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1.
ACS Appl Mater Interfaces ; 12(4): 4849-4858, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31904212

RESUMO

The transport of ionic species through nanochannels plays an important role in the basic research and practical application of nanofluidic devices. Here, a visualized CdSe@ZIF-8/PAA nanochannel membrane was created by employing in situ growth of zeolite imidazole skeleton (ZIF-8) and CdSe quantum dots (CdSe QDs) on a porous anodized aluminum oxide (PAA) membrane surface using CdSe QDs, 2-methylimidazole, and zinc nitrate as the precursor solvents. ZIF-8 is a kind of metal-organic framework, a microporous material that possesses strong metal adsorption capacity. In addition, CdSe quantum dots have fluorescent properties. The nanochannel membrane detects copper ions (Cu2+) by quenching the fluorescence intensity by the interaction between Cu2+ and Se and S atoms. The direct potential of 5 V was applied to achieve Cu2+ enrichment at the nanochannel interface, and the fluorescence change was observed. The CdSe@ZIF-8/PAA nanochannel membrane has a good linear range of concentration (0.01 pM-1 µM) for Cu2+ detection. With the help of nanochannel enrichment, its detection limit reaches 4 fM. In addition, this nanochannel membrane has good selectivity for Cu2+.

2.
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
3.
Food Nutr Res ; 632019.
Artigo em Inglês | MEDLINE | ID: mdl-31762729

RESUMO

Introduction: A previous study has shown that Ala-Thr-Pro-Gly-Asp-Glu-Gly (ATPGDEG) peptide identified from boiled abalone by-products has high antioxidant activities and antihypertensive effect. Objective: In this study, we further investigated its antiphotoaging activities by ultraviolet B (UVB)-induced HaCaT cells. Result: UVB irradiation significantly increased the content of intercellular reactive oxygen species (ROS) and the production of matrix metalloproteinases (MMPs) in HaCaT cells and decreased its content of collagen. First, the generation of intercellular ROS was reduced by abalone peptide in UVB-induced HaCaT cells. And activities of MMP-1 and MMP-9 were reduced by abalone peptide in a dose-dependent manner. Furthermore, western blot analysis demonstrated that abalone peptide downregulated the expression of p38, c-Jun N-terminal kinases, and extracellular signal-regulated kinases via mitogen-activated protein kinases (MAPKs) and NF-κB signaling to protect type I pro collagen and DNA damage. Molecular docking simulation confirms that abalone peptide inhibited activities of MMP-1 and MMP-9 by docking their active site, among them N-terminal Ala, C-terminal Gly, and Pro at the third position of N-terminal made a great contribution. Conclusion and recommendation: Abalone peptide could protect type I procollagen synthesis in UVB-irradiated HaCaT cells, and it is a potential peptide for the treatment of skin photoaging in the future.

4.
J Agric Food Chem ; 67(32): 8855-8867, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31343893

RESUMO

Abalone (Haliotis discus hannai) is a precious seafood in the market. It has been reported that biological active substances derived from abalone have anti-oxidative, anti-inflammatory, anti-bacterial, and anti-thrombosis potential. However, there were few studies to assess whether they have anti-cancer potential. In this study, we evaluated the anti-metastasis and anti-pro-angiogenic factors and mechanism of action of boiled abalone byproduct peptide (BABP, EMDEAQDPSEW) in human fibrosarcoma (HT1080) cells and human umbilical vein endothelial cells (HUVECs). The results demonstrated that BABP treatment significantly lowers migration and the invasion of HT1080 cells and HUVECs. BABP inhibits phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP) expression and activity by blocking mitogen-activated protein kinases (MAPKs) and NF-κB signaling and hypoxia-induced vascular endothelial growth factor (VEGF) secretion and hypoxia inducible factor (HIF)-1α accumulation through suppressing the AKT/mTOR signal pathway. BABP treatment inhibits VEGF-induced VEGFR-2 expression and tube formation in HUVECs. The effect of BABP on anti-metastatic and anti-vascular activity in HT1080 cells and HUVECs revealed that BABP may be a potential pharmacophore for tumor therapy in the future.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Gastrópodes/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Peptídeos/farmacologia , Resíduos/análise , Inibidores da Angiogênese/química , Inibidores da Angiogênese/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Metástase Neoplásica , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/fisiopatologia , Peptídeos/química , Peptídeos/isolamento & purificação , Frutos do Mar/análise , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
5.
Mar Drugs ; 17(7)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340575

RESUMO

Angiotensin II (Ang II) is closely involved in endothelial injury during the development of hypertension. In this study, the protective effects of the tilapia by-product oligopeptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) on oxidative stress and endothelial injury in Angiotensin II (Ang II)-stimulated human umbilical vein endothelial cells (HUVEC) were evaluated. LSGYGP dose-dependently suppressed the fluorescence intensities of nitric oxide (NO) and reactive oxygen species (ROS), inhibited the nuclear factor-kappa B (NF-κB) pathway, and reduced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and endothelin-1 (ET-1) expression, as shown by western blot. In addition, it attenuated the expression of gamma-glutamyltransferase (GGT) and heme oxygenase 1 (HO-1), as well as increasing superoxide dismutase (SOD) and glutathione (GSH) expression through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Other experiments revealed that LSGYGP increased the apoptotic inhibition ratio between cleaved-caspase-3/procaspase-3, reduced expressions of pro-apoptotic ratio between Bcl-2/Bax, inhibited phosphorylation of mitogen-activated protein kinases (MAPK), and increased phosphorylation of the serine/threonine kinase (Akt) pathway. Furthermore, LSGYGP significantly decreased Ang II-induced DNA damage in a comet assay, and molecular docking results showed that the steady interaction between LSGYGP with NF-κB may be attributed to hydrogen bonds. These results suggest that this oligopeptide is effective in protecting against Ang II-induced HUVEC injury through the reduction of oxidative stress and alleviating endothelial damage. Thus, it has the potential for the therapeutic treatment of hypertension-associated diseases.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Hipertensão/complicações , Oligopeptídeos/farmacologia , Tilápia , Doenças Vasculares/prevenção & controle , Angiotensina II/toxicidade , Animais , Endotélio Vascular/citologia , Endotélio Vascular/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipertensão/patologia , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/química , NF-kappa B/metabolismo , Oligopeptídeos/química , Estresse Oxidativo/efeitos dos fármacos , Ligação Proteica , Transdução de Sinais/efeitos dos fármacos , Doenças Vasculares/patologia
6.
Photochem Photobiol ; 95(6): 1424-1432, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31230361

RESUMO

In this study, we investigated the protective effects of a peptide (YGDEY, Tyr-Gly-Asp-Glu-Tyr) isolated from tilapia skin gelatin hydrolysates (TGHs), against UVB-induced photoaging in human keratinocytes (HaCaT) cells. Results showed that YGDEY significantly decreased levels of intracellular reactive oxygen species (ROS), increased antioxidant factors (Superoxide Dismutase, SOD and Glutathione, GSH) expression and maintained balance between GSH and GSSG in HaCaT cells. Comet assay shows that YGDEY can protect DNA from oxidative damage. Furthermore, it significantly inhibited MMP-1 (collagenase) and MMP-9 (gelatinase) expression and increased Type I procollagen production. In addition, the molecular docking study showed that YGDEY may form active sites with MMP-1 and MMP-9. Moreover, Western blot analysis was utilized to measure the protein levels of UVB-induced mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways. Therefore, these results suggested that YGDEY has a therapeutic effectiveness in prevention of UVB-induced cellular damage, and it is a candidate worthy of being developed as a potential natural antioxidant and food additive.

7.
Anal Chem ; 91(13): 8184-8191, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31140271

RESUMO

The transport of ions in nanochannels has received considerable interest owing to the unique transport properties and potential applications. In this study, ultrasmall nanochannels (0.8-1.2 nm) were fabricated in porous anodized aluminum (PAA) membrane in situ growth. 2-Methylimidazole and zinc nitrate were used as the reaction precursor solkution, and then zeolitic imidazolate framework (ZIF-8) nanoparticles were sufficiently filled in PAA nanochannels to form a ZIF-8/PAA nanochannels composite membrane. Because ZIF-8 is a microporous material and has a strong ability to adsorb heavy metals, the composite membrane was used as a biosensor to detect lead ion (Pb2+) by the coordination interaction between Pb2+ and nitrogen atoms. The detection limit reached to 0.03 nM due to the enrichment of nanochannels under electric field. The sensor has a good linear range for Pb2+ from 10 nM to 10 µM.

8.
Mar Drugs ; 17(4)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022939

RESUMO

Vasculogenic mimicry (VM) formed by tumor cells plays a vital role in the progress of tumor, because it provides nutrition for tumor cells and takes away the metabolites. Therefore, the inhibition of VM is crucial to the clinical treatment of tumors. In this study, we investigated the anti-tumor effect of a novel peptide, KVEPQDPSEW (AATP), isolated from abalone (Haliotis discus hannai) on HT1080 cells by migration, invasion analysis and the mode of action. The results showed that AATP effectively inhibited MMPs by blocking MAPKs and NF-κB pathways, leading to the downregulation of metastasis of tumor cells. Moreover, AATP significantly inhibited VM and pro-angiogenic factors, including VEGF and MMPs by suppression of AKT/mTOR signaling. In addition, molecular docking was used to study the interaction of AATP and HIF-1α, and the results showed that AATP was combined with an active site of HIF-1α by a hydrogen bond. The effect of AATP on anti-metastatic and anti-vascular in HT1080 cells revealed that AATP may be a potential lead compound for treatment of tumors in the future.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Gastrópodes/química , Neoplasias/tratamento farmacológico , Peptídeos/farmacologia , Adulto , Inibidores da Angiogênese/química , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Metaloproteinases da Matriz/metabolismo , NF-kappa B/metabolismo , Metástase Neoplásica , Neoplasias/irrigação sanguínea , Neoplasias/metabolismo , Neoplasias/patologia , Proteína Oncogênica v-akt/metabolismo , Peptídeos/química , Peptídeos/isolamento & purificação , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Esferoides Celulares/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , eIF-2 Quinase/metabolismo
9.
J Neuroimmunol ; 330: 143-151, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30884275

RESUMO

Seahorse has been used as a traditional medicine in Southeast Asian countries for a long time. A compound, 2'-Hydroxy-5'-Methoxyacetophenone (2H5M) isolated from seahorse, Hippocampus kuda, was tested for its anti-inflammatory effect in lipopolysaccharides (LPS)-stimulated BV-2 cells and RAW264.7 cells. MTT assay indicated that 2H5M has no cytotoxicity on two kinds of cells. The concentration of nitric oxide (NO) measured by Griess Reaction System showed that 2H5M could significantly inhibit the NO concentration. The ELISA results showed that 2H5M could suppress the secretion of TNF-α in a dose-dependent manner. Moreover, western blot analysis was utilized to measure the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways. Electrophoretic mobility shift assay (EMSA) demonstrated that 2H5M reduced NF-κB DNA binding activity. Furthermore, the molecular docking study showed that 2H5M can form active sites with NF-κB. Collectively, these results indicated that 2H5M possesses anti-inflammatory effects and may have a potential application in inflammatory disorders in the future.


Assuntos
Anti-Inflamatórios/farmacologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios/isolamento & purificação , Relação Dose-Resposta a Droga , Mediadores da Inflamação/antagonistas & inibidores , Camundongos , NF-kappa B/antagonistas & inibidores , Células RAW 264.7 , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia , Smegmamorpha
10.
Nutrients ; 11(2)2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30781878

RESUMO

According to a previous study, YGDEY from tilapia fish skin gelatin hydrolysates has strong free radical scavenging activity. In the present study, the protective effect of YGDEY against oxidative stress induced by ethanol in HepG2 cells was investigated. First, cells were incubated with YGDEY (10, 20, 50, and 100 µM) to assess cytotoxicity, and there was no significant change in cell viability. Next, it was established that YGDEY decreased the production of reactive oxygen species (ROS). Western blot results indicated that YGDEY increased the levels of superoxide dismutase (SOD) and glutathione (GSH) and decreased the expression of gamma-glutamyltransferase (GGT) in HepG2 cells. It was then revealed that YGDEY markedly reduced the expressions of bax and cleaved-caspase-3 (c-caspase-3); inhibited phosphorylation of Akt, IκB-α, p65, and p38; and increased the level of bcl-2. Moreover, the comet assay showed that YGDEY effectively decreased the amount of ethanol-induced DNA damage. Thus, YGDEY protected HepG2 cells from alcohol-induced injury by inhibiting oxidative stress, and this may be associated with the Akt/nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signal transduction pathways. These results demonstrate that YGDEY from tilapia fish skin gelatin hydrolysates protects HepG2 cells from oxidative stress, making it a potential functional food ingredient.


Assuntos
Etanol/toxicidade , Gelatina/química , Peptídeos/farmacologia , Tilápia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Peptídeos/química , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Pele/química
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.
ACS Appl Mater Interfaces ; 10(36): 30214-30226, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30113815

RESUMO

The microstructure of hydroxyapatite is known to influence cellular behavior, can be used as a substrate for osteoblast growth, and exploited as a drug-release platform. However, easy delamination and self-decomposition of hydroxyapatite caused by poor adhesion with substrates are the main problems currently. In this paper, we successfully fabricated titanium dioxide/strontium-doped hydroxyapatite (TiO2/SrHA) composite scaffolds by self-generated strontium-substituted hydroxyapatite microspheres in TiO2 nanotubes. Moreover, the active compound 1-(5-bromo-2-hydroxy-methoxyphenyl)-ethanone (BHM) from Seahorse ( Hippocampus kuda Bleeler) was loaded in this scaffold, and the controlled release kinetics of BHM was studied. It was found that in the first 5 h, the release concentration and time of BHM had a good linear relationship, and the correlation coefficient reached 0.98. TiO2/SrHA/BHM composites exhibited favorable cytocompatibility at a given concentration of BHM (20 µmol/L). Compared to pure SrHA, TiO2 nanotubes, and traditional TiO2/SrHA composites, superior cytocompatibility (cell adhesion and proliferation) of MC3T3-E1 was obtained on TiO2/SrHA/BHM composites. The expression levels of osteogenic marker genes such as alkaline phosphatase, osteopontin, osteocalcin, runt-related transcription factor 2, and collagen I are also upregulated to varying degrees. This TiO2/SrHA composite scaffold-mediated phenolic compound BHM could be applied in bone tissue repair.


Assuntos
Acetofenonas/química , Hidroxiapatitas/farmacologia , Osteoblastos/efeitos dos fármacos , Estrôncio/farmacologia , Titânio/farmacologia , Células 3T3 , Animais , Proliferação de Células/efeitos dos fármacos , Hidroxiapatitas/química , Camundongos , Osteoblastos/citologia , Osteogênese/genética , Smegmamorpha , Estrôncio/química , Titânio/química
13.
Mar Drugs ; 16(6)2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29880753

RESUMO

Butyrolactone-I (ZB5-1) from the coral-derived fungus Aspergillus terreus was investigated in this study to estimate its anti-neuroinflammatory effects on lipopolysaccharide (LPS)-induced BV-2 microglia cells. MTT assay indicated that ZB5-1 in tested concentrations had no cytotoxicity on BV-2 cells, and significantly reduced the production of nitric oxide (NO), measured using Griess reagent, and interleukin-1 beta (IL-1ß), detected by enzyme-linked immunosorbent assay (ELISA). ZB5-1 also down-regulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner by Western blot analysis. Moreover, the effect of ZB5-1 on the nuclear factor-κB (NF-κB) signaling pathway was studied via the expression of phosphorylation of NF-κB p65 and inhibitor of NF-κB (IκB), and the nuclear translocation of NF-κB p65 respectively. The results showed that ZB5-1 could inhibit the phosphorylation of p65 and IκB. Furthermore, molecular docking study suggested that ZB5-1 bound at the active sites of NF-κB to prevent its translocation to the nucleus. Therefore, we suggest ZB5-1 has a potential to reduce the anti-inflammatory response in LPS-induced BV-2 cells.


Assuntos
4-Butirolactona/análogos & derivados , Antozoários/microbiologia , Aspergillus/metabolismo , Inflamação/tratamento farmacológico , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , 4-Butirolactona/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Proteínas I-kappa B/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos
14.
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
15.
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
16.
Int J Mol Med ; 37(1): 243-50, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26718326

RESUMO

The aim of the present study was to examine whether the intestine gastrointestinal (GI) digests of abalone [Haliotis discus hannai (H. discus hannai)] modulate inflammatory responses and to elucidate the mechanisms involved. The GI digests of the abalone intestines were fractionated into fractions I (>10 kDa), II (5-10 kDa) and Ⅲ (<5 kDa). Of the abalone intestine GI digests (AIGIDs), fraction Ⅲ inhibited the passive cutaneous anaphylaxis (PCA) reaction in mice. Subsequently, a bioactive peptide [abalone intestine GI digest peptide (AIGIDP)] isolated from fraction Ⅲ was determined to be 1175.2 Da, and the amino acid sequence was found to be PFNQGTFAS. We noted that the purified nonameric peptide (AIGIDP) attenuated the phorbol­12­myristate 13-acetate plus calcium ionophore A23187 (PMACI)-induced histamine release and the production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-6 in human mast cells (HMC-1 cells). In addition, we also noted that AIGIDP inhibited the PMACI­induced activation of nuclear factor­κB (NF-κB) by suppressing IκBα phosphorylation and that it suppressed the production of cytokines by decreasing the phosphorylation of JNK. The findings of our study indicate that AIGIDP exerts a modulatory, anti-allergic effect on mast cell-mediated inflammatory diseases.


Assuntos
Antialérgicos/farmacologia , Produtos Biológicos/farmacologia , Gastrópodes/química , Liberação de Histamina/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Antialérgicos/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/imunologia , Trato Gastrointestinal/química , Humanos , Imunoglobulina E/imunologia , Mediadores da Inflamação/imunologia , Masculino , Mastócitos/citologia , Mastócitos/imunologia , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/imunologia , NF-kappa B/imunologia , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Peptídeos/isolamento & purificação
17.
Pharm Biol ; 52(7): 926-32, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24920235

RESUMO

CONTEXT: Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown. OBJECTIVE: The purpose of the present study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated local allergic reaction in animals, as well as to elucidate the effects of CAPE on mast cells in vitro. MATERIALS AND METHODS: To investigate the bioactive potential of CAPE (10 or 20 µM), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24 h in the presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme-linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis, electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used. RESULTS: CAPE (10 mg/kg) inhibited local IgE-mediated allergic reactions (0.164 versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20 µM) attenuated PMACI-stimulated histamine release (3146.42 versus 2564.83 pg/ml) and the production of inflammatory cytokines, such as interleukin (IL)-1ß (4.775 versus 0.713 pg/ml, IC50 = 6.67 µM), IL-6 (4771.5 versus 449.1 pg/ml, IC50 = 5.25 µM), and IL-8 (5991.7 versus 2213.1 pg/ml, IC50 = 9.95 µM) in HMC-1 cells. In activated HMC-1 cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-κB activation by suppressing IκBα phosphorylation and its degradation. DISCUSSION AND CONCLUSION: Our results indicated that CAPE can modulate mast cell-mediated allergic disease.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ácidos Cafeicos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Álcool Feniletílico/análogos & derivados , Animais , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/efeitos dos fármacos , Histamina/metabolismo , Liberação de Histamina/efeitos dos fármacos , Humanos , Hipersensibilidade/prevenção & controle , Imunoglobulina E/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Mastócitos/citologia , Mastócitos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Álcool Feniletílico/farmacologia , Fosforilação/efeitos dos fármacos
18.
Curr Microbiol ; 69(4): 445-50, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24842302

RESUMO

A strain designated as S85(T) was isolated from a seaweed collected from coastal area of Chuuk State in Micronesia. The strain was gram-negative, rod-shaped, and non-motile and formed yellow colonies on the SWY agar (0.2 % yeast extract and 1.5 % agar in seawater) and Marine agar 2216. The strain grew at pH 5-9 (optimum, pH 8), at 15-40 °C (optimum, 25-28 °C), and with 1-9 % (w/v) NaCl (optimum, 3 %). The phylogenetic analysis based on 16S rRNA gene sequence showed that strain S85(T) was related to Lutibacter litoralis CL-TF09(T) and Maritimimonas rapanae A31(T) with 91.4 % and with 90.5 % similarity, respectively. The dominant fatty acids were iso-C15:0, iso-C15:0 3-OH and iso-C17:0 3-OH, C16:0 3-OH and summed feature 3 (C16:1 ω7c and/or iso-C15:0 2-OH). The major isoprenoid quinone was MK-6. The DNA G+C content of the type strain was 34.6 mol %. The major polar lipids were phosphatidylethanolamine, an unknown glycolipid and two unknown polar lipids. Based on this polyphasic taxonomic data, strain S85(T) stands for a novel species of a new genus, and we propose the name Ochrovirga pacifica gen. nov., sp. nov. The type strain of O. pacifica is S85(T) (=KCCM 90106 =JCM 18327(T)).


Assuntos
Flavobacteriaceae/isolamento & purificação , Água do Mar/microbiologia , Alga Marinha/microbiologia , Ágar/metabolismo , Composição de Bases , Ácidos Graxos/metabolismo , Flavobacteriaceae/classificação , Flavobacteriaceae/genética , Flavobacteriaceae/imunologia , Flavobacteriaceae/metabolismo , Micronésia , Dados de Sequência Molecular , Filogenia
19.
Mar Drugs ; 12(1): 69-87, 2013 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-24368570

RESUMO

Gliotoxin, a secondary metabolite produced by marine fungus Aspergillus sp., possesses various biological activities including anticancer activity. However, the mechanism underlying gliotoxin-induced cytotoxicity on human cervical cancer (Hela) and human chondrosarcoma (SW1353) cells remains unclear. In this study, we focused on the effect of gliotoxin induction on apoptosis, the activating expressions of caspase family enzymes in the cells. Apoptotic cell levels were measured through DAPI and Annexin V/Propidium Iodide (PI) double staining analysis. The apoptotic protein expression of Bcl-2 and caspase family was detected by Western blot in Hela and SW1353 cells. Our results showed that gliotoxin treatment inhibited cell proliferation and induced significant morphological changes. Gliotoxin induced apoptosis was further confirmed by DNA fragmentation, chromatin condensation and disrupted mitochondrial membrane potential. Gliotoxin-induced activation of caspase-3, caspase-8 and caspase-9, down-regulation of Bcl-2, up-regulation of Bax and cytochromec (cyt c) release showed evidence for the gliotoxin activity on apoptosis. These findings suggest that gliotoxin isolated from marine fungus Aspergillus sp. induced apoptosis in Hela and SW1353 cells via the mitochondrial pathway followed by downstream events leading to apoptotic mode of cell death.


Assuntos
Antineoplásicos , Apoptose/efeitos dos fármacos , Aspergillus/química , Produtos Biológicos/farmacologia , Gliotoxina/isolamento & purificação , Gliotoxina/farmacologia , Anexina A5 , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/biossíntese , Caspases/biossíntese , Linhagem Celular Tumoral , Condrossarcoma/tratamento farmacológico , Corantes , Fragmentação do DNA , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , Indóis , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fosfatidilserinas/metabolismo , Propídio , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Neoplasias do Colo do Útero/tratamento farmacológico
20.
Food Chem ; 141(1): 503-9, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23768386

RESUMO

Abalone (Haliotis discus hannai) is a marine gastropod, and an important fishery and food industrial resource that is massively maricultured in Asia, Africa, Australia and America. However, its health benefits have rarely been studied for nutraceutical and pharmaceutical application. In this study, the purified abalone oligopeptide (AOP) with anti-matrix metalloproteinases (anti-MMPs) effects was isolated from the digests of abalone intestine using recycle HPLC with a JAI W253 column and an OHpak SB-803 HQ column. The AOP was identified as Ala-Glu-Leu-Pro-Ser-Leu-Pro-Gly (MW=782.4 Da) with a de novo peptide sequencing technique using a tandem mass spectrometer. The AOP exhibited a specific inhibitory effect against MMP-2/-9 activity and attenuated protein expression of p50 and p65 in the human fibrosarcoma (HT1080) cells, dose-dependently. The results presented illustrate that the AOP could inhibit MMP-2/-9 expression in HT1080 cells via the nuclear factor-kappaB (NF-κB)-mediated pathway. This data suggest that the AOP from H. discus hannai intestine may possess therapeutic and preventive potential for the treatment of MMPs-related disorders such as angiogenesis and cardiovascular diseases.


Assuntos
Gastrópodes/química , Inibidores de Metaloproteinases de Matriz/química , Oligopeptídeos/química , Sequência de Aminoácidos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Trato Gastrointestinal/química , Expressão Gênica/efeitos dos fármacos , Humanos , Inibidores de Metaloproteinases de Matriz/isolamento & purificação , Inibidores de Metaloproteinases de Matriz/farmacologia , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Dados de Sequência Molecular , Oligopeptídeos/isolamento & purificação , Oligopeptídeos/farmacologia
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