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1.
Int J Biol Macromol ; 142: 545-550, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31715243

RESUMO

Antioxidant and anti-wrinkle effects of sulfated polysaccharides from Celluclast-assisted extract of Hizikia fusiforme (HFPS) make it a good candidate for exploring its cosmeceutical potential. In order to further explore this premise, the anti-inflammatory and anti-melanogenesis effects of HFPS were studied in the present study. HFPS significantly inhibited nitric oxide (NO) generation and improved the cell viability in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. It also decreased the expression of prostaglandin E2 (PGE2) and pro-inflammatory cytokines, and suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 cells. In addition, HFPS also inhibited melanin synthesis in alpha-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 melanoma cells by down-regulating of intracellular levels of tyrosinase and tyrosinase-related protein-1 and -2 (TRP-1 and -2) via inhibiting microphthalmia-associated transcription factor (MITF) expression. These results demonstrate that HFPS possesses strong in vitro anti-inflammatory and anti-melanogenesis effects and can be used in the pharmaceutical and cosmeceutical industries.

2.
Food Chem Toxicol ; 136: 110963, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31715308

RESUMO

Excessive exposure to ultraviolet (UV) irradiation from the sun is the primary environmental factor that causes aging of the skin. Most skin diseases caused by UV are attributed to UVB (280-320 nm). The purpose of this study is to investigate the protective effect of diphlorethohydroxycarmalol (DPHC), isolated from the marine brown alga, Ishige okamurae, against UVB-induced photodamage using both in vitro and in vivo models. Results indicate that DPHC remarkably inhibited commercial collagenase and elastase activities. It also reduced intracellular levels of ROS, improved cell viability and collagen content in UVB-irradiated human dermal fibroblasts (HDF cells). In addition, DPHC significantly inhibited activities of intracellular collagenase and elastase and reduced the expression of matrix metalloproteinases (MMPs) and pro-inflammatory cytokines. These events occurred through regulation of nuclear factor kappa B (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinases (MAPKs) signaling pathways in UVB-irradiated HDF cells. Furthermore, DPHC also protected against in vivo photodamage by decreasing cell death through reducing lipid peroxidation and inflammatory response via decreasing ROS levels in UVB-irradiated zebrafish. In conclusion, DPHC has strong in vitro and in vivo photoprotective effects and has the potential to be used as an ingredient in pharmaceutical and cosmeceutical industries.

3.
J Sci Food Agric ; 100(1): 315-324, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525262

RESUMO

BACKGROUND: In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin-I-converting enzyme (ACE) inhibitory activity of the peptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking. RESULTS: This peptide from protein-rich wastes showed excellent ACE inhibitory activity (IC50  = 2.577 µmol L-1 ) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver-Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C-terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interacts with the S1 and S2 pockets of ACE. CONCLUSION: LSGYGP, with an IC50 value of 2.577 µmol L-1 , has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food-derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension. © 2019 Society of Chemical Industry.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Anti-Hipertensivos/química , Captopril/química , Hipertensão/tratamento farmacológico , Peptídeos/química , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Captopril/administração & dosagem , Ciclídeos , Digestão , Proteínas de Peixes/química , Trato Gastrointestinal/metabolismo , Humanos , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Cinética , Masculino , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Peptídeos/farmacologia , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Hidrolisados de Proteína/química , Hidrolisados de Proteína/metabolismo , Ratos , Ratos Endogâmicos SHR
4.
Int J Mol Sci ; 20(22)2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31698871

RESUMO

Diabetes is associated with vascular complications, such as impaired wound healing and accelerated vascular growth. The different clinical manifestations, such as retinopathy and nephropathy, reveal the severity of enhanced vascular growth known as angiogenesis. This study was performed to evaluate the effects of an extract of Ishige okamurae (IO) and its constituent, Ishophloroglucin A (IPA) on high glucose-induced angiogenesis. A transgenic zebrafish (flk:EGFP) embryo model was used to evaluate vessel growth. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), gap closure, transwell, and Matrigel® assays were used to analyze the proliferation, migration, and capillary formation of EA.hy926 cells. Moreover, protein expression were determined using western blotting. IO extract and IPA suppressed vessel formation in the transgenic zebrafish (flk:EGFP) embryo. IPA attenuated cell proliferation, cell migration, and capillary-like structure formation in high glucose-treated human vascular endothelial cells. Further, IPA down regulated the expression of high glucose-induced vascular endothelial growth factor receptor 2 (VEGFR-2) and downstream signaling molecule cascade. Overall, the IO extract and IPA exhibited anti-angiogenic effects against high glucose-induced angiogenesis, suggesting their potential for use as therapeutic agents in diabetes-related angiogenesis.

5.
Mar Drugs ; 17(11)2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31731426

RESUMO

Ishophloroglucin A (IPA), a component of Ishige okamurae (IO), was previously evaluated to standardize the antidiabetic potency of IO. However, the potential of IPA as a functional food for diabetes prevention has not yet been evaluated. Here, we investigated if 1.35 mg/kg IPA, which is the equivalent content of IPA in 75 mg/kg IO, improved glucose homeostasis in high-fat diet (HFD)-induced diabetes after 12 weeks of treatment. IPA significantly ameliorated glucose intolerance, reducing fasting glucose levels as well as 2 h glucose levels in HFD mice. In addition, IPA exerted a protective effect on the pancreatic function in HFD mice via pancreatic ß-cells and C-peptide. The level of glucose transporter 4 (GLUT4) in the muscles of HFD mice was stimulated by IPA intake. Our results suggested that IPA, which is a component of IO, can improve glucose homeostasis via GLUT4 in the muscles of HFD mice. IO may be used as a functional food for the prevention of diabetes.

6.
Antioxidants (Basel) ; 8(10)2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31635214

RESUMO

It has been reported that enzymatic digestion of algae could improve the yield and enhance the biological activity compared to water and organic extraction. Our previous research indicated that Celluclast-assisted extract of Sargassum fulvellum (SF) possessed higher carbohydrate content and stronger antioxidant activity compared to water and other enzyme-assisted extracts. In the present study, we evaluated the antioxidant activities of polysaccharides from SF (SFPS) in vitro in Vero cells and in vivo in zebrafish. SFPS was obtained by Celluclast-assisted hydrolysis and ethanol precipitation. Results showed that SFPS contained 74.55 ± 1.26% sulfated polysaccharides and effectively scavenged 1, 1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and alkyl radicals. SFPS significantly and dose-dependently scavenged intracellular reactive oxygen species (ROS) and improved cell viability. Further studies indicated that SFPS reduced apoptotic body formation through downregulation of proapoptotic protein (Bax and cleaved caspase-3) levels and upregulation of antiapoptotic protein (Bcl-xL and PARP) levels in 2,2-azobis(2-amidinopropane) hydrochloride (AAPH)-treated Vero cells. In addition, SFPS showed strong protective effect against AAPH-stimulated oxidative stress in vivo in zebrafish, as demonstrated by the improved survival rate, reduced heart rate, and decrease in ROS, cell death, and lipid peroxidation levels. These results suggest that SFPS possesses strong in vitro and in vivo antioxidant activity and can be a potential ingredient in the pharmaceutical and cosmeceutical industries.

7.
Methods Protoc ; 2(2)2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31181680

RESUMO

Maternal tobacco smoking is a recognized risk behavior that has adverse impacts onmaternal and fetal health. However, in some populations, the use of smokeless tobacco exceeds theuse of smoked tobacco. In central Australia, Aboriginal populations utilize wild tobacco plants(Nicotiana spp.) as a smokeless product. These plants are known by a variety of names, one of whichis pituri. The plants are masticated and retained in the oral cavity for extended periods of time andtheir use continues throughout pregnancy, birth, and lactation. In contrast to the evidence related tocombusted tobacco use, there is no evidence as to the effects of pituri use in pregnancy. CentralAustralian Aboriginal women who were at least 28 weeks pregnant were stratified into three tobaccoexposure groups: (a) Pituri chewers, (b) smokers, and (c) non-tobacco users. Routine antenatal andbirth information, pre-existing and pregnancy-related maternal characteristics, fetal characteristics,and biological samples were collected and compared. The biological samples were analysed fortobacco and nicotine metabolite concentrations. Samples from the mother included venous blood,urine, hair and colostrum and/or breast milk. From the neonate, this included Day 1 and Day 3 urineand meconium, and from the placenta, arterial and venous cord blood following delivery. This is thefirst study to correlate the pregnancy outcomes of central Australian Aboriginal women with differenttobacco exposures. The findings will provide the foundation for epidemiological data collection inrelated studies. Note to readers: In this article, the term "Aboriginal" was chosen by central Australianwomen to refer to both themselves and the Aboriginal people in their communities. "Indigenous" waschosen to refer to the wider Australian Aboriginal and Torres Strait Islander people.

8.
Mar Drugs ; 17(5)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31071969

RESUMO

Blood circulation disorders, such as hyperlipidemia and arteriosclerosis, are not easily cured by dietary supplements, but they can be mitigated. Although Ecklonia cava extract (ECE), as dietary supplements, are associated with improving the conditions, there are not many studies verifying the same. In this study, the beneficial effect of ECE and leaf of Ginkgo biloba extract (GBE), which is a well-known dietary supplement, were first confirmed in a diet induced-obese model. Afterwards, 4 phlorotannins were isolated from ECE, and their inhibitory effects on vascular cell dysfunction were validated. Pyrogallol-phloroglucinol-6,6-bieckol (PPB) was selected to be orally administered in two mice models: the diet induced obese model and diet induced hypertension model. After four weeks of administration, the blood pressure of all mice was measured, after which they were subsequently sacrificed. PPB was found to significantly improve blood circulation, including a reduction of adhesion molecule expression, endothelial cell (EC) death, excessive vascular smooth muscle cell (VSMC) proliferation and migration, blood pressure, and lipoprotein and cholesterol levels. Based on the excellent efficacy in diet-induced mouse models of obese and hypertension, our results demonstrate that PPB is a valuable active compound from among the phlorotannins that were isolated and it has the potential to be used in functional foods for improving the blood circulation.


Assuntos
Circulação Sanguínea/efeitos dos fármacos , Dioxinas/farmacologia , Hipertensão/tratamento farmacológico , Obesidade/tratamento farmacológico , Floroglucinol/farmacologia , Pirogalol/farmacologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Pressão Sanguínea , Moléculas de Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dieta , Hipertensão/induzido quimicamente , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Obesidade/induzido quimicamente , Feófitas/química , Extratos Vegetais/farmacologia , RNA Mensageiro , Transdução de Sinais , Taninos/farmacologia
9.
Mar Drugs ; 17(4)2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934943

RESUMO

Obesity is associated with several health complications and can lead to the development of metabolic syndrome. Some of its deleterious consequences are related to insulin resistance, which adversely affects blood glucose regulation. At present, there is a growing concern regarding healthy food consumption, owing to awareness about obesity. Seaweeds are well-known for their nutritional benefits. The brown alga Ishige okamurae (IO) has been studied as a dietary supplement and exhibits various biological activities in vitro and in vivo. The bioactive compounds isolated from IO extract are known to possess anti-obesity and anti-diabetic properties, elicited via the regulation of lipid metabolism and glucose homeostasis. This review focuses on IO extract and its bioactive compounds that exhibit therapeutic effects through several cellular mechanisms in obesity and diabetes. The information discussed in the present review may provide evidence to develop nutraceuticals from IO.


Assuntos
Fármacos Antiobesidade/farmacologia , Hipoglicemiantes/farmacologia , Obesidade/tratamento farmacológico , Feófitas/química , Animais , Glicemia/metabolismo , Suplementos Nutricionais , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/sangue
10.
CNS Neurosci Ther ; 25(4): 486-495, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30264483

RESUMO

AIM: Glioma, with fast growth and progression features, is the most common and aggressive tumor in the central nervous system and is essentially incurable. This study is aimed at inducing neuronal differentiation to suppress glioma cell growth with a single transcription factor. METHODS: Overexpression of transcription factor SRY (sex determining region Y)-box 11 (SOX11) and Zic family member 1 (ZIC1) was, respectively, performed in glioma cells with lentivirus infection. CRISPR/Cas9 technology was used to knock out ZIC1 in U87 cells, and knockout efficiency was identified by Western blotting and Sanger sequencing. Cell cycle and apoptosis were detected by flow cytometry. The downstream targets of SOX11 were analyzed by Affymetrix GeneChip microarrays. qRT-PCR and immunofluorescence technique were used to verify gene targets of genetically modified U87 cells. All the cells were imaged by a fluorescence microscope. Gene expression correlation analysis and overall survival analysis based on TCGA dataset are performed by GEPIA. RESULTS: We induced glioma cells into neuron-like cells to suppress cell growth using a single transcription factor, SOX11 or ZIC1. Besides, we proved that there is a strong correlation between SOX11 and ZIC1. Our study revealed that SOX11 upregulates ZIC1 expression by binding with ZIC1 promoter, and ZIC1 partially mediates SOX11-induced neuronal differentiation in U87 cells. However, SOX11 expression is not regulated by ZIC1. Moreover, high MAP2 expression means better overall survival in TCGA lower grade glioma. CONCLUSION: This study revealed that glioma cells can be reprogrammed into neuron-like cells using a single factor ZIC1, which may be a potential tumor suppressor gene for gliomas treatment.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30519264

RESUMO

Hippocampus is a traditional medicine in China, which can be used for treating tumors, aging, fatigue, thrombosis, inflammation, hypertension, prostatic hyperplasia, and other diseases. 1-(5-Bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] from seahorse (Hippocampus kuda Bleeler) has been shown to suppress proinflammatory responses. In the present study, SE1 potently inhibited gelatin digestion by MMP-9 induced by phorbol 12-myristate 13-acetate (PMA) and migration of human fibrosarcoma HT1080 cells in dose-dependent manner. Moreover, western blot analysis and immunofluorescence analysis have been studied on MAPKs (ERK1/2, p38 kinase and JNK) and NF-κB (p65 and IκB), which refer to the clear molecular mechanism. The results indicated that SE1 significantly suppressed the phosphorylation of mitogen-activated protein kinases (MAPK: p38 kinase and JNK) and NF-κB. Finally, molecular docking result showed SE1 interacts with TYR245 and HIS226 of MMP-9 by hydrogen bond and Pi-Pi bond to suppress MMP-9 activity. This data suggested that the SE1 may possess therapeutic and preventive potential for the treatment of MMP-9 related disorders.

12.
Mar Drugs ; 16(11)2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30413003

RESUMO

Nutraceutical use of algae requires understanding of the diversity and significance of their active compositions for intended activities. Ishige okamurae (I. okamurae) extract is well-known to possess α-glucosidase inhibitory activity; however, studies are needed to investigate its active composition in order to standardize its α-glucosidase inhibitory activity. In this study, we observed the intensity of the dominant compounds of each I. okamurae extract harvested between 2016 and 2017, and the different potency of each I. okamurae extract against α-glucosidase. By comparing the anti-α-glucosidase ability of the dominant compounds, a novel Ishophloroglucin A with highest α-glucosidase inhibitory activity was identified and suggested for standardization of anti-α-glucosidase activity in I. okamurae extract. Additionally, a validated analytical method for measurement of Ishophloroglucin A for future standardization of I. okamurae extract was established in this study. We suggest using Ishophloroglucin A to standardize anti-α-glucosidase potency of I. okamurae and propose the significance of standardization based on their composition for effective use of algae as marine-derived nutraceuticals.


Assuntos
Organismos Aquáticos/química , Suplementos Nutricionais/normas , Inibidores de Glicosídeo Hidrolases/farmacologia , Feófitas/química , Extratos Vegetais/farmacologia , Taninos/química , Taninos/farmacologia , Inibidores de Glicosídeo Hidrolases/análise , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/normas , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/normas , Padrões de Referência , Taninos/análise , Taninos/normas , alfa-Glucosidases/metabolismo
13.
Mar Drugs ; 16(10)2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30308943

RESUMO

Diabetes mellitus causes abnormalities of angiogenesis leading to vascular dysfunction and serious pathologies. Diphlorethohydroxycarmalol (DPHC), which is isolated from Ishige okamurae, is well known for its bioactivities, including antihyperglycemic and protective functions against diabetes-related pathologies. In the present study, the inhibitory effect of DPHC on high glucose-induced angiogenesis was investigated on the human vascular endothelial cell line EA.hy926. DPHC inhibited the cell proliferation, cell migration, and tube formation in cells exposed to 30 mM of glucose to induce angiogenesis. Furthermore, the effect of DPHC against high glucose-induced angiogenesis was evaluated in zebrafish embryos. The treatment of embryos with DPHC suppressed high glucose-induced dilation in the retinal vessel diameter and vessel formation. Moreover, DPHC could inhibit high glucose-induced vascular endothelial growth factor receptor 2 (VEGFR-2) expression and its downstream signaling cascade. Overall, these findings suggest that DPHC is actively involved in the suppression of high glucose-induced angiogenesis. Hence, DPHC is a potential agent for the development of therapeutics against angiogenesis induced by diabetes.


Assuntos
Inibidores da Angiogênese/farmacologia , Glucose/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Feófitas/química , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Peixe-Zebra
14.
Mar Drugs ; 16(7)2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30018254

RESUMO

Our previous study evaluated the antioxidant activities of sulfated polysaccharides from Celluclast-assisted extract of Hizikia fusiforme (HFPS) in vitro in Vero cells and in vivo in zebrafish. The results showed that HFPS possesses strong antioxidant activity and suggested the potential photo-protective activities of HFPS. Hence, in the present study, we investigated the protective effects of HFPS against ultraviolet (UV) B-induced skin damage in vitro in human dermal fibroblasts (HDF cells). The results indicate that HFPS significantly reduced intracellular reactive oxygen species (ROS) level and improved the viability of UVB-irradiated HDF cells in a dose-dependent manner. Furthermore, HFPS significantly inhibited intracellular collagenase and elastase activities, remarkably protected collagen synthesis, and reduced matrix metalloproteinases (MMPs) expression by regulating nuclear factor kappa B (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinases (MAPKs) signaling pathways in UVB-irradiated HDF cells. These results suggest that HFPS possesses strong UV protective effect, and can be a potential ingredient in the pharmaceutical and cosmetic industries.


Assuntos
Fibroblastos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Sargassum/química , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Linhagem Celular , Colagenases/metabolismo , Fibroblastos/metabolismo , Humanos , Metaloproteinases da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Elastase Pancreática/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Pele/metabolismo , Fator de Transcrição AP-1/metabolismo , Raios Ultravioleta/efeitos adversos
15.
Mar Drugs ; 16(1)2018 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-29300311

RESUMO

UV light, especially UVB, is known as a trigger of allergic reaction, leading to mast cell degranulation and histamine release. In this study, phlorotannin Fucofuroeckol-A (F-A) derived from brown algal Ecklonia stolonifera Okamura was evaluated for its protective capability against UVB-induced allergic reaction in RBL-2H3 mast cells. It was revealed that F-A significantly suppress mast cell degranulation via decreasing histamine release as well as intracellular Ca2+ elevation at the concentration of 50 µM. Moreover, the inhibitory effect of F-A on IL-1ß and TNF-α productions was also evidenced. Notably, the protective activity of F-A against mast cell degranulation was found due to scavenging ROS production. Accordingly, F-A from brown algal E. stolonifera was suggested to be promising candidate for its protective capability against UVB-induced allergic reaction.


Assuntos
Antialérgicos/farmacologia , Benzofuranos/farmacologia , Degranulação Celular/efeitos dos fármacos , Dioxinas/farmacologia , Mastócitos/efeitos dos fármacos , Feófitas/metabolismo , Animais , Antialérgicos/química , Antialérgicos/isolamento & purificação , Benzofuranos/química , Benzofuranos/isolamento & purificação , Cálcio/metabolismo , Degranulação Celular/efeitos da radiação , Linhagem Celular Tumoral , Dioxinas/química , Dioxinas/isolamento & purificação , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Histamina/metabolismo , Interleucina-1beta/antagonistas & inibidores , Mastócitos/metabolismo , Mastócitos/efeitos da radiação , Ratos , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Raios Ultravioleta/efeitos adversos
16.
J Pharm Sci ; 107(3): 863-869, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29100864

RESUMO

Poly(ɛ-caprolactone) (PCL) intravaginal matrices were produced for local delivery of a combination of antibacterials, by rapidly cooling a mixture of drug powders dispersed in PCL solution. Matrices loaded with different combinations of metronidazole (10%, 15%, and 20% w/w) and doxycycline (10% w/w) were evaluated in vitro for release behavior and antibacterial activity. Rapid "burst release" of 8%-15% of the doxycycline content and 31%-37% of the metronidazole content occurred within 24 h when matrices were immersed in simulated vaginal fluid at 37°C. The remaining drug was extracted gradually over 14 days to a maximum of 65%-73% for doxycycline and 62%-71% for metronidazole. High levels of antibacterial activity up to 89%-91% against Gardnerella vaginalis and 84%-92% against Neisseria gonorrhoeae were recorded in vitro for release media collected on day 14, compared to "nonformulated" metronidazole and doxycycline solutions. Based on the in vitro data, the minimum levels of doxycycline and metronidazole released from PCL matrices in the form of intravaginal rings into vaginal fluid in vivo were predicted to exceed the minimum inhibitory concentrations for N. gonorrhea (reported range 0.5-4.0 µg/mL) and G. vaginalis (reported range 2-12.8 µg/mL) respectively, which are 2 of the major causative agents for pelvic inflammatory disease.


Assuntos
Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Doxiciclina/uso terapêutico , Metronidazol/uso terapêutico , Doença Inflamatória Pélvica/tratamento farmacológico , Poliésteres/uso terapêutico , Administração Intravaginal , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Feminino , Gardnerella vaginalis/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana/métodos , Neisseria gonorrhoeae/efeitos dos fármacos , Vagina/microbiologia
17.
Mol Med Rep ; 17(1): 2044-2050, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29257215

RESUMO

Fermented microalgae Pavlova lutheri (P. lutheri), the product of Hansenula polymorpha fermentation, exhibited an increase in alkaline phosphatase (ALP) activity in MG­63 osteoblastic cells when compared to that of non­fermented P. lutheri. Fractionation of the fermented P. lutheri resulted in identification of the active peptide [peptide of P. lutheri fermentation (PPLF)] with the sequence of EPQWFL. PPLF significantly increased ALP release from MG­63 cells and mineralization in a dose­dependent manner. In addition, the intracellular levels of ALP and osteocalcin (OCN) proteins were augmented by PPLF treatment. To identify the molecular mechanism underlying the effect of PPLF on osteoblastic differentiation, the phosphorylation levels of the mitogen­activated protein kinases, p38, extracellular signal­regulated kinases 1/2 and Jun, and nuclear factor (NF)­κB were determined following PPLF treatment and the differences in expression were analyzed using p38 and NF­κB selective inhibitors. These results concluded that PPLF from fermented P. lutheri induced osteoblastic differentiation by increasing ALP and OCN release in MG­63 cells via the p38/p65 signaling pathway, indicating that PPLF supplement may be effective for therapeutic application in the field of bone health.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Haptófitas/química , Microalgas/química , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Peptídeos/farmacologia , Fosfatase Alcalina/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Linhagem Celular , Fermentação , Humanos , Osteoblastos/citologia , Osteocalcina/metabolismo , Peptídeos/química
18.
Heliyon ; 3(11): e00469, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29264422

RESUMO

A range of endemic Nicotiana species are chewed as a smokeless tobacco by several Aboriginal populations of Australia. In tobacco research, nicotine to nornicotine conversion is important because nornicotine lowers tobacco quality and is detrimental to health. A diverse group of cytochrome P450 genes with different transcriptional regulations are involved in this conversion. The primary aims of this study were to quantify the pyridine alkaloids and investigate nicotine to nornicotine conversion in laboratory-grown Australian Nicotiana spp. Nicotine, nornicotine, anatabine, anabasine, myosmine and cotinine were quantified in fresh leaves of 24 out of the 26 recognised Australian Nicotiana taxa. Conserved regions of CYP82E related genes were PCR amplified in all studied taxa. The conversion process in fresh leaves was compared with that in leaves that underwent a simulated curing process for species that we identified as being high converters (N. cavicola, N. goodspeedii, N. velutina) and low converters (N. benthamiana, N. excelsior, N. gossei). Agarose gel electrophoretic analysis of CYP82E related genes obtained from the PCR amplification of the cDNA in fresh versus leaves with simulated curing showed about a 3-fold increase in transcript accumulation levels in cured leaves of the high converter species, while the transcript accumulation in N. gossei and N. excelsior maintained a steady basal level and increased by a small amount in N. benthamiana. This suggests the presence of functional loci that are triggered by curing in only high converter species and indicates a potential risk for chewers of high converter species.

19.
Int J Mol Med ; 39(5): 1072-1082, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28393188

RESUMO

In this study, a marine microalga Spirulina sp.-derived protein was hydrolyzed using gastrointestinal enzymes to produce an angiotensin I (Ang I)-converting enzyme (ACE) inhibitory peptide. Following consecutive purification, the potent ACE inhibitory peptide was composed of 7 amino acids, Thr-Met­Glu­Pro­Gly­Lys-Pro (molecular weight, 759 Da). Analysis using the Lineweaver-Burk plot and molecular modeling suggested that the purified peptide acted as a mixed non-competitive inhibitor of ACE. The inhibitory effects of the peptide against the cellular production of vascular dysfunction-related factors induced by Ang II were also investigated. In human endothelial cells, the Ang II-induced production of nitric oxide and reactive oxygen species was inhibited, and the expression of inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) was downregulated when the cells were cultured with the purified peptide. Moreover, the peptide blocked the activation of p38 mitogen­activated protein kinase. These results indicated that this Spirulina sp.-derived peptide warrants further investigation as a potential pharmacological inhibitor of ACE and vascular dysfunction.


Assuntos
Angiotensina II/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Vasos Sanguíneos/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Peptídeos/farmacologia , Peptidil Dipeptidase A/metabolismo , Spirulina , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Sítios de Ligação , Vasos Sanguíneos/metabolismo , Células Endoteliais/metabolismo , Trato Gastrointestinal/metabolismo , Humanos , Hidrólise , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Moleculares , Peso Molecular , Óxido Nítrico/metabolismo , Peptídeos/química , Peptídeos/isolamento & purificação , Peptidil Dipeptidase A/química , Ligação Proteica , Conformação Proteica , Espécies Reativas de Oxigênio/metabolismo , Spirulina/metabolismo
20.
Carbohydr Res ; 440-441: 32-37, 2017 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-28192685

RESUMO

Positive charges of chitooligomer (COS) enable COS to interact with negatively charged anionic groups on the cell surface resulting in an improvement in the biological activity of COS and its derivatives. In this study, 4-hydroxybenzaldehyde-COS (HB-COS) was synthesized and investigated for its abilities against H2O2-induced oxidative stress in microglia BV-2 cells. Under oxidative stress, HB-COS significantly attenuated reactive oxygen species (ROS) generation and DNA oxidation, and upregulated the protein levels of antioxidative enzymes. HB-COS is therefore proposed as a potential protective agent against neuronal damage.


Assuntos
Antioxidantes/farmacologia , Benzaldeídos/farmacologia , Quitina/análogos & derivados , Peróxido de Hidrogênio/antagonistas & inibidores , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Antioxidantes/síntese química , Benzaldeídos/química , Catalase/metabolismo , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Quitina/síntese química , Quitina/farmacologia , Fluoresceínas/química , Corantes Fluorescentes/química , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Peróxido de Hidrogênio/farmacologia , Camundongos , Microglia/citologia , Microglia/metabolismo , Fármacos Neuroprotetores/síntese química , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Eletricidade Estática , Superóxido Dismutase/metabolismo
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