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1.
Acta Pharmacol Sin ; 42(9): 1507-1515, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33311599

RESUMO

Astroglioma is the most common primary tumor in the central nervous system without effective treatment strategies. Temozolomide (TMZ) is a chemotherapeutic drug to treat astroglioma but exhibits low potency and has side effects. Therefore, there is an urgent need to develop new compounds to treat astroglioma. Dalbergia sissoo Roxb was the source of Dalbergia odorifera in traditional Chinese medicine (TCM) and has been clinically used as an anti-tumor medicine. 4-Methoxydalbergione (4MOD) is purified from Dalbergia sissoo Roxb., and shows an inhibitory effect on osteosarcoma, but its effects on astroglioma have not been reported. Here, we evaluate its anti-astroglioma effects on both in vitro and in vivo models. In cultured astroglioma U87 cells, 4MOD inhibited cell proliferation and induced cell apoptosis in a time- and concentration-dependent manner. Compared with TMZ, 4MOD exhibited a tenfold greater potency of anti-astroglioma effects. 4MOD effectively stalled the cell cycle in G2 phase. Transcriptome sequencing (RNA-seq) showed that 4MOD upregulated 158 genes and downregulated 204 genes that are mainly enriched in cell membrane, cell division, cell cycle, p53, TNF, and MAPK signaling pathways, which may underlie its anti-tumor mechanisms. In a nude mouse xenograft model transplanted with U87 cells, 10 mg/kg 4MOD slowed down tumor growth rate, while at 30 mg/kg dose, it reduced tumor size. Collectively, this study demonstrates that 4MOD is a potent native compound that remarkably inhibits U87 astroglioma growth in both in vitro and in vivo models.


Assuntos
Astrocitoma/tratamento farmacológico , Astrocitoma/metabolismo , Benzoquinonas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Astrocitoma/genética , Astrocitoma/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dalbergia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Expressão Gênica , Xenoenxertos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus
2.
J Agric Food Chem ; 68(5): 1186-1197, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31855431

RESUMO

A bioactive polysaccharide from microalga Chlorella pyrenoidosa (CPP) was successively prepared via DEAE-52 and G-100 columns. Nuclear magnetic resonance analysis showed that the main glycosidic bonds were composed of 1,2-linked-α-l-Fucp, 1,4-linked-α-l-Rhap, 1,4-linked-ß-l-Araf, 1-linked-α-d-Glcp, 1,3-linked-ß-d-GlcpA, 1,4-linked-ß-d-Xylp, and 1,3,6-linked-ß-d-Manp. Its molecular weight was 5.63 × 106 Da. The hypolipidemic effect and intestinal flora regulation of CPP on diet-induced rats were evaluated through histopathology and biochemistry analyses. CPP could improve plasma and liver lipid metabolism and accelerate the metabolism of the cecal total bile acids and short-chain fatty acids. CPP has also upregulated the adenosine-monophosphate-activated protein kinase α and downregulated the acetyl-CoA carboxylase, sterol regulatory element-binding protein 1c, and ß-hydroxy ß-methylglutaryl-CoA expressions. Moreover, with the 16S rRNA gene sequencing, it was revealed that the composition of intestinal flora changed drastically after treatment, such as the bloom of Coprococcus_1, Lactobacillus, and Turicibacter, whereas there was a strong reduction of the [Ruminococcus]_gauvreauii_group. The above results illustrated that CPP might be served as an effective ingredient to ameliorate lipid metabolism disorders and intestinal flora in hyperlipidemia rats.


Assuntos
Chlorella/química , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperlipidemias/tratamento farmacológico , Microalgas/química , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Humanos , Hiperlipidemias/metabolismo , Hiperlipidemias/microbiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Extratos Vegetais/química , Polissacarídeos/química , Ratos , Ratos Wistar
3.
Viruses ; 11(11)2019 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-31717616

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) is a huge threat to the modern pig industry, and current vaccine prevention strategies could not provide full protection against it. Therefore, exploring new anti-PRRSV strategies is urgently needed. Ginsenoside Rg1, derived from ginseng and notoginseng, is shown to exert anti-inflammatory, neuronal apoptosis-suppressing and anti-oxidant effects. Here we demonstrate Rg1-inhibited PRRSV infection both in Marc-145 cells and porcine alveolar macrophages (PAMs) in a dose-dependent manner. Rg1 treatment affected multiple steps of the PRRSV lifecycle, including virus attachment, replication and release at concentrations of 10 or 50 µM. Meanwhile, Rg1 exhibited broad inhibitory activities against Type 2 PRRSV, including highly pathogenic PRRSV (HP-PRRSV) XH-GD and JXA1, NADC-30-like strain HNLY and classical strain VR2332. Mechanistically, Rg1 reduced mRNA levels of the pro-inflammatory cytokines, including IL-1ß, IL-8, IL-6 and TNF-α, and decreased NF-κB signaling activation triggered by PRRSV infection. Furthermore, 4-week old piglets intramuscularly treated with Rg1 after being challenged with the HP-PRRSV JXA1 strain display moderate lung injury, decreased viral load in serum and tissues, and an improved survival rate. Collectively, our study provides research basis and supportive clinical data for using Ginsenoside Rg1 in PRRSV therapies in swine.


Assuntos
Ginsenosídeos/farmacologia , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico , Vírus da Síndrome Respiratória e Reprodutiva Suína/efeitos dos fármacos , Animais , Antivirais/farmacologia , Linhagem Celular , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Macrófagos Alveolares/virologia , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/metabolismo , Síndrome Respiratória e Reprodutiva Suína/patologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Vírus da Síndrome Respiratória e Reprodutiva Suína/patogenicidade , Transdução de Sinais/efeitos dos fármacos , Suínos , Doenças dos Suínos/tratamento farmacológico , Doenças dos Suínos/imunologia , Doenças dos Suínos/patologia , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
4.
Foods ; 8(9)2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31500248

RESUMO

Many delicious and nutritional macrofungi are widely distributed and used in East Asian regions, considered as edible and medicinal foods. In this study, 11 species of dried and fresh, edible and medicinal macrofungi, Ganoderma amboinense, Agaricus subrufescens, Dictyophora indusiata, Pleurotus sajor-caju, Pleurotus ostreatus, Pleurotus geesteranu, Hericium erinaceus, Stropharia rugosoannulata, Pleurotus sapidus, Antrodia camphorata, and Lentinus edodes (Berk.) Sing, were investigated to determine the content of their nutritional components, including proteins, fat, carbohydrates, trace minerals, coarse cellulose, vitamins, and amino acids. The amino acid patterns and similarity of macrofungi were distinguished through principal component analysis and hierarchical cluster analyses, respectively. A total of 103 metabolic small molecules of macrofungi were identified by nuclear magnetic resonance spectroscopy and were aggregated by heatmap. Moreover, the macrofungi were classified by principal component analysis based on these metabolites. The results show that carbohydrates and proteins are two main components, as well as the nutritional ingredients, that differ among various species and varied between fresh and dried macrofungi. The amino acid patterns in L. edodes and A. subrufescens were different compared with that of the other tested mushrooms.

5.
Food Chem Toxicol ; 128: 233-239, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30995513

RESUMO

The contributions to hypoglycemic function and gut microbiota regulation by water and ethanol extracts of the microalgae Chlorella pyrenoidosa and Spirulina platensis were determined. An ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis indicated that most of the compounds in the 55% ethanol extracts of C. pyrenoidosa (CP55) and S. platensis (SP55) were polyunsaturated fatty acids. After an 8-week high-fat high-sucrose diet with C. pyrenoidosa and S. platensis supplementation, glucose tolerance was improved, and the composition of the gut microbiota was altered. The diversity of the gut bacterial community was evaluated using 16S rRNA gene pyrosequencing. C. pyrenoidosa supplementation increased the abundance of Ruminococcus, Parasutterella, and Erysipelotrichacea and decreased the abundance of Lactobacillus, Turicibacter, and Blautia; S. platensis supplementation increased the abundance of Oscillibacter, Parasutterella, and Alloprevotella and decreased the abundance of Turicibacter. Moreover, Erysipelotrichacea and Ruminococcus were uniquely increased in C. pyrenoidosa treatment groups. Thus, CP55 and SP55 may be developed as effective natural food materials for preventing diabetes, and Ruminococcus may play a vital role in the treatment of diabetes.


Assuntos
Chlorella/química , Ácidos Graxos Insaturados/análise , Hipoglicemiantes/farmacologia , Spirulina/química , Animais , Cromatografia Líquida de Alta Pressão/métodos , Microbioma Gastrointestinal/genética , Teste de Tolerância a Glucose , Masculino , Espectrometria de Massas/métodos , RNA Ribossômico 16S/genética , Ratos , Especificidade da Espécie
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