitory effects of APS on the radiation-induced bystander effects (RIBE). The aim of this study was to investigate whether APS could suppress RIBE damage by inhibiting cell growth, micronucleus (MN) formation and 53BP1 foci number increased in bone marrow mesenchymal stem cells (BMSCs), named bystander cells, as well as to explore its mechanism. In this study, APS decreased proliferation and colony rate of bystander cells by inducing cell cycle arrest at G1 phase via extrinsic and intrinsic DNA damage. Regarding mechanism, APS inhibited mitogen-activated protein kinase (MAPK) signal pathway by down-regulating the expression of the key proteins, phosphorylated JNK (p-JNK), phosphorylated ERK (p-ERK) but not phosphorylated P38 (p-P38), and down-regulating their downstream function protein and molecule, cyclooxygenase-2 (COX-2) and reactive oxygen species (ROS). Moreover, in bystander cells, APS inhibits expression of transforming growth factor ß receptor II (TGF- ß R II), a cell membrane receptor, resulting in lower ROS production and secretion via TGF- ß R-JNK/ERK-COX-2/ROS not P38 signaling. They gave a hint that the decreased RIBE damage induced by APS treatment involved TGF- ß R-JNK/ERK-COX-2/ROS down-regulation.


Assuntos
Astrágalo (Planta)/química , Efeito Espectador/efeitos dos fármacos , Carbono , Proliferação de Células/efeitos dos fármacos , Fase G1/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos da radiação , Polissacarídeos/farmacologia , Células Cultivadas , Ciclo-Oxigenase 2 , Dano ao DNA , Humanos , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta/metabolismo
11.
Molecules ; 24(9)2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31058835

RESUMO

In several European countries, especially in Sweden, the seeds of the species Astragalus boeticus L. were widely used as coffee substitutes during the 19th century. Nonetheless, data regarding the phytochemistry and the pharmacological properties of this species are currently extremely limited. Conversely, other species belonging to the Astragalus genus have already been extensively investigated, as they were used for millennia for treating various diseases, including cancer. The current work was addressed to characterize cycloartane glycosides from A. boeticus, and to evaluate their cytotoxicity towards human colorectal cancer (CRC) cell lines. The isolation of the metabolites was performed by using different chromatographic techniques, while their chemical structures were elucidated by nuclear magnetic resonance (NMR) (1D and 2D techniques) and electrospray-ionization quadrupole time-of-flight (ESI-QTOF) mass spectrometry. The cytotoxic assessment was performed in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays in Caco-2, HT-29 and HCT-116 CRC cells. As a result, the targeted phytochemical study of A. boeticus enabled the isolation of three new cycloartane glycosides, 6-O-acetyl-3-O-(4-O-malonyl)-ß-d-xylopyranosylcycloastragenol (1), 3-O-(4-O-malonyl)-ß-d-xylopyranosylcycloastragenol (2), 6-O-acetyl-25-O-ß-d-glucopyranosyl-3-O-ß-d-xylopyranosylcycloastragenol (3) along with two known compounds, 6-O-acetyl-3-O-ß-d-xylopyranosylcycloastragenol (4) and 3-O-ß-d-xylopyranosylcycloastragenol (5). Importantly, this work demonstrated that the acetylated cycloartane glycosides 1 and 4 might preferentially inhibit cell growth in the CRC cell model resistant to epidermal growth factor receptor (EGFR) inhibitors.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Astrágalo (Planta)/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glicosídeos/farmacologia , Triterpenos/química , Acilação , Antineoplásicos Fitogênicos/química , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glicosídeos/química , Células HCT116 , Células HT29 , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Espectrometria de Massas por Ionização por Electrospray , Suécia
12.
Food Chem Toxicol ; 130: 317-325, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31128217

RESUMO

Triterpenoids are well known modulators of metabolic syndrome. One of the suggested modes of action (MoAs) involves peroxisome proliferator-activated receptor gamma (PPARγ) binding. In this study we aimed to: (i) evaluate in silico potential metabolites and PPARγ-mediated MoA of the sapogenin of the main saponin present in a purified saponins' mixture (PSM) from Astragalus glycyphylloides; (ii) estimate in silico and in vivo PSM's toxicity; and (iii) investigate in vivo antihyperglycaemic, hypolipidaemic, antioxidant and hepatoprotective effects of PSM. Metabolites and toxicity were predicted using Meteor and Derek Nexus expert systems (Lhasa Limited) and PPARγ binding was investigated using the software MOE (CCG Inc.). PSM's acute oral toxicity was evaluated in mice and the pharmacological effects were assessed in streptozotocin-induced diabetic spontaneously hypertensive rats (SHRs). Liver histopathology was studied as well. PPARγ weak partial agonism was predicted in silico for 24 probable/plausible Phase I metabolites which docking poses were clustered in 12 different binding modes with characteristic protein-ligand interactions. PSM's beneficial effects on the levels of blood glucose, triglycerides, and total cholesterol, on oxidative stress markers and liver histology in diabetic SHRs were comparable to those of the PPARγ ligand pioglitazone. PSM's safety profile was confirmed in silico and in vivo.


Assuntos
Astrágalo (Planta)/química , Síndrome Metabólica/tratamento farmacológico , Saponinas/química , Saponinas/farmacologia , Animais , Sítios de Ligação , Pressão Sanguínea/efeitos dos fármacos , Simulação por Computador , Diabetes Mellitus Experimental/tratamento farmacológico , Descoberta de Drogas , Feminino , Masculino , Camundongos , Estrutura Molecular , Estresse Oxidativo , PPAR gama/agonistas , Ligação Proteica , Conformação Proteica , Ratos , Ratos Endogâmicos SHR , Saponinas/toxicidade
13.
Molecules ; 24(10)2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31137782

RESUMO

Macrophages occur in polarized phenotypes, whose characteristics determine the role they play in tumor growth. The M1 phenotype macrophages promote tumoricidal responses and suppress tumor growth. Our previous study showed that a polysaccharide isolated from Radix Astragali, named RAP, was itself non-cytotoxic but induced RAW264.7 cells' cytotoxicity against cancer cells. The current study was undertaken to determine its mechanism. Series studies was conducted to show that RAP is able to induce much higher gene expression of M1 markers, including iNOS, IL-6, TNF-a, and CXCL10, compared with the control group. When RAP-induced BMDMs were transplanted together with 4T1 tumor cells in BALB/c mice, both tumor volume and tumor weight decreased. Further studies indicated that RAP induces the Notch signaling pathway in RAW264.7 cells. The function of Notch signaling in macrophage polarization was confirmed by using γ-secretase inhibitor. These results suggested that Astragalus polysaccharide RAP induces macrophage's polarization to M1 phenotype via the Notch signaling pathway.


Assuntos
Astrágalo (Planta)/química , Polaridade Celular , Macrófagos/citologia , Macrófagos/metabolismo , Polissacarídeos/farmacologia , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Polaridade Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Fenótipo , Células RAW 264.7 , Carga Tumoral/efeitos dos fármacos
14.
Biomed Pharmacother ; 115: 108927, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31071509

RESUMO

BACKGROUND/AIMS: Astragalus polysaccharide (APS) has been clarified to possess antibacterial, antiviral and other activities. MicroRNA-152 (miR-152) is a tumor suppressor, which has been testified to be involved in promoting osteogenic differentiation of marrow mesenchymal stem cells (MSCs). However, whether APS can affect BMSCs proliferation and osteogenic differentiation via mediating miR-152 remains uninvestigated. METHODS: After treatment with APS or transfection with pre-miR-152 and anti-miR-152, cell viability, cell proliferation-associated factors, differentiation of BMSCs-related genes, and the relative miR-152 expression was determined by CCK-8, Western blot and qRT-PCR assays. The relationship between miR-152 and BMP9 was assessed by qRT-PCR and dual luciferase activity assay. The effects of BMP9 on cell proliferation and osteogenic differentiation were determined in BMSCs after transfection with pEX-BMP9 and sh-BMP9. The key components in PI3K/AKT and Wnt/ß-catenin pathways were analyzed by Western blot. RESULTS: APS promoted proliferation and differentiation of BMSCs by increasing viable cells, up-regulating CyclinD1, down-regulating p21, and increasing expressions of Runx2, OCN, OPN, and Col-1. miR-152 was down-regulated by APS and miR-152 suppression exhibited the similar promoting effects on BMSCs, whereas miR-152 overexpression inhibited proliferation and differentiation of BMSCs. BMP9 was a direct target of miR-152 and was involved in mediating the function of miR-152 in BMSCs. BMP9 up-regulation enhanced proliferation and differentiation of BMSCs. BMP9 was observed to activate PI3K/AKT and Wnt/ß-catenin pathways in BMSCs. CONCLUSION: These results demonstrated that APS promoted proliferation and osteogenic differentiation of BMSCs by down-regulating miR-152 and further up-regulating BMP9 and activating PI3K/AKT and Wnt/ß-catenin pathways.


Assuntos
Astrágalo (Planta)/química , Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , MicroRNAs/genética , Osteogênese/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Diferenciação Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Regulação para Baixo , Masculino , Osteogênese/genética , Polissacarídeos/isolamento & purificação , Ratos Sprague-Dawley
15.
Zhongguo Zhong Yao Za Zhi ; 44(7): 1410-1415, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31090299

RESUMO

This research aims to develop an UHPLC method, based on core-shell column(i.e. superficially porous particles), for simultaneous determination of eight isoflavonoids including formononetin,(6αR,11αR)-3-hydroxy-9,10-dimethoxypterocarpan, calycosin-7-O-ß-D-glucopyranoside,(3R)-7,2-dihydroxy-3,4-dimethoxyisoflavone, calycosin, ononin,(6αR,11αR)-9,10-dimethoxypterocarpan-3-O-ß-D-glucopyranoside, and(3R)-7,2-dihydroxy-3,4-dimethoxyisoflavan-7-O-ß-D-glucopyranoside in Astragali Radix. The analysis was performed on an Agilent Poroshell EC-C_(18 )column(2.1 mm×100 mm, 2.7 µm) with 0.2% formic acid solution(A)-acetonitrile(B) as mobile phase for gradient elution. The flow rate was 0.5 mL·min~(-1), with column temperature of 40 ℃ and the wavelengths were set at 260 and 280 nm. According to the results, all calibration curves showed good linearity(R~2>0.999 8) within the tested concentration ranges. Both the intra-and inter-day precisions for 8 isoflavonoids were less than 0.80%, with the mean recovery at the range of 94.71%-104.6%. Thus, the newly developed UHPLC method using core-shell column owned the advantages in terms of rapid analysis, low column pressure and less solvent consumption, thus enabling the usage of conventional HPLC systems. Meanwhile, quantitative evaluation was carried out for 22 batches of commercial Astragali Radix. It has been found that great variations occurred for the content of the individual isoflavonoids among different batches; in contrast, the total content of total 8 isoflavonoids(>0.1%) was stable in most samples, indicating that it was reasonable to involve all isoflavonoids as the chemical markers for the quality control of Astragali Radix.


Assuntos
Astrágalo (Planta)/química , Medicamentos de Ervas Chinesas/normas , Flavonas/análise , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos/análise , Raízes de Plantas/química , Controle de Qualidade
16.
Arch Environ Contam Toxicol ; 77(3): 344-358, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31020373

RESUMO

Honeybees, due to their wide-ranging foraging behaviour, have great potentials for monitoring environmental quality. Therefore, the purpose of this study was to use honeybees as bioindicators for the detection of toxic and essential metals (Cd, Cr, Cu, and Fe) in the environment. Totally, 180 soil, plant (including root and aerial part), honeybees, and honey samples were collected from 12 sites within the main beekeeping and honey production regions in Markazi Province, Iran in 2016. After acid digestion of samples, the metal concentrations were measured by inductively coupled plasma-optical emission spectrometers. The translocation factor (TF), and bioconcentration factor (BCF) of metals were computed. The results showed that among the analyzed bee samples, Cd (mg kg-1) was detected in amounts ranging from 0.01 to 2.35, Cr (mg kg-1) ranged from 0.02 to 18.10, Cu (mg kg-1) ranged from 2.00 to 39.11, and Fe (mg kg-1) ranged from 163 to 1695. BCF and TF values obtained showed that the Astragalus gossypinus would have a great accumulation ability for Cd and Cr. The results indicated that honeybees could be used to detect the spatial patterns of metal contaminations in the environment they dwell in.


Assuntos
Abelhas , Monitoramento Ambiental/métodos , Mel/análise , Metais/análise , Poluentes do Solo/análise , Animais , Astrágalo (Planta)/química , Abelhas/química , Biomarcadores Ambientais , Flores/química , Irã (Geográfico) , Raízes de Plantas/química , Plantas/química
17.
Molecules ; 24(7)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30978905

RESUMO

Astragalus is a very interesting plant genus, well-known for its content of flavonoids, triterpenes and polysaccharides. Its secondary metabolites are described as biologically active compounds showing several activities, e.g., immunomodulating, antibacterial, antiviral and hepatoprotective. This inspired us to analyze the Bulgarian endemic A. aitosensis (Ivanisch.) to obtain deeper information about its phenolic components. We used extensive chromatographic separation of A. aitosensis extract to obtain seven phenolic compounds (1-7), which were identified using combined LC-MS and NMR spectral studies. The 1D and 2D NMR analyses and HR-MS allowed us to resolve the structures of known compounds 5-7 as isorhamnetin-3-O-robinobioside, isorhamnetin-3-O-(2,6-di-O-α-rhamno-pyranosyl-ß-galactopyranoside), and alangiflavoside, respectively, and further comparison of these spectral data with available literature helped us with structural analysis of newly described flavonoid glycosides 1-4. These were described in plant source for the first time.


Assuntos
Astrágalo (Planta)/química , Flavonoides/química , Glicosídeos/química , Fenóis/química , Cromatografia Líquida , Flavonoides/isolamento & purificação , Glicosídeos/classificação , Glicosídeos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Fenóis/isolamento & purificação , Triterpenos/química
18.
Environ Sci Pollut Res Int ; 26(16): 16409-16421, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30982193

RESUMO

Dissolved organic matter (DOM) can become a carrier of soil contaminants. Therefore, an understanding of the evolution and characteristics of DOM produced by Chinese milk vetch during green manuring is crucial. In this study, DOM solutions from 28 days' manuring with three different organic materials were characterized using three-dimensional fluorescence excitation-emission matrix (3D-EEM) with parallel factor (PARAFAC) analysis, and ultraviolet-visible spectroscopy. With the green manuring milk vetch at flowering period (MVFP), the DOC and water-soluble cadmium (WS-Cd) in soil solution reached 1875 mg/l and 2.64 µg/l, respectively, on day 6 after manuring. The PARAFAC analysis modeled three components: protein-like (tryptophan) and two humic-like components (humic acid and fulvic acid); DOM produced by MVFP was primarily protein-like during the early stage of decomposition. The aromaticity and molecular weight of DOM in the MVFP treatment was lower than in the other treatments, which could promote the release of soil particle-adsorbed Cd to soil solution. Principal components analysis showed that aromaticity was the main factor affecting Cd solubility, and the negative linear correlation of aromaticity with WS-Cd reached 0.4827. The results of this study supported the idea that manuring with MVFP might accelerate Cd infiltration to deep soil with water under gravity.


Assuntos
Astrágalo (Planta)/química , Cádmio/análise , Compostagem/métodos , Poluentes do Solo/análise , Adsorção , Cádmio/química , Análise Fatorial , Substâncias Húmicas/análise , Análise de Componente Principal , Solo/química , Poluentes do Solo/química , Espectrometria de Fluorescência/métodos , Espectrofotometria Ultravioleta , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química
19.
J Coll Physicians Surg Pak ; 29(4): 392-394, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30925971

RESUMO

The aim of this study was to determine the effect of Astragalus polysaccharide (APS) on the expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in mice with Lewis transplantable lung cancer. It was an experimental study carried out from June 2017 to January 2018 at the College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China. Forty male SPF-level C57BL/6J mice were selected and inoculated with Lewis lung cancer cell suspension in the right axilla of the mice to establish a lung-cancer mouse model. The mice were randomly divided into a model control group and APS groups with high, middle and low dosages, respectively, 10 in each group. After inoculation of Lewis tumor cell suspension for 2 days, mice in the model control group were injected intraperitoneally with 50 mL/kg of 0.9% sodium chloride solution, whereas, mice in the APS groups with high, middle and low dosages were intraperitoneally injected with APS at 100, 50, 25 mg/kg, respectively. The research results showed that APS can effectively inhibit the growth and metastasis of Lewis lung cancer in mice, improve immune organ function, inhibit the protein expression of VEGF and EGFR in tumor tissues, and have a concentration-effect relationships.


Assuntos
Astrágalo (Planta)/química , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Receptores ErbB/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/farmacologia , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Animais , Receptores ErbB/metabolismo , Injeções Intraperitoneais , Masculino , Camundongos , Distribuição Aleatória , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Res Vet Sci ; 124: 137-148, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30901666

RESUMO

The present study evaluated the toxic effects of Tilmicosin (TIL) on adult rats. The rats received a single subcutaneous injection of TIL at different doses (10, 25, 50, 75 and 100 mg/kg bw). TIL altered the biochemical parameters including liver and kidney function markers, glucose level and lipid profile as well as resulted in histopathological lesions in liver and adrenal glands mostly in rats exposed to 75 and 100 mg/kg bw. Then the role of Astragalus polysaccharide (APS) at 100 and 200 mg/kg bw, in modulating the toxic effects induced by high dose of TIL was evaluated. Single injection of TIL at a dose of 75 mg/kg bw was found to increase the activity of ALT, AST and ALP enzymes, induce the generation of reactive oxygen species (ROS) and decrease the total antioxidant capacity (TAC). TIL upregulated the hepatic mRNA expression of heat shock protein 70 (HSP70) and nuclear factor kappa B (NF-kB) while blocked the Nrf2/HO-1 mediated response. These changes were also associated with increasing tumer necrosis factor-alpha (TNF-α), interlukin1-beta (IL-1ß) and nitric oxide levels. On the other hand, the results indicate that APS has a beneficial role particularly at high level in alleviating the stress and the hepatotoxic effects elicited by TIL injection in rats.


Assuntos
Antibacterianos/toxicidade , Astrágalo (Planta)/química , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Tilosina/análogos & derivados , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/fisiopatologia , Animais , Análise Química do Sangue , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Testes Hematológicos , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Tilosina/toxicidade
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