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1.
Mar Drugs ; 17(10)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31601041

RESUMO

Since our last review in 2015, the study and use of fucoidan has extended in several research areas. Clinical use of fucoidan for the treatment of renal disease has become available and human safety studies have been undertaken on radiolabeled fucoidan for the purpose of imaging thrombi. Fucoidan has been incorporated into an increasing number of commercially available supplements and topical treatments. In addition, new measuring techniques are now available to assess the biologically relevant uptake of fucoidans and to assist in production. Microbiome modulation and anti-pathogenic effects are increasingly promising applications for fucoidans, due to the need for alternative approaches to antibiotic use in the food chain. This review outlines promising new developments in fucoidan research, including potential future therapeutic use.


Assuntos
Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Animais , Suplementos Nutricionais , Humanos
2.
Chin J Nat Med ; 17(9): 641-649, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31526499

RESUMO

Bupleurum polysaccharides (BPs) is isolated from Bupleurum smithii var. parvifolium, a key traditional Chinese medicine. The study was to investigate the effects of BPs on diabetic kidney injury. After two intraperitoneal injections of streptozotozin (STZ) 100 mg·kg-1, renal injury in diabetic mice was induced and BPs was orally administrated at dosages of 30 and 60 mg·kg-1·d-1. The STZ injected mice developed renal function damage, renal inflammation and fibrosis known as diabetic kidney disease (DKD). BPs significantly reduced serum creatinine level and urinary albumin excretion rate, with the attenuated swelling of kidneys. BPs treatment obviously alleviated the pathological damage of renal tissue. The progression of renal injury in BPs treated mice was inhibited with less expression of type IV collagen (Col IV), fibronectin (FN) and α-smooth muscle actin (α-SMA). The inhibition of inflammation in kidney was associated with the reduced level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). BPs administration suppressed the over-expression of toll like receptor 4 (TLR4) and high-mobility group box 1 (HMGB1) with lowered activity of nuclear factor kappa B (NF-κB) in renal tissue of diabetic mice. Oral administration of BPs effectively prevented the development ofrenal injury in diabetic mice. This study suggested that the protection provided by BPs might affect through the interruption of HMGB1-TLR4 pathway, leading to the inhibition of renal inflammation and fibrotic process.


Assuntos
Bupleurum/química , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Proteína HMGB1/metabolismo , Polissacarídeos/uso terapêutico , Receptor 4 Toll-Like/metabolismo , Animais , Citocinas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/metabolismo , Inflamação/prevenção & controle , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos Endogâmicos C57BL , Raízes de Plantas/química , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/toxicidade , Fator de Transcrição RelA/metabolismo
3.
Carbohydr Polym ; 225: 115210, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521316

RESUMO

Macromolecular drugs, such as proteins and peptides, are lately readily available and used in the treatment of diseases including diabetes and cancer, as well as in therapies such as gene therapy, wound dressing, and tissue engineering. However, the bioavailability, the extent and the rate at which these drugs reach the target tissue are highly dependent on the carrier and on the route of administration. Among the multitude of biocompatible polymers used to design vehicles for macromolecular drugs, polysaccharides are preferred due to their mucoadhesive, antimicrobial, and anti-inflammatory properties. This review aims to give an overview on the evolution of polysaccharide-based vehicles recommended in the controlled delivery of proteins and peptides, mainly reported in the last five years. Both physically and chemically cross-linked drug delivery systems are presented such as: porous hydrogels, polyelectrolyte complexes and layer-by-layer thin films. Even if the pharmaceutical formulations for oral administration of proteins and peptides are preferred, other friendly routes are discussed in this review, such as transdermal delivery.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Hidrogéis , Peptídeos/farmacocinética , Polímeros , Polissacarídeos , Proteínas/farmacocinética , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/uso terapêutico , Disponibilidade Biológica , Diabetes Mellitus/tratamento farmacológico , Humanos , Hidrogéis/química , Hidrogéis/uso terapêutico , Substâncias Macromoleculares/farmacocinética , Neoplasias/tratamento farmacológico , Polímeros/química , Polímeros/uso terapêutico , Polissacarídeos/química , Polissacarídeos/uso terapêutico , Engenharia Tecidual
4.
Mar Drugs ; 17(9)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527536

RESUMO

Fucoidan extracts may have beneficial effects in age-related macular degeneration(AMD). Over-the-counter fucoidan preparations are generally undefined, crude extracts. In thisstudy, we investigated the effect of a crude fucoidan extract from Fucus distichus subspeciesevanescens (Fe) on the retinal pigment epithelium (RPE). Fe extract was investigated for chemicalcomposition and molar mass. It was tested in primary RPE and RPE cell line ARPE19. Oxidativestress was induced with tert-butyl hydroperoxide, cell viability evaluated with MTT assay, VEGFsecretion assessed in ELISA. Phagocytosis was evaluated in a fluorescence microscopic assay.Wound healing ability was tested in a scratch assay. Additionally, the inhibition of elastase andcomplement system by Fe extract was studied. The Fe extract contained about 61.9% fucose andhigh amounts of uronic acids (26.2%). The sulfate content was not as high as expected (6.9%). It wasnot toxic and not protective against oxidative stress. However, Fe extract was able to reduce VEGFsecretion in ARPE19. Phagocytosis was also reduced. Concerning wound healing, a delay could beobserved in higher concentrations. While some beneficial effects could be found, it seems tointerfere with RPE function, which may reduce its beneficial effects in AMD treatment.


Assuntos
Fucus/química , Degeneração Macular/tratamento farmacológico , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular , Avaliação Pré-Clínica de Medicamentos , Humanos , Degeneração Macular/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Cultura Primária de Células , Epitélio Pigmentado da Retina/metabolismo , Suínos , Testes de Toxicidade , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/efeitos dos fármacos
5.
Carbohydr Polym ; 224: 115195, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472848

RESUMO

Brown seaweeds are well-known source of bioactive compounds, which are producing a variety of secondary metabolites with promising bioactive properties. Traditionally, seaweeds used as ingredients in medicine for many centuries in Asian countries. However, the protective mechanisms of many metabolites found in seaweeds are remains to be determined. Thus, applications of seaweeds are limited because of poor understanding of their structural features and mechanisms responsible for their bioactive properties. In the present study, anti-inflammatory properties of fucoidan isolated from the brown seaweed Padina commersonii (PCF) was evaluated against LPS-activated RAW 264.7 macrophages. PCF was characterized using NMR, FT-IR, and HPAE-PAD spectrum (for mono sugar composition). It was observed that PCF is rich in fucose and sulfate as well as a similar structure to the commercial fucoidan. Western blots and RT-qPCR analysis were used to determine the protective effects of PCF after LPS challenge using RAW 264.7 macrophages. According to the results, PCF significantly down-regulated LPS-activated mRNA and protein expression levels of TLR2, TLR4, and MyD88 which are known inducers/activators of NF-κB transcriptional factors. The results, obtained from this study demonstrated PCF has a potential to inhibit LPS-induced inflammatory responses via blocking TLR/MyD88/ NF-κB signal transduction.


Assuntos
Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , NF-kappa B/metabolismo , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptores Toll-Like/metabolismo , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Citosol/efeitos dos fármacos , Citosol/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/metabolismo , Camundongos , Monossacarídeos/análise , Fator 88 de Diferenciação Mieloide/metabolismo , Óxido Nítrico/metabolismo , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Células RAW 264.7 , RNA Mensageiro/genética
6.
Chin J Nat Med ; 17(8): 600-607, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472897

RESUMO

To recognize the potential medicinal value of the Dendrobium sonia, polysaccharide (DSP) was extracted, purified, and investigated for its immunomodulatory activity. In vitro, DSP was shown to enhance the viability (MTT assay) and phagocytosis of macrophages. In cyclophosphamide-induced immunosuppressed mice, DSP increased serum levels of TNF-α, IL-6 and IFN-γ (enzyme-linked immunosorbent assay, ELISA), and ameliorated the imbalance of the community of gut microbiota as detected by 16S ribosomal RNA gene sequencing. These results suggest that DSP might be beneficial for patients under immunosuppressed conditions.


Assuntos
Dendrobium/química , Disbiose/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hospedeiro Imunocomprometido , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Animais , Ciclofosfamida/toxicidade , Citocinas/sangue , Disbiose/induzido quimicamente , Disbiose/imunologia , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Monossacarídeos/química , Fagocitose/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Células RAW 264.7
7.
Nanoscale ; 11(32): 15173-15183, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31380881

RESUMO

Chemotherapy, the most commonly applied cancer treatment, often causes unexpected failure due to multidrug resistance (MDR). To overcome MDR, we have designed a platform to realize a combinational synergistic effect of a natural bioactive product (fucoidan), anticancer small compound (doxorubicin), and photothermal nanocarrier (Pt nanoparticle) to treat drug-resistant breast cancer cells. Especially, fucoidan, a sulfated, polysaccharide-structured, therapeutic biopolymer, has been recently recognized as a potential anticancer compound; however, its cancer-inhibiting efficacy has been regarded as low owing to its insufficient level in serum following its conventional oral ingestion. To enhance its potency, fucoidan was applied as a biocompatible surfactant and surface-coating biopolymer in nanocarrier synthesis to manufacture coral-like, fucoidan-coated Pt nanoparticles with a rough surface morphology by a one-pot method. As a result, the biological-thermo-chemo trimodal combination treatment showed excellent therapeutic efficiency against the MDR breast cancer cell MCF-7 ADR both in vitro and in vivo, and the computed tomography contrast effect was also confirmed from the constituent element Pt. Beyond universal application in drug delivery and photothermal therapy, the present approach of applying a MDR modulating/anticancer natural product from nanoparticle synthesis to theranostics will contribute greatly to maximizing their potential through interdisciplinary convergence in the near future.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nanopartículas Metálicas/química , Platina/química , Polissacarídeos/química , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Sinergismo Farmacológico , Feminino , Hemólise/efeitos dos fármacos , Humanos , Células MCF-7 , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Fototerapia , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Tomografia Computadorizada por Raios X
8.
Molecules ; 24(15)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374852

RESUMO

Galactosaminoglycans (GalAGs) are sulfated glycans composed of alternating N-acetylgalactosamine and uronic acid units. Uronic acid epimerization, sulfation patterns and fucosylation are modifications observed on these molecules. GalAGs have been extensively studied and exploited because of their multiple biomedical functions. Chondroitin sulfates (CSs), the main representative family of GalAGs, have been used in alternative therapy of joint pain/inflammation and osteoarthritis. The relatively novel fucosylated chondroitin sulfate (FCS), commonly found in sea cucumbers, has been screened in multiple systems in addition to its widely studied anticoagulant action. Biomedical properties of GalAGs are directly dependent on the sugar composition, presence or lack of fucose branches, as well as sulfation patterns. Although research interest in GalAGs has increased considerably over the three last decades, perhaps motivated by the parallel progress of glycomics, serious questions concerning the effectiveness and potential side effects of GalAGs have recently been raised. Doubts have centered particularly on the beneficial functions of CS-based therapeutic supplements and the potential harmful effects of FCS as similarly observed for oversulfated chondroitin sulfate, as a contaminant of heparin. Unexpected components were also detected in CS-based pharmaceutical preparations. This review therefore aims to offer a discussion on (1) the current and potential therapeutic applications of GalAGs, including those of unique features extracted from marine sources, and (2) the potential drawbacks of this class of molecules when applied to medicine.


Assuntos
Acetilgalactosamina/uso terapêutico , Artralgia/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Polissacarídeos/uso terapêutico , Acetilgalactosamina/química , Sulfatos de Condroitina/química , Sulfatos de Condroitina/uso terapêutico , Humanos , Polissacarídeos/química , Ácidos Urônicos/química , Ácidos Urônicos/uso terapêutico
9.
Int J Immunopathol Pharmacol ; 33: 2058738419869489, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31462112

RESUMO

Polysaccharides from Ganoderma lucidum have been demonstrated to possess diverse biological activities. Despite lots of studies on the biological activities of Ganoderma lucidum polysaccharide (GLP), little is known regarding the medicinal potential of low-molecular weight enzymatically hydrolyzed Ganoderma lucidum polysaccharide (EGLP). EGLP was prepared by enzymatic degradation and its potential effects in U14 cervical tumor-bearing mice were evaluated. Both GLP and EGLP delayed tumor growth of the tumor xenograft. The EGLP was superior to native polysaccharide. Moreover, EGLP treatment could effectively protect the immune organs of U14 cervical carcinoma-bearing mice. In addition, the EGLP treatment ameliorated oxidative stress as compared with cyclophosphamide (CTX). Compared with the MC group, the expression of Bcl-2 and COX-2 was obviously decreased by EGLP treatment, whereas the expression of Bax and cleaved caspase-3 was obviously increased. These results indicated that EGLP showed stronger antitumor activity with lower toxic effects and had the potential to be a novel antitumor agent.


Assuntos
Antineoplásicos/uso terapêutico , Polissacarídeos/uso terapêutico , Reishi/química , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Celulase/química , Ciclo-Oxigenase 2/metabolismo , Feminino , Hidrólise , Camundongos , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Carga Tumoral/efeitos dos fármacos , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
10.
Carbohydr Polym ; 223: 115034, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31426965

RESUMO

Fucoidan is a marine-origin sulfated polysaccharide that can show anticancer activity, to which both pro- and anti-angiogenic responses have been reported. Due to this unpredictability, the angiogenic potential of an effective anticancer crude fucoidan (CF), at a concentration of 0.5 mg mL-1, was evaluated. Tube formation assays demonstrated that CF, either administered while endothelial cells seeding or after their adhesion, migration and organization, inhibited or disrupted the formation of tubular-like structures, respectively. Although CF did not significantly reduced vascular endothelial growth factor (VEGF) secretion, it significantly reduced the expression of platelet-derived growth factor (PDGF), compromising the blood vessels maturation. Two chicken embryo chorioallantoic membrane (CAM) assays were performed: one without tumor (CAM I) and the other with an onplanted tumor mass (CAM II); the CF injection reduced the number of blood of vessels and significantly decreased the tumor size, respectively. In vitro and in vivo results support the effectiveness of fucoidan as a natural antitumor therapeutic agent.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Fucus/química , Neovascularização Patológica/tratamento farmacológico , Polissacarídeos/uso terapêutico , Inibidores da Angiogênese/farmacologia , Animais , Linhagem Celular , Galinhas , Membrana Corioalantoide/efeitos dos fármacos , Humanos , Polissacarídeos/farmacologia , Microambiente Tumoral/efeitos dos fármacos
11.
Oxid Med Cell Longev ; 2019: 6869350, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428228

RESUMO

Our previous study has demonstrated the effects of aqueous extract of lily bulb in alleviating menopause-related psychiatric symptoms in ovariectomized (OVX) mice. This study sought to further investigate the psychotropic effects of total polysaccharides of lily bulb (TPLB) against anxiety, depression, and cognitive deterioration and the underlying mechanisms in OVX mice using behavioral, neurochemical, molecular, and proteomic approaches in comparison with estrogen therapy. While TPLB and estradiol showed similar effects in reducing OVX-induced anxiety, depression, and cognitive impairment, the psychotropic effects of TPLB were more closely associated with the predominant activation of estrogen receptors (ERs) and regulation of brain regional neurotransmitters and neurotrophins with minor effects on the uterus. Estradiol had similar potencies in binding affinity at ERα and ERß, which caused widespread genetic and epigenetic effects. In contrast, TPLB displayed a higher affinity at ERß than ERα, triggering the specific Ras/Akt/ERK/CREB signaling pathway without affecting any epigenetic activity. TPLB additionally modulated multiple proteins associated with mitochondrial oxidative stress, but estradiol did not. These results indicate that TPLB has comparable efficacy in reducing menopause-associated neuropsychological symptoms with a better safety profile compared to estrogen therapy. We suggest that TPLB could serve as a novel agent for menopause syndrome.


Assuntos
Lilium/metabolismo , Menopausa/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Ansiedade/patologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Estradiol/metabolismo , Estradiol/farmacologia , Estradiol/uso terapêutico , Receptor alfa de Estrogênio/química , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/química , Receptor beta de Estrogênio/metabolismo , Feminino , Fulvestranto/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Neurotransmissores/análise , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/metabolismo , Polissacarídeos/metabolismo , Polissacarídeos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Útero/efeitos dos fármacos , Útero/metabolismo
12.
Int Immunopharmacol ; 75: 105823, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31422184

RESUMO

Fucoidan, one activator of scavenger receptor class A (SR-A), plays important roles in a variety of biological activities, including anti-inflammatory, antioxidant, and antitumor actions. However, the effects of fucoidan on atopic dermatitis (AD) have not been elucidated. To assess this, 2,4-dinitrofluorobenzene (DNFB)-treated BALB/c mice were painted with fucoidan. Results showed that fucoidan significantly ameliorated ear swelling, improved abdomen skin lesions, and decreased inflammatory cell infiltration. In addition, fucoidan significantly suppressed the serum levels of IgE and IL-4 in DNFB-induced AD mice. The infiltration of CD4+ T cells in skin lesions and spleen was also reduced in fucoidan-treated AD mice. Furthermore, treatment with fucoidan promoted Treg cells but attenuated Th1/17 response in the spleens from DNFB-induced AD mice. Together, these results suggest that fucoidan, a natural seaweed-rich polysaccharide, has a potential therapeutic efficacy in the treatment of AD, correlates with the induction of higher anti-inflammatory response through inducing Treg cells.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Polissacarídeos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Citocinas/imunologia , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/imunologia , Dinitroclorobenzeno , Feminino , Fucus , Imunoglobulina E/sangue , Camundongos Endogâmicos BALB C , Polissacarídeos/farmacologia , Alga Marinha , Pele/efeitos dos fármacos , Pele/imunologia , Baço/efeitos dos fármacos , Baço/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
13.
BMC Complement Altern Med ; 19(1): 161, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277622

RESUMO

BACKGROUND: Cervical cancer is the second most prevalent cancer worldwide. Portulaca oleracea L. polysaccharide (POL-P3b) has been found to have enhancing immune and anti-cervical cancer activity by oral administration. Dendritic cells (DC) play a key roles in regulating intestinal immune homeostasis. In this study, we analyzed the inhibition apoptosis effects of POL-P3b on intestinal DC and relevant mechanisms. METHODS: Intestinal DC was isolated from U14-bearing mice treated with POL-P3b (50 mg/kg, 100 mg/kg and 200 mg/kg, respectively). The effects of POL-P3b on proliferation and inhibiting apoptosis in intestinal DC were evaluated by MTT assay, Hoechst 33342 and Annexin V-FITC/PI staining. Mitochondrial Ca2+ was analyzed using flow cytometry instrument. The potential mechanisms underlying POL-P3b-induced protection of intestinal DC from cervical cancer-induced apoptosis were detected with Western blotting evaluation of expression levels of TLR4 and relevant proteins for apoptotic signaling pathway. RESULTS: We found that a large number of intestinal DC were apoptosis in U14-bearing mice. Treatment with POL-P3b in U14-bearing mice at different doses for 12 d resulted in a significant increase in intestinal DC survival, and the mechanisms were related to inhibiting DC apoptosis. CONCLUSION: Our results suggested that POL-P3b-induced protection against tumor-induced intestinal DC apoptosis through stimulating the TLR4-PI3K/AKT-NF-κB signaling pathway. This study enhanced understanding of the oral administration with POL-P3b exerted on anti-tumor activity and its action mechanism.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Células Dendríticas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Portulaca/química , Administração Oral , Animais , Antineoplásicos Fitogênicos/análise , Antineoplásicos Fitogênicos/uso terapêutico , Cálcio/metabolismo , Carcinoma/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Intestinos/imunologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Transdução de Sinais , Neoplasias do Colo do Útero/tratamento farmacológico
14.
Artif Cells Nanomed Biotechnol ; 47(1): 3194-3201, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31353963

RESUMO

Background: Angelica polysaccharide (AP) is disengaged from the roots of Angelica sinensis. The extensive pathological activities of AP have been discovered in disparate diseases. Nevertheless, the impression of AP in epilepsy (EP) remains unaware. The research attempted to probe the impact of AP on lipopolysaccharide (LPS)-evoked inflammatory injury in HT22 cells. Methods: AP were exploited to stimulate HT22 cells, cell cytotoxicity was monitored by CCK-8 assay. LPS was utilized to administrate HT22 cells to evoke inflammatory injury, meanwhile the involvements of AP in cell proliferation, apoptosis and inflammatory cytokines productions were examined. MicroRNA-10a (miR-10a) inhibitor and its negative control were one by one transfected into HT22 cells, the effect of miR-10a inhibition on LPS- and AP-treated cells was determined. NF-κB and JAK2/STAT3 pathways were ultimately detected. Results: AP promoted cell proliferation, inhibited apoptosis and suppressed IL-1ß, TNF-α and IL-6 productions in LPS-stimulated HT22 cells. Additionally, AP raised miR-10a expression in HT22 cells administration with LPS. These functions of AP in LPS-disposed cells were conversed by miR-10a suppression. Further, AP interdicted NF-κB and JAK2/STAT3 pathways via enhancing miR-10a. Conclusions: Data corroboarted that AP mitigated LPS-evoked inflammatory injury through repression of NF-κB and JAK2/STAT3 pathways by regulating miR-10a in HT22 cells.


Assuntos
Angelica/química , Citoproteção/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , MicroRNAs/genética , Neurônios/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Janus Quinase 2/metabolismo , Camundongos , NF-kappa B/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Polissacarídeos/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Regulação para Cima/efeitos dos fármacos
15.
Med Sci Monit ; 25: 5028-5035, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31280283

RESUMO

BACKGROUND The aim of this study was to evaluate the effects of a new type of dietary fiber - high specific volume polysaccharide (HSVP) - on fecal properties, serum vasoactive intestinal peptide (VIP) concentration, intestinal flora count, and expression of the VIP-cAMP-PKA-AQP3 signaling pathway. MATERIAL AND METHODS Compound diphenoxylate was used in 48 healthy Wistar rats to establish a constipation model. Rats were divided into a normal control group, a constipation model group, an HSVP low-dose group, an HSVP medium-dose group, an HSVP high-dose group, and a fructose control group. We used colony count method, ELISA, WB, and RT-PCR to determine fecal moisture content, fecal hardness, fecal passage time, serum VIP concentration, number of intestinal bacteria, and VIP-cAMP-PKA-AQP3 signal pathway protein expression. RESULTS The constipation model was established successfully. HSVP (the medium dose was 10% and the high dose was 15%) improved fecal moisture content, reduced hardness, shortened fecal emptying time, increased intestinal bacteria, reduced serum VIP concentration, downregulated cAMP and PKAm RNA transcription, reduced protein expression, and reduced intestinal AQP3 expression. CONCLUSIONS HSVP improved constipation, increased the number of intestinal bacteria, and elevated expression of the VIP-cAMP-PKA-AQP3 signaling pathway. The mechanism of HSVP in regulating intestinal water metabolism in constipated rats may occur through the VIP-cAMP-PKA-AQP3 signaling pathway, and be closely related to changes in intestinal bacteria. The important role of the brain-gut-microbiome axis in the pathogenesis of constipation has been confirmed in this study.


Assuntos
Constipação Intestinal/tratamento farmacológico , Fibras na Dieta/uso terapêutico , Intestinos/efeitos dos fármacos , Polissacarídeos/uso terapêutico , Água/metabolismo , Animais , Aquaporina 3/genética , Aquaporina 3/metabolismo , Constipação Intestinal/sangue , Constipação Intestinal/genética , Constipação Intestinal/fisiopatologia , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Fibras na Dieta/farmacologia , Fezes , Microbioma Gastrointestinal/efeitos dos fármacos , Trânsito Gastrointestinal/efeitos dos fármacos , Dureza , Umidade , Polissacarídeos/química , Polissacarídeos/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Transcrição Genética/efeitos dos fármacos , Resultado do Tratamento , Peptídeo Intestinal Vasoativo/sangue , Peptídeo Intestinal Vasoativo/genética
16.
Cell Mol Biol (Noisy-le-grand) ; 65(5): 24-31, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31304902

RESUMO

This study was carried out to evaluate the preventive and curative effects of Pilose antler against osteoporosis due to kidney deficiency, and investigate its potential mechanism of action. A model of osteoporosis due to kidney deficiency was established in rats using bilateral ovariectomy. Pilose antler polypeptide (PAP), Pilose antler polysaccharide (PAP'), and their mixture (PAP+PAP') were separately administered to the rats for 12 weeks, with progynova and xianlingubao tablets (XLGB) as the positive control groups. We determined the bone mineral density (BMD) and uterus Index of the rats. Osteoblastic bone metabolism-related indices in serum and bone tissue were measured with ELISA. Western blotting and RT-PCR were used to investigate the protein and mRNA expressions of Bmp-2, Smad1, Smad5, Runx2 in bone tissue. The morphology of bone tissue was determined using immunohistochemical methods. Compared with control group, PAP, PAP', PAP+PAP' increased BMD and regulated bone metabolism indices in serum and bone tissue. Treatment with Pilose antler up-regulated the mNRA and protein expressions of Bmp-2, Smad1, Smad5 and Runx2. Immunohistochemical staining showed that Bmp-2, Smad1, Smad5 and Runx2 were stained brown, indicating that all of them were positive. There were abnormal changes in the protein expressions of Bmp-2, Smad1, Smad5 and Runx2 in bone tissue, which may be an important mechanism underlying the development of kidney deficiency osteoporosis. Moreover, PAP, PAP' and PAP+PAP' had some preventive effects on osteoporosis, probably via the activation of the Bmp-2/Smad1 and Smad5/Runx2 signaling pathways through induction of high expressions of their mRNAs and proteins.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Osteoporose/etiologia , Peptídeos/farmacologia , Substâncias Protetoras/farmacologia , Insuficiência Renal/complicações , Animais , Densidade Óssea , Proteína Morfogenética Óssea 2/metabolismo , Osso e Ossos/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/prevenção & controle , Ovariectomia/efeitos adversos , Peptídeos/administração & dosagem , Peptídeos/uso terapêutico , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/uso terapêutico , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteína Smad1/metabolismo , Proteína Smad5/metabolismo , Útero/patologia
17.
Carbohydr Polym ; 218: 136-144, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31221314

RESUMO

Aqueous and KCl-soluble polysaccharides were extracted from Laurencia dendroidea (Rhodomelaceae, Ceramiales) and their chemical profile was accessed by anion-exchange chromatography, chemical and spectroscopic analyses. The homogeneous agaran DHS-4 (181.3 × 103 g. mol-1, 21.3% of NaSO3) presents A units mostly 2-sulfated (18.9 mol%), nonsubstituted (15.3 mol%) and 6-O-methylated (10.1 mol%), while B units are l-sugars composed predominantly by galactose 6-sulfate precursor units (19.2 mol%) and 3,6-anhydrogalactose (13.8 mol%), besides non-precursor galactose 6-sulfate units bearing d-xylose substituents on C-3 (8.1 mol%). The crude KCl-soluble DHS agaran (20.5% of NaSO3) inhibited proteolysis and hemolysis induced by Lachesis muta and Bothrops jararaca venoms. DHS was able to inhibit up to 75% the L. muta venom hemorrhagic effect and to reduce the lethality displayed by B. jararaca venom, increasing the mice survival time up to 3 times. Therefore, this agaran has high potential to be used as an additional tool to treat snakebite envenomation.


Assuntos
Proteínas Hemolisinas/antagonistas & inibidores , Hemostáticos/uso terapêutico , Laurencia/química , Polissacarídeos/uso terapêutico , Venenos de Serpentes/antagonistas & inibidores , Ésteres do Ácido Sulfúrico/uso terapêutico , Animais , Bothrops , Hemólise/efeitos dos fármacos , Hemostáticos/química , Hemostáticos/isolamento & purificação , Camundongos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Proteólise/efeitos dos fármacos , Ésteres do Ácido Sulfúrico/química , Ésteres do Ácido Sulfúrico/isolamento & purificação , Viperidae
18.
Curr Med Chem ; 26(35): 6349-6398, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31203794

RESUMO

Carbohydrates are one of the most powerful and versatile classes of biomolecules that nature uses to regulate organisms' biochemistry, modulating plenty of signaling events within cells, triggering a plethora of physiological and pathological cellular behaviors. In this framework, glycan carrier systems or carbohydrate-decorated materials constitute interesting and relevant tools for medicinal chemistry applications. In the last few decades, efforts have been focused, among others, on the development of multivalent glycoconjugates, biosensors, glycoarrays, carbohydrate-decorated biomaterials for regenerative medicine, and glyconanoparticles. This review aims to provide the reader with a general overview of the different carbohydrate carrier systems that have been developed as tools in different medicinal chemistry approaches relying on carbohydrate-protein interactions. Given the extent of this topic, the present review will focus on selected examples that highlight the advancements and potentialities offered by this specific area of research, rather than being an exhaustive literature survey of any specific glyco-functionalized system.


Assuntos
Química Farmacêutica/métodos , Polissacarídeos/uso terapêutico , Animais , Técnicas Biossensoriais/métodos , Dendrímeros/síntese química , Dendrímeros/metabolismo , Dendrímeros/uso terapêutico , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/uso terapêutico , Humanos , Nanopartículas/química , Nanopartículas/metabolismo , Nanopartículas/uso terapêutico , Polissacarídeos/síntese química , Polissacarídeos/metabolismo , Ligação Proteica , Proteínas/metabolismo
19.
J Surg Res ; 243: 265-273, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31254899

RESUMO

BACKGROUND: Ischemia-reperfusion (IR) injury of the small intestine is a serious problem in abdominal aortic aneurysm surgery or small intestine transplantation. Active hexose correlated compound (AHCC) is a popular anti-inflammatory drug in complementary and alternative medicine. The aim of this study was to examine whether pretreatment with AHCC reduces intestinal IR injury. METHODS: Rats were given a normal diet (IR group) or normal diet supplemented with 2% AHCC (IR + AHCC group) ad libitum for 10 d. After 1 d of fasting, the superior mesenteric artery was occluded by clipping for 45 min. Intestinal and blood samples were collected for 1-6 h after reperfusion. The messenger RNA (mRNA) and protein levels of inflammatory factors were analyzed. RESULTS: The IR + AHCC group had reduced mucosal abrasion and significantly increased mucosal thickness of the intestinal tissues 6 h after reperfusion, compared with the IR group. AHCC decreased mRNA expression of inducible nitric oxide synthase (iNOS), cytokine-induced neutrophil chemoattractant 1 and interleukin 6 in the mucosa of the small intestine. AHCC also decreased expression of iNOS protein. Serum levels of cytokine-induced neutrophil chemoattractant 1 and tumor necrosis factor α were decreased in the IR + AHCC group compared with the IR group. Electrophoretic mobility shift assay of mucosal nuclear extracts revealed that AHCC inhibited the activation of nuclear factor kappa B. AHCC also inhibited the expression of iNOS antisense transcript, which stabilizes iNOS mRNA. CONCLUSIONS: Our findings suggest that AHCC reduces expression of inflammatory mediators, in part, by inhibiting nuclear factor kappa B activation. AHCC may have anti-inflammatory effect in patients with intestinal IR injury.


Assuntos
Enteropatias/prevenção & controle , Polissacarídeos/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Animais , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Enteropatias/metabolismo , Enteropatias/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestino Delgado/irrigação sanguínea , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Masculino , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
20.
Mar Drugs ; 17(6)2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31185695

RESUMO

The purpose of this study was to investigate the preventive effects of fucoidan (Fc) and fucoxanthin (Fx) on hyperuricemic rats. Sprague Dawley (SD) rats were randomly assigned to seven groups: a control group, a hyperuricemia (HUA) group, low- and high-dose Fx groups, a Fc group, a combination Fc and Fx group, and a positive control group. Three weeks after the interventions, each group was given potassium oxonate (PO) and hypoxanthine (HX) to induce HUA in all groups except for the control group, and the rats were then sacrificed. Blood and urine were analyzed for biochemical properties, and differences in urine volume were determined. Livers and kidneys were collected to analyze xanthine oxidase (XO) activity and the expression of uric acid (UA) transporter-related proteins (GLUT9, ABCG2, OAT1, URAT1). The results show that HUA was successfully induced by PO/HX after 4 h of administration. The activity of XO was significantly reduced by a combination of Fc and Fx. In the combination group, both ABCG2 and OAT1 increased significantly, whereas GLUT9 and URAT1 decreased significantly. In summary, the combination of Fc and Fx can inhibit the activity of XO in the liver and regulate the expression of proteins related to UA transporter in the kidney to reduce the UA level in serum.


Assuntos
Hiperuricemia/induzido quimicamente , Ácido Oxônico , Polissacarídeos/farmacologia , Xantofilas/farmacologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperuricemia/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/enzimologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Polissacarídeos/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Xantina Oxidase/metabolismo , Xantofilas/uso terapêutico
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