RESUMO
Renal tubular ectopic lipid deposition (ELD) plays a significant role in the development of chronic kidney disease, posing a great threat to human health. The present work aimed to explore the intervention effect and potential molecular mechanism of a purified tea polysaccharide (TPS3A) on renal tubular ELD. The results demonstrated that TPS3A effectively improved kidney function and slowed the progression of tubulointerstitial fibrosis in high-fat-diet (HFD)-exposed ApoE-/- mice. Additionally, TPS3A notably suppressed lipogenesis and enhanced lipolysis, as shown by the downregulation of lipogenesis markers (SREBP-1 and FAS) and the upregulation of lipolysis markers (HSL and ATGL), thereby reducing renal tubular ELD in HFD-fed ApoE-/- mice and palmitic-acid-stimulated HK-2 cells. The AMPK-SIRT1-FoxO1 axis is a core signal pathway in regulating lipid deposition. Consistently, TPS3A significantly increased the levels of phosphorylated-AMPK, SIRT1, and deacetylation of Ac-FoxO1. However, these effects of TPS3A on lipogenesis and lipolysis were abolished by AMPK siRNA, SIRT1 siRNA, and FoxO1 inhibitor, resulting in exacerbated lipid deposition. Taken together, TPS3A shows promise in ameliorating renal tubular ELD by inhibiting lipogenesis and promoting lipolysis through the AMPK-SIRT1-FoxO1 signaling pathway.
Assuntos
Dieta Hiperlipídica , Lipogênese , Lipólise , Camundongos Endogâmicos C57BL , Polissacarídeos , Animais , Lipogênese/efeitos dos fármacos , Camundongos , Lipólise/efeitos dos fármacos , Masculino , Dieta Hiperlipídica/efeitos adversos , Humanos , Polissacarídeos/farmacologia , Polissacarídeos/administração & dosagem , Sirtuína 1/metabolismo , Sirtuína 1/genética , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Túbulos Renais/metabolismo , Túbulos Renais/efeitos dos fármacos , Camellia sinensis/química , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Chá/química , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genéticaRESUMO
The Ca2+-calpain signaling plays a pivotal role in regulating the upstream signaling pathway of cellular autophagy. The aim of the current work was to investigate the role of Ca2+-calpain signaling in the regulation of macrophage autophagy by a Laminaria japonica polysaccharide (LJP61A) in Ox-LDL induced macrophages and high fat diet fed atherosclerotic mice. Results revealed that the LJP61A markedly decreased the levels of intracellular Ca2+, calpain1, calpain2 and their downstream effectors (Gsα, cAMP and IP3), and simultaneously enhanced autophagy activity and lipid metabolism, thereby reducing lipid accumulation in the Ox-LDL stimulated macrophages and lipid-laden plaques in atherosclerotic mice. Moreover, BAPTA-AM (a Ca2+ chelator) and calpeptin (a calpain inhibitor) synergistically strengthened the beneficial effects of LJP61A on autophagy and lipid metabolism by decreasing the levels of intracellular Ca2+, calpain1, calpain2, and their downstream effectors (Gsα, cAMP and IP3) induced by Ox-LDL. These findings suggested that the LJP61A suppressed macrophage derived foam cell formation and atherosclerosis by modulating the Ca2+-calpain-mediated autophagy.
Assuntos
Aterosclerose , Laminaria , Animais , Camundongos , Células Espumosas , Laminaria/metabolismo , Calpaína/metabolismo , Calpaína/farmacologia , Macrófagos , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Lipoproteínas LDL/metabolismo , Transdução de Sinais , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , AutofagiaRESUMO
Osteocalcin was reported to regulate muscle energy metabolism, thus fighting fatigue during exercise. The current work aimed to investigate the anti-fatigue effect and the underlying mechanism of a homogeneous polysaccharide (PCPY-1) from Polgonatum cyrtonema after structure characterization. In the exhaustive swimming mouse model and the co-culture system of BMSCs/C2C12 cells, PCPY-1 significantly stimulated BMSC differentiation into osteoblasts as determined by ALP activity, matrix mineralization, and the protein expressions of osteogenic markers BMP-2, phosphor-Smad1, RUNX2, and osteocalcin. Meanwhile, PCPY-1 remarkably enhanced myoblast energy metabolism by upregulating osteocalcin release and GPRC6A protein expression; the phosphorylation levels of CREB and HSL; the mRNA levels of GLUT4, CD36, FATP1, and CPT1B; and ATP production in vitro and in vivo. Accordingly, PCPY-1 exhibited good anti-fatigue capacity in mice as confirmed by fatigue-related indicators. Our findings indicated PCPY-1 could enhance osteocalcin-mediated communication between bones and muscles, which was conducive to muscle energy metabolism and ATP generation, thus alleviating fatigue in exhausted swimming mice.
Assuntos
Polygonatum , Camundongos , Animais , Osteocalcina/genética , Osteocalcina/metabolismo , Diferenciação Celular , Osteoblastos , Músculos/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Trifosfato de Adenosina/metabolismo , Receptores Acoplados a Proteínas G/genéticaRESUMO
Promoting M1 polarization of tumor-associated macrophages (TAMs) is an effective pathway for malignant tumor therapy. In this study, we aimed to demonstrate whether homogeneous Dendrobium officinale polysaccharide (DOP) could promote M1 polarization of TAMs to inhibit tumor growth, and how it promoted. Results exhibited that DOP could inhibit the tumor growth and promote the M1 polarization of TAMs in tumor-bearing mice. Macrophage depletion and replenishment experiment clearly proved that the inhibitory effect of DOP on tumor growth is dependent on promoting M1 polarization of TAMs. Moreover, we found that DOP could reach tumor microenvironment (TME) and directly bind to TAMs to promote its M1 polarization via targeting toll-like receptor 2 (TLR2) after oral administration. These results clarified that DOP could remarkably inhibit the tumor growth of tumor-bearing mice via directly targeting the TLR2 of TAMs to promote its M1 polarization.
Assuntos
Dendrobium , Neoplasias , Animais , Camundongos , Neoplasias/patologia , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Receptor 2 Toll-Like , Microambiente Tumoral , Macrófagos Associados a TumorRESUMO
BACKGROUND: Parkinson's disease (PD) is an age-related neurodegenerative disorder without effective treatments. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been suggested to be capable of protecting against PD by inhibiting endoplasmic reticulum (ER) stress-mediated neuronal apoptosis. PURPOSE: This study was aimed to evaluate the antiparkinsonian effect of dendrobine and reveal its underlying mechanisms from the perspective of MANF-mediated ER stress suppression. METHODS: Behavioral assessments of PD mice as well as LDH/CCK-8 assay in SH-SY5Y cells and primary midbrain neurons were carried out to detect the antiparkinsonian effect of dendrobine. Immunofluorescence, western blot, flow cytometry and shRNA-mediated MANF knockdown were used to determine the apoptosis of dopaminergic neurons and the expressions of ER stress-related proteins for investigating the underlying mechanism of dendrobine. RESULTS: Dendrobine significantly ameliorated the motor performance of PD mice and attenuated the injuries of dopaminergic neurons. Dendrobine could also relieve neuronal apoptosis, up-regulate MANF expression and inhibit ER stress, which were largely abolished by shRNA-mediated MANF knockdown in PD model. CONCLUSION: Dendrobine might protect against PD by inhibiting dopaminergic neuron apoptosis, which was achieved by facilitating MANF-mediated ER stress suppression. Our study suggested that dendrobine could act as a MANF up-regulator to protect against PD, and provided a potential candidate for exploring etiological agents of PD.
Assuntos
Alcaloides , Neurônios Dopaminérgicos , Estresse do Retículo Endoplasmático , Doença de Parkinson , Alcaloides/farmacologia , Animais , Antiparkinsonianos/farmacologia , Apoptose/efeitos dos fármacos , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Camundongos , Fatores de Crescimento Neural/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , RNA Interferente Pequeno/farmacologiaRESUMO
The present work aimed to explore the effect and underlying mechanism of a homogeneous Laminaria japonica polysaccharide (LJP61A) on macrophage polarization in high-fat-diet-fed LDLr-/- mice and Ox-LDL-induced macrophages. Results showed that LJP61A remarkably reduced the lesion burden in atherosclerotic mice, alleviated lipid deposition in Ox-LDL-stimulated macrophages, decreased the expression of M1 macrophage markers, and increased the expression of M2 macrophage markers, thus reducing the M1/M2 macrophage phenotype ratio. Meanwhile, the autophagic flux of macrophages was enhanced by LJP61A treatment in vitro and in vivo. 3-Methyladenine is an autophagic inhibitor. As expected, this inhibitor blocked the effects of LJP61A on macrophage polarization. SIRT1 and FoxO1 are two key upstream genes that control the autophagy behavior. We also found that LJP61A significantly up-regulated the expression of SIRT1 and FoxO1. However, these effects of LJP61A were abolished by the SIRT1 siRNA and FoxO1 inhibitor AS1842856. These results suggested that LJP61A reduced atherosclerosis in HFD-induced LDLr-/- mice via regulating autophagy-mediated macrophage polarization.
Assuntos
Aterosclerose , Laminaria , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Aterosclerose/metabolismo , Autofagia , Macrófagos , Camundongos , Polissacarídeos/metabolismo , Polissacarídeos/farmacologiaRESUMO
The present study aimed at assuring whether homogeneous cultivated Dendrobium huoshanense stem polysaccharide (cDHPS) could inhibit gastric cancer in vivo, and whether its anti-gastric cancer activity could be affected by its molecular weight and O-acetyl group. Three different fractions (cDHPS-I, cDHPS-II and cDHPS-III) with decreased molecular weights and one fraction (cDHPS-IV) without O-acetyl group were prepared from cDHPS. Their structures were identified systematically. The backbone of cDHPS-I-III was the same as that of cDHPS, while their relative molecular weights displayed a decreasing order as follows: cDHPS > cDHPS-I > cDHPS-II > cDHPS-III. The backbone of cDHPS-IV was similar to those of cDHPS and cDHPS-I-III, but with the absence of O-acetyl groups. Animal experiments exhibited that cDHPS and cDHPS-I-IV could significantly inhibit tumor growth, induce tumor cell apoptosis, suppress tumor angiogenesis and enhance T cell immune response of murine forestomach carcinoma (MFC) tumor-bearing mice. Moreover, all the above effects of cDHPS and cDHPS-I-IV on MFC tumor-bearing mice exhibited a decreasing order as follows: cDHPS > cDHPS-I > cDHPS-II > cDHPS-III > cDHPS-IV. The results suggest that cDHPS could inhibit gastric cancer in vivo, and its anti-gastric cancer activity was closely linked with its molecular weight and O-acetyl group.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Dendrobium/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Polissacarídeos/farmacologia , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Estrutura Molecular , Peso Molecular , Extratos Vegetais/química , Polissacarídeos/química , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Some bioactive ingredients in foods are unstable and easily degraded during processing, storage, transportation and digestion. To enhance the stability and bioavailability, some food hydrogels have been developed to encapsulate these unstable compounds. In this paper, the preparation methods, formation mechanisms, physicochemical and functional properties of some protein hydrogels, polysaccharide hydrogels and protein-polysaccharide composite hydrogels were comprehensively summarized. Since the hydrogels have the ability to control the release and enhance the bioavailability of bioactive ingredients, the encapsulation and release mechanisms of polyphenols, flavonoids, carotenoids, vitamins and probiotics by hydrogels were further discussed. This review will provide a comprehensive reference for the deep application of polysaccharide/protein hydrogels in food industry.
Assuntos
Hidrogéis , Polissacarídeos , Disponibilidade Biológica , Carboidratos da Dieta , ProteínasRESUMO
Oleogels were prepared by emulsion template method through 3.0% tea polyphenol ester (Tp-ester) particles with four fatty acid chain length (Tp-laurate [C12], Tp-myristate [C14], Tp-palmitate [C16], and Tp-stearate [C18]) and 2.5% citrus pectin, and then were used in cookie production as fat replacer. Effects of the fatty acid chain length on the hydrophilicity/hydrophobicity of Tp-ester, on the appearance, microstructure, and firmness of dried products, on rheological features of oleogels, on the dynamic viscoelasticity and textural characteristics of cookies dough, and on cookies qualities were revealed. With the increase in the fatty acid chain length, the θo and θw values of four Tp-esters increased, the firmness of dried products with smaller oil droplets got larger, and the gel intensity of oleogels increased, but the quality scores, spread ratio, and break strength of the cookies did not change significantly. With the increase in the replacement levels of butter with oleogels, the harder cookie dough with weaker gel strength and the softer cookies with lower hedonic scores and crispness were found. At 25% and 50% replacement levels, cookies prepared with oleogels using Tp-palmitate or Tp-stearate particles exhibited similar hedonic scores, break strength, spread ratio, and storage stabilities to that of butter cookies. PRACTICAL APPLICATION: Cookies are relished by all age groups due to their taste and crispness, but include high content of saturated fatty acids that are harmful to people's health. The result of this study will help the industry to better design cookies through oleogels with tea polyphenols ester and pectin, and will provide healthy cookies with little or no butter for consumers.
Assuntos
Ésteres/química , Ácidos Graxos/química , Óleos de Plantas/química , Polifenóis/química , Manteiga/análise , Camellia/química , Emulsões/química , Farinha/análise , Manipulação de Alimentos , Dureza , Humanos , Compostos Orgânicos/química , Reologia , Triticum/química , ViscosidadeRESUMO
Three bibenzyls 1-3 and six other compounds 4-9 were firstly isolated from Dendrobium huoshanense stems. They were identified as 3',4-dihydroxy-3,5'-dimethoxybibenzyl(1), batatasin â ¢(2), 3,4'-dihydroxy-5-methoxy bibenzyl(3), dihydroconiferyl dihydro-p-coumarate(4), syringaresinol(5), 3-(4-hydroxyphenyl)-propionic acid ethyl ester(6),(3-ethylphenyl)-1,2-ethanediol(7),(S)-5-hydroxy-3,4-dimethyl-5-pentylfuran-2(5H)-one(8) and loliolide(9). Anti-inflammation assay showed that bibenzyls 1-3 could significantly inhibit the production of nitric oxide(NO) and the expression of tumor necrosis factor α(TNF-α) and interleukin 1ß(IL-1ß) mRNA in LPS-induced RAW264.7 macrophages. Mechanism study exhibited that the phosphorylation of nuclear factor kappa B(NF-κB) p65, inhibitor of κB(IκB), extracellular regulatedprotein kinase(ERK), c-Jun N-terminalkinase(JNK), p38 and Akt of LPS-induced RAW264.7 macrophages could be remarkably reduced by 1. These results suggested that the inflammatory response of LPS-induced RAW264.7 macrophages could be significantly inhibited by 1-3. Additionally, the anti-inflammatory effect of 1 might be contributed to its ability on the regulation of NF-κB, MAPKs and Akt signaling pathways.
Assuntos
Dendrobium , Anti-Inflamatórios/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Lipopolissacarídeos , Macrófagos , NF-kappa B , Óxido Nítrico , Óxido Nítrico Sintase Tipo IIRESUMO
Glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L-cells is a pleiotropic hormone with beneficial potential related to islet function, diet control, glucose homeostasis, inflammation relief, and cardiovascular protection. The present study aimed at investigating the effect of Polygonatum cyrtonema polysaccharide (PCP) after structural identification on GLP-1 secretion and the possible mechanism involved in the PCP-stimulated secretion of GLP-1. It was found that GLP-1 secretion was effectively promoted (p < 0.01) by PCP both in rats with oral administration for 5 weeks (13.9 ± 0.3-35.8 ± 0.3 pmol/L) and ileal administration within 2 h (13.6 ± 0.4-34.1 ± 1.1 pmol/L) and in enteroendocrine NCI-H716 cells with direct stimulation within 24 h (2.05 ± 0.3-20.7 ± 0.2 pmol/L). The sweet taste receptor T1R2/T1R3 was identified to be essential for NCI-H716 cells to directly recognize PCP. The intervention experiments showed that PCP-stimulated GLP-1 secretion was significantly depressed (p < 0.01) not only by antibodies, siRNA, and the inhibitor of T1R2/T1R3 but also by an adenylate cyclase inhibitor. These results suggest that PCP stimulates GLP-1 secretion from enteroendocrine cells possibly through activation of the T1R2/T1R3-mediated cAMP signaling pathway.
Assuntos
AMP Cíclico/metabolismo , Células Enteroendócrinas/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Extratos Vegetais/farmacologia , Polygonatum/química , Polissacarídeos/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Células Enteroendócrinas/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
The present work aims to investigate the effects and underlying mechanism of a homogeneous Laminaria japonica polysaccharide (LJP61A) on acute kidney injury (AKI) in mice. According to the results of biochemical and pathological analysis, we concluded that LJP61A could protect kidney from the damage of adriamycin in AKI mice. Compared to the model group, the mRNA level of cytokines (TNF-α, IL-1ß and MCP-1) and protein level of mesenchymal markers demsin were decrease by the treatment of LJP61A while the protein levels of podocyte structure markers (Nephrin and WT-1) were increased. Moreover, the adriamycin-induced enhancement of phosphor-p65, phosphor-p38, phosphor-ERK1/2 and phosphor-JNK in the kidney of AKI mice were significantly suppressed by LJP61A. Similar variation was observed in the mRNA and protein levels of TGF-ß1 and Smad3. These results suggested that LJP61A prevented acute kidney injury possibly via regulating TGF-ß1-mediated Smad3, MAPKs and NF-κB signaling pathways.
Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Antibióticos Antineoplásicos/efeitos adversos , Doxorrubicina/efeitos adversos , Laminaria/química , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Biomarcadores , Biópsia , Citocinas/metabolismo , Modelos Animais de Doenças , Imuno-Histoquímica , Mediadores da Inflamação , Testes de Função Renal , Masculino , Camundongos , Estrutura Molecular , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificaçãoRESUMO
The stems of Dendrobium huoshanense have long been used to prevent various diseases, including inflammatory diseases. This study was aimed to explain the anti-inflammatory effect of D. huoshanense stems in LPS-induced RAW 264.7 macrophages and to discover potential anti-inflammatory compounds. Results exhibited that D. huoshanense stems ethanol extract could significantly inhibit LPS-induced production of NO, TNF-α and IL-1ß. Based on bioassay guided strategy, four bibenzyls (1-4) were isolated from D. huoshanense stems for the first time. Anti-inflammatory assay showed 1-4 could remarkably inhibit the production of NO in LPS-induced macrophages. Moreover, quantitative RT-PCR analysis displayed that the mRNA levels of iNOs, TNF-α and IL-1ß could also be significantly reduced by 1-4. These results suggested that D. huoshanense stems ethanol extract and bibenzyls 1-4 might be well developed as therapeutic agent to prevent inflammatory diseases.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Bibenzilas/isolamento & purificação , Dendrobium/química , Macrófagos/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Bibenzilas/farmacologia , Bioensaio/métodos , Etanol , Interleucina-1beta/genética , Lipopolissacarídeos , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células RAW 264.7/citologia , RNA Mensageiro/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genéticaRESUMO
The structure features and anti-gastric cancer activities in vitro of stem, root, leaf and flower polysaccharides from cultivated Dendrobium huoshanense were investigated systematically. Stem polysaccharide (cDHPS) was composed of â4)-ß-D-Glcp-(1â, â4)-ß-D-Manp-(1â, â4)-3-O-acetyl-ß-D-Manp-(1â with the molecular weight of 2.59 × 105 Da; root polysaccharide (cDHPR) was composed of â3,5)-α-L-Araf-(1â, â4)-ß-D-Glcp-(1â, â4)-ß-D-Manp-(1â, â4,6)-ß-D-Manp-(1â, â6)-α-D-Galp-(1â and terminal ß-L-Araf with the molecular weight of 1.41 × 104 Da; leaf polysaccharide (cDHPL) was composed of â4)-ß-D-Glcp-(1â, â4)-ß-D-Manp-(1â, â4)-3-O-acetyl-ß-D-Manp-(1â, â3,6)-ß-D-Manp-(1â and terminal α-D-Galp with the molecular weight of 2.09 × 105 Da; and flower polysaccharide (cDHPF) was composed of â4)-ß-D-Glcp-(1â, â4)-ß-D-Manp-(1â, â3,6)-ß-D-Manp-(1â and terminal α-D-Galp with the molecular weight of 4.78 × 105 Da. Among these four polysaccharides, cDHPS showed the best anti-gastric cancer activity evidenced by the inhibited growth and c-myc expression as well as the enhanced apoptosis and p53 expression of murine forestomach carcinoma (MFC) cells, suggesting their difference in anti-gastric cancer activity should be contributed to their difference in structure features.
Assuntos
Dendrobium/química , Flores/química , Folhas de Planta/química , Raízes de Plantas/química , Caules de Planta/química , Polissacarídeos/química , Polissacarídeos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos , Conformação Molecular , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
A homogenous polysaccharide (GXG) from Dendrobium huoshanense with stable digestive behavior and effective immunoregulatory function was employed to explore its underlying molecular basis regulating intestinal mucosal immune response from the view of interaction between GXG and intestinal epithelial cells (IECs). Using in vitro established co-culture system consisting of IECs and lamina propria cells (LPCs), we found the immune response of LPCs could be effectively regulated by GXG-stimulated IECs, and three cytokines including IL-6, MCP-1 and CINC-1 produced from GXG-stimulated IECs were the main factors involved in modulating immune response of LPCs. Toll-like receptor 4 (TLR4) was identified as an essential receptor for IECs to directly bind GXG. Receptor intervention experiments demonstrated that TLR4 mediated GXG-induced activation of IECs, which further induces immunomodulating effects on LPCs. These results suggest that GXG could modulate the immune response in LPCs by the direct interaction with IECs via TLR4.
Assuntos
Células Epiteliais/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Polissacarídeos/farmacologia , Receptor 4 Toll-Like/metabolismo , Animais , Linhagem Celular , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Dendrobium/química , Fatores Imunológicos/metabolismo , Linfócitos/efeitos dos fármacos , Masculino , Polissacarídeos/metabolismo , Ratos Sprague-DawleyRESUMO
In the present study, the hypoglycemic mechanism of a homogeneous Dendrobium huoshanense polysaccharide (GXG) was investigated using type 2 diabetic (T2D) mouse model. With a 5-week oral administration of GXG, the levels of fasting blood glucose, glycosylated serum protein and serum insulin in T2D mice were decreased, and the glucose tolerance and the insulin sensitivity were improved. The histological analysis, the periodic acid-schiff staining and the immunofluorescence staining of insulin, glucagon and apoptosis showed that the hypoglycemic effect of GXG was related to the improvement of pancreatic ß-cell quantity and function and the regulation of hepatic glucose metabolism. Western blot analysis indicated that the up-regulated IRS1-PI3K-Akt phosphorylation followed by the down-regulated FoxO1/GSK 3ß phosphorylation contributed to the enhanced glycogen synthesis and the decreased gluconeogenesis by GXG, suggesting that the response of insulin-mediated IRS1-PI3K-Akt-FoxO1/GSK 3ß signaling to GXG might be the required mechanism for GXG-ameliorated development of type 2 diabetes.
Assuntos
Dendrobium , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Glucanos/farmacologia , Glucose/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Fígado/efeitos dos fármacos , Animais , Proteína Forkhead Box O1/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Homeostase/efeitos dos fármacos , Proteínas Substratos do Receptor de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
The present work investigated the inhibitory activity of the polysaccharide from cultivated Dendrobium huoshanense (cDHP) on lung inflammation in cigarette smoke (CS)-induced mouse model. cDHP was mainly composed of mannose and glucose in a molar ratio of 1.89: 1.00, and had a backbone with linkages of 1,4-Manp, 1,4-Glcp, 1,4,6-Manp and 1-Glcp. Hematoxylin and Eosin (HE) staining and immunohistochemistry analysis showed that cDHP can increase alveolar number, thicken alveolar wall, inhibit pulmonary bulla formation and decrease inflammatory cell infiltration as compared to the model group. ELISA determination revealed that cDHP can inhibit CS-induced enhancement in TNF-α and IL-1ß secretion in serum and lung. These results suggested that cDHP can resist CS-induced lung inflammation. Further, the phosphorylation analysis of p65, IκB, p38 and JNK as well as the DNA binding activity analysis of NF-κB and AP-1 implied that the anti-inflammation function of cDHP is mediated via regulating NF-κB and MAPK signaling.
Assuntos
Dendrobium/química , Pneumonia/tratamento farmacológico , Polissacarídeos/uso terapêutico , Animais , Fumar Cigarros/efeitos adversos , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Interleucina-1beta/metabolismo , Camundongos , Polissacarídeos/química , Fator de Necrose Tumoral alfa/metabolismoRESUMO
In this work, a purified Laminaria japonica polysaccharide (LJP61A) was chemically modified to obtain three sulfated polysaccharides (SLJP1, SLJP2 and SLJP3) with different degrees of sulfation using the method of chlorosulfonic acid/pyridine. The effects and underlying mechanism of SLJP1, SLJP2 and SLJP3 on the suppression of macrophage foam cell formation were further investigated using the model of oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation. Results exhibited that the macrophage foam cell formation induced by ox-LDL could be significantly alleviated by these sulfated polysaccharides in a dose-dependent manner. Meanwhile, the enhancement of PPAR-γ mRNA expression in ox-LDL induced macrophages was remarkably inhibited by these sulfated polysaccharides. Moreover, the cellular inflammation induced by ox-LDL could also be remarkably mitigated by these sulfated polysaccharides. These results indicated that the sulfated L. japonica polysaccharides could inhibit the conversion of macrophage into foam cell via obstructing PPAR-γ activation and alleviating cellular inflammation.
Assuntos
Células Espumosas/efeitos dos fármacos , Inflamação/tratamento farmacológico , Laminaria/química , Polissacarídeos/química , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Lipoproteínas LDL/genética , Macrófagos/efeitos dos fármacos , Camundongos , PPAR gama/química , PPAR gama/genética , Polissacarídeos/farmacologia , Células RAW 264.7/efeitos dos fármacos , Sulfatos/químicaRESUMO
BACKGROUND: We hypothesized that a high ticagrelor loading dose (LD) may improve platelet inhibition in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). METHODS: This interventional multicentre open-label trial randomized 278 patients with NSTE-ACS to a high (360 mg) or conventional (180 mg) ticagrelor LD. The primary outcome was the platelet reactivity index (PRI) 1 hour after administration of the LD. Secondary outcomes included PRI at 0.5 hour, 1 hour, 8 hours, and 24 hours; periprocedural myocardial infarction (PMI); major cardiac adverse events; and bleeding events. RESULTS: Two hundred sixty-two patients completed the major end points. PRI was lower in the high-LD group than in the conventional-LD group at any time point (all, P < 0.05), including at 1 hour (12.2% vs 16.7%; P = 0.023). At 0.5 hour, the high-LD group showed a lower high-platelet reactivity rate (49.6% vs 60.2%; P = 0.013) and a higher low-platelet reactivity rate (24.8% vs 12.8%; P = 0.017) than did the conventional LD group. No significant differences in the bleeding rates were found between the 2 groups (14% vs 14.3%). Four cases of PMI and 1 death in each group, as well as 1 acute myocardial infarction in the conventional LD group, occurred. There was no stroke, target lesion revascularization, or target vessel revascularization. CONCLUSIONS: Doubling the ticagrelor LD achieved faster onset and greater platelet inhibition without an increase in adverse events in patients with NSTE-ACS undergoing PCI.