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1.
Bioorg Chem ; 147: 107369, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38640721

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a complex pathogenic metabolic syndrome characterized by increased inflammation and endoplasmic reticulum stress. In recent years, natural polysaccharides derived from traditional Chinese medicine have shown significant anti-inflammatory effects, making them an attractive therapeutic option. However, little research has been conducted on the therapeutic potential of dried tangerine peel polysaccharide (DTPP) - one of the most important medicinal resources in China. The results of the present study showed that DTPP substantially reduced macrophage infiltration in vivo and suppressed the expression of pro-inflammatory factors and endoplasmic reticulum stress-related genes. Additionally, surface plasmon resonance analysis revealed that DTPP had a specific affinity to myeloid differentiation factor 2, which consequently suppressed lipopolysaccharide-induced inflammation via interaction with the toll-like receptor 4 signaling pathway. This study provides a potential molecular mechanism underlying the anti-inflammatory effects of DTPP on NAFLD and suggests DTPP as a promising therapeutic strategy for NAFLD treatment.


Assuntos
Estresse do Retículo Endoplasmático , Inflamação , Polissacarídeos , Receptor 4 Toll-Like , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/antagonistas & inibidores , Polissacarídeos/farmacologia , Polissacarídeos/química , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Camundongos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Antígeno 96 de Linfócito/antagonistas & inibidores , Antígeno 96 de Linfócito/metabolismo , Carthamus tinctorius/química , Camundongos Endogâmicos C57BL , Estrutura Molecular , Relação Dose-Resposta a Droga , Relação Estrutura-Atividade , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química
2.
Acta Biochim Biophys Sin (Shanghai) ; 56(4): 621-633, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38516704

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with a global prevalence of 25%. Patients with NAFLD are more likely to suffer from advanced liver disease, cardiovascular disease, or type II diabetes. However, unfortunately, there is still a shortage of FDA-approved therapeutic agents for NAFLD. Lian-Mei-Yin (LMY) is a traditional Chinese medicine formula used for decades to treat liver disorders. It has recently been applied to type II diabetes which is closely related to insulin resistance. Given that NAFLD is another disease involved in insulin resistance, we hypothesize that LMY might be a promising formula for NAFLD therapy. Herein, we verify that the LMY formula effectively reduces hepatic steatosis in diet-induced zebrafish and NAFLD model mice in a time- and dose-dependent manner. Mechanistically, LMY suppresses Yap1-mediated Foxm1 activation, which is crucial for the occurrence and development of NAFLD. Consequently, lipogenesis is ameliorated by LMY administration. In summary, the LMY formula alleviates diet-induced NAFLD in zebrafish and mice by inhibiting Yap1/Foxm1 signaling-mediated NAFLD pathology.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Lipogênese , Peixe-Zebra , Diabetes Mellitus Tipo 2/metabolismo , Fígado/metabolismo , Dieta Hiperlipídica , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Lipídeos , Camundongos Endogâmicos C57BL , Proteína Forkhead Box M1/metabolismo
3.
Carbohydr Polym ; 169: 304-314, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28504149

RESUMO

We report here the discovery of a polysaccharide, namely EUP1, with anti-inflammatory activity from the herb of Eucommia ulmoides Oliv. We separated three polysaccharide fractions from this herb based on acidity and screened them for their activity in modulating the phenotype of murine macrophages. Among them, EUP1 was the only fraction to exert such a function - it stimulated Raw 264.7 cells to express CD206 and a key anti-inflammatory cytokine interleukin-10. Having fully characterised EUP1 with a series of chromatographic and spectroscopic analyses, we evaluated its anti-inflammatory effects in both in vitro and in vivo inflammatory models. In the murine model of sepsis induced by lipopolysaccharide, administration of EUP1 effectively suppressed the expression of major inflammatory cytokines, alleviated lung injury and increased animal survival rate. In summary, EUP1, with a clearly elucidated chemical structure and solid anti-inflammatory activity, may become a valuable candidate for further development into an anti-septic therapeutic agent.


Assuntos
Anti-Inflamatórios/farmacologia , Eucommiaceae/química , Polissacarídeos/farmacologia , Sepse/tratamento farmacológico , Animais , Lipopolissacarídeos , Camundongos , Extratos Vegetais/química , Células RAW 264.7
4.
Dalton Trans ; 43(4): 1854-61, 2014 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-24257441

RESUMO

The use of selenium for anticancer therapy has been heavily explored during the last decade. Amino acids (AAs) play central roles both as building blocks of proteins and intermediates in metabolism. In the present study, AAs-modified selenium nanoparticles (SeNPs@AAs) have been successfully synthesized in a simple redox system. Typical neutral (valine), acidic (aspartic acid) and basic (lysine) amino acids were used to decorate SeNPs, and the stable and homodisperse nanoparticles were characterized by zeta potential and transmission electron microscope. The result of X-ray photoelectron spectra (XPS) showed that the interaction of -NH3(+) groups of the amino acids with negative-charged SeNPs could be a driving force for dispersion of the nanoparticles. The screening of in vitro anticancer activities demonstrated that SeNPs@AAs exhibited differential growth inhibitory effects on various human cancer cell lines. Among them, SeNPs decorated by Lys displayed higher anticancer efficacy than those of valine and aspartic acid. The studies on the in vitro cellular uptake mechanisms revealed that SeNPs@AAs were internalized by cancer cells through endocytosis. Flow cytometric analysis and the determination of caspase activity indicated that treatment of the MCF-7 breast adenocarcinoma cells with SeNPs@AAs led to a dose-dependent increase in apoptosis. Moreover, it was found that SeNPs@AAs-induced ROS overproduction could be the upstream signal of caspase activation and mitochondrial dysfunction in cancer cells. Taken together, our results suggest that these amino acid biocompatible nanoparticles might have potential application as chemopreventive and chemotherapeutic agents for human cancers.


Assuntos
Aminoácidos/química , Antineoplásicos/farmacologia , Nanopartículas Metálicas/química , Selênio/química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular Tumoral , Ativação Enzimática , Humanos , Microscopia Eletrônica de Varredura , Mitocôndrias/efeitos dos fármacos , Neoplasias/patologia , Espécies Reativas de Oxigênio/metabolismo
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