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1.
Infect Genet Evol ; 84: 104451, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32640381

RESUMO

WHO has declared the outbreak of COVID-19 as a public health emergency of international concern. The ever-growing new cases have called for an urgent emergency for specific anti-COVID-19 drugs. Three structural proteins (Membrane, Envelope and Nucleocapsid protein) play an essential role in the assembly and formation of the infectious virion particles. Thus, the present study was designed to identify potential drug candidates from the unique collection of 548 anti-viral compounds (natural and synthetic anti-viral), which target SARS-CoV-2 structural proteins. High-end molecular docking analysis was performed to characterize the binding affinity of the selected drugs-the ligand, with the SARS-CoV-2 structural proteins, while high-level Simulation studies analyzed the stability of drug-protein interactions. The present study identified rutin, a bioflavonoid and the antibiotic, doxycycline, as the most potent inhibitor of SARS-CoV-2 envelope protein. Caffeic acid and ferulic acid were found to inhibit SARS-CoV-2 membrane protein while the anti-viral agent's simeprevir and grazoprevir showed a high binding affinity for nucleocapsid protein. All these compounds not only showed excellent pharmacokinetic properties, absorption, metabolism, minimal toxicity and bioavailability but were also remain stabilized at the active site of proteins during the MD simulation. Thus, the identified lead compounds may act as potential molecules for the development of effective drugs against SARS-CoV-2 by inhibiting the envelope formation, virion assembly and viral pathogenesis.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Proteínas do Nucleocapsídeo/química , Proteínas do Envelope Viral/química , Proteínas da Matriz Viral/química , Vírion/efeitos dos fármacos , Sequência de Aminoácidos , Antivirais/química , Betacoronavirus/genética , Betacoronavirus/metabolismo , Sítios de Ligação , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Doxiciclina/química , Doxiciclina/farmacologia , Expressão Gênica , Humanos , Cinética , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteínas do Nucleocapsídeo/antagonistas & inibidores , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/metabolismo , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Quinoxalinas/química , Quinoxalinas/farmacologia , Rutina/química , Rutina/farmacologia , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Simeprevir/química , Simeprevir/farmacologia , Termodinâmica , Proteínas do Envelope Viral/antagonistas & inibidores , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Proteínas da Matriz Viral/antagonistas & inibidores , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/metabolismo , Vírion/genética , Vírion/metabolismo
2.
Int J Food Microbiol ; 328: 108664, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32474229

RESUMO

To control Pseudomonas and Shewanella as important psychrotrophic spoilage bacteria in fish meat, we used ethanolic extracts of oregano (Origanum vulgare subsp. vulgare) and nettle (Urtica dioica), with phytochemical characterisation of the extracts and their bioactive compounds. Liquid chromatography coupled with photodiode array detection and electrospray ionisation-mass spectrometry was used for qualitative compositional determination of the extracts. Four main compounds were identified in the oregano extract, with rosmarinic acid the most abundant, followed by three glycosylated phenolics, one of which is reported for the first time in O. vulgare: 4'-O-ß-d-glucopyranosyl-3',4'-dihydroxybenzyl-4-hydroxybenzoate. Six main compounds were identified in the nettle extract, as caffeoylmalic acid and five flavonoid glycosides. These oregano and nettle ethanolic extracts showed in-vitro antimicrobial activities against selected Pseudomonas and Shewanella strains in broth and fish meat homogenate when evaluated at two inoculum concentrations. The antimicrobial activities were more pronounced for the nettle extract at the lower inoculum concentration, and for both the Shewanella strains. Growth inhibition in the fish meat homogenate was evaluated at 3.13 mg/mL and 1.56 mg/mL at 5 °C. Again, the nettle extract showed greater antimicrobial activity, which was seen as the lowest maximum growth rate, followed by the oregano extract, which was inhibitory only at 3.13 mg/mL. Finally, the extracts were applied to fish meat that was then stored at 5 °C for 9 days. Evaluation here was for the counts of the mesophilic, psychrotrophic, Pseudomonas and H2S producers. These confirmed the better antimicrobial effects of the nettle extract, especially against the H2S-producing bacteria, which included Shewanella. Both of the extracts were rich in glycosides of flavonoids and phenolic acids. The enzymatic activities of the Pseudomonas and Shewanella spoilage bacteria and their actions on the phenolic glycosides from natural sources will be further investigated.


Assuntos
Doenças dos Peixes/tratamento farmacológico , Origanum/química , Extratos Vegetais/farmacologia , Pseudomonas/efeitos dos fármacos , Shewanella/efeitos dos fármacos , Urtica dioica/química , Animais , Ácidos Cafeicos/farmacologia , Cinamatos/farmacologia , Depsídeos/farmacologia , Peixes/microbiologia , Flavonoides , Microbiologia de Alimentos , Hidroxibenzoatos/farmacologia , Malatos/farmacologia , Fenóis/química , Alimentos Marinhos/microbiologia , Espectrometria de Massas por Ionização por Electrospray
3.
PLoS One ; 15(5): e0232832, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401800

RESUMO

The treatment of human colorectal cancer (CRC) cells through suppressing the abnormal survival signaling pathways has recently become a significant area of focus. In this study, our results demonstrated that decyl caffeic acid (DC), one of the novel caffeic acid derivatives, remarkedly suppressed the growth of CRC cells both in vitro and in vivo. The inhibitory effects of DC on CRC cells were investigated in an in vitro cell model and in vivo using a xenograft mouse model. CRC cells were treated with DC at various dosages (0, 10, 20 and 40 µM), and cell survival, the apoptotic index and the autophagy level were measured using an MTT assay and flow cytometry analysis, respectively. The signaling cascades in CRC were examined by Western blot assay. The anti-cancer effects of DC on tumor growth were examined by using CRC HCT-116 cells implanted in an animal model. Our results indicated that DC differentially suppressed the growth of CRC HT-29 and HCT-116 cells through an enhancement of cell-cycle arrest at the S phase. DC inhibited the expression of cell-cycle regulators, which include cyclin E and cyclin A proteins. The molecular mechanisms of action were correlated to the blockade of the STAT3 and Akt signaling cascades. Strikingly, a high dosage of DC prompted a self-protection action through inducing cell-dependent autophagy in HCT-116 cells. Suppression of autophagy induced cell death in the treatment of DC in HCT-116 cells. DC seemed to inhibit cell proliferation of CRC differentially, and the therapeutic advantage appeared to be autophagy dependent. Moreover, consumption of DC blocked the tumor growth of colorectal adenocarcinoma in an experimental animal model. In conclusion, our results suggested that DC could act as a therapeutic agent through the significant suppression of tumor growth of human CRC cells.


Assuntos
Antineoplásicos/administração & dosagem , Ácidos Cafeicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Autofagia , Ácidos Cafeicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Ciclina A/metabolismo , Ciclina E/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Células HT29 , Humanos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Ecotoxicol Environ Saf ; 197: 110610, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32298858

RESUMO

Cadmium pollution and poisoning are serious environmental and pharmacological concerns, and effective drugs can alleviate or offset cadmium-induced toxicity are badly needed. In this study, Caffeic acid phenethyl ester (CAPE), a major active component of propolis, showed protective effect against CdCl2-induced toxicology by suppressing autophagy in HepG2 cells. CircRNAs are increasingly perceived as vital regulators in the process of autophagy. However, it remain unclear whether circRNAs are involved in CAPE's protection against CdCl2-induced autophagy. Under this context, the roles of CircRNA (hsa_circ_0040768) in CAPE's protection against CdCl2-induced damage were investigated by PCR and Western blot. Results showed that CAPE significantly (P < 0.05) increased cell viability via inhibiting CdCl2-induced autophagy, and this process was regulated by hsa_circ_0040768/MAP1LC3B axis. Overexpressing hsa_circ_0040768 led to reduced cell viability and increased autophagy in CAPE-treated HepG2 cells exposed to CdCl2. In contrast, silencing hsa_circ_0040768 showed similar protective effect to CAPE. These results show for the first time the involvement of the hsa_circ_0040768/MAP1LC3B axis in the CAPE's protection against CdCl2-induced autophagy, and provide novel insights into the pathogenesis and potential prevention/treatment of cadmium-associated diseases.


Assuntos
Autofagia/efeitos dos fármacos , Cádmio/toxicidade , Ácidos Cafeicos/farmacologia , Poluentes Ambientais/toxicidade , Álcool Feniletílico/análogos & derivados , RNA Circular/metabolismo , Autofagia/genética , Células Hep G2 , Humanos , Álcool Feniletílico/farmacologia
5.
Oxid Med Cell Longev ; 2020: 6431459, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184918

RESUMO

Oxidative stress has been recognized as the contributor to diabetic peripheral neuropathy (DPN). Antioxidant strategies have been most widely explored; nevertheless, whether antioxidants alone prevent DPN still remains inconclusive. In the present study, we established an in vitro DPN cell model for drug screening using Schwann RSC96 cells under high glucose (HG) stimulation, and we found that salvianolic acid A (SalA) mitigated HG-induced injury evidenced by cell viability and myelination. Mechanistically, SalA exhibited strong antioxidative effects by inhibiting 1,1-diphenyl-2-picrylhydrazyl (DPPH) and reducing reactive oxygen species (ROS), malondialdehyde (MDA), and oxidized glutathione (GSSG) content, as well as upregulating antioxidative enzyme mRNA expression. In addition, SalA significantly extenuated neuroinflammation with downregulated inflammatory factor mRNA expression. Furthermore, SalA improved the mitochondrial function of HG-injured Schwann cells by scavenging mitochondrial ROS, decreasing mitochondrial membrane potential (MMP), and enhancing ATP production, as well as upregulating oxidative phosphorylation gene expression. More importantly, we identified nuclear factor-E2-related factor 2 (Nrf2) as the upstream regulator which mediated protective effects of SalA on DPN. SalA directly bound to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) and thus disrupted the interaction of Nrf2 and Keap1 predicted by LibDock of Discovery Studio. Additionally, SalA significantly inhibited Nrf2 promoter activity and downregulated Nrf2 mRNA expression but without affecting Nrf2 protein expression. Interestingly, SalA upregulated the nuclear Nrf2 expression and promoted Nrf2 nuclear translocation by high content screening assay, which was confirmed to be involved in its antiglucotoxicity effect by the knockdown of Nrf2 in RSC96 cells. In KK-Ay mice, we demonstrated that SalA could effectively improve the abnormal glucose and lipid metabolism and significantly protect against DPN by increasing the mechanical withdrawal threshold and sciatic nerve conduction velocity and restoring the ultrastructural impairment of the injured sciatic nerve induced by diabetes. Hence, SalA protected against DPN by antioxidative stress, attenuating neuroinflammation, and improving mitochondrial function via Nrf2. SalA may be prospective therapeutics for treating DPN.


Assuntos
Ácidos Cafeicos/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/metabolismo , Lactatos/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/metabolismo , Animais , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Linhagem Celular , Neuropatias Diabéticas/patologia , Glucose/toxicidade , Inflamação/patologia , Lactatos/química , Lactatos/farmacologia , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/patologia , Ratos , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Nervo Isquiático/ultraestrutura
6.
Life Sci ; 247: 117439, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32070709

RESUMO

AIM: This study was aimed to synthesize novel caffeic acid derivatives and evaluate their potential applications for the treatment of oxidative stress associated disease. MAIN METHODS: Caffeic acid sulfonamide derivatives were synthesized by coupling sulfonamides to the backbone of caffeic acid and fully characterized by melting point test, FT-IR, MS, NMR, UV-vis and n-octanol-water distribution assay. Their free radical scavenging ability was evaluated using DPPH assay and cytotoxicity against A549 cells were determined by MTT assay. The protective effect of these derivatives against hydrogen peroxide (H2O2) induced oxidative injury was assessed in A549 cells from cell viability, production of reactive oxygen species (ROS) and malondialdehyde (MDA), alternation of antioxidase activities, and expressions of Nrf2 and its target genes. KEY FINDINGS: Six novel caffeic acid sulfonamide derivatives were obtained. The derivatives showed better liphophilicity than the parent caffeic acid. CASMZ, CAST and CASQ exhibited similar DPPH scavenging capability as caffeic acid, while the protection of hydroxyl groups on the benzene ring with acetyl groups caused decrease in radical scavenging activity. No inhibitory effect on the proliferation of A549 cells were observed up to a concentration of 50 µM. Pre-treatment of cells with these derivatives strongly inhibited H2O2 induced decrease of cell viability, reduced the production of ROS and MDA, promoted antioxidase activities, and further upregulated the expression of Nrf2 and its target genes. SIGNIFICANCE: Caffeic acid sulfonamide derivatives were synthesized with simple reactions under mild conditions. They might protect cells from H2O2-induced oxidative injury via Nrf2 pathway.


Assuntos
Antioxidantes/síntese química , Ácidos Cafeicos/síntese química , Ácidos Cafeicos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/síntese química , Células A549 , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Descoberta de Drogas/métodos , Radicais Livres/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Estrutura Molecular , Oxirredução , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
7.
Int. j. morphol ; 38(1): 135-139, Feb. 2020. graf
Artigo em Espanhol | LILACS | ID: biblio-1056411

RESUMO

La angiogénesis es el proceso por el cual se forman nuevos vasos sanguíneos a partir de otros ya existentes. Para que esto se lleve a cabo de forma correcta debe existir un balance entre los factores proangiogénicos y los factores antiangiogénicos dentro del microambiente tisular. Por otra parte, la existencia de productos químicos naturales como los polifenoles, que son capaces de adquirirse en la dieta, inducen a estos factores a intervenir en el proceso de angiogénesis. Se administraron los polifenoles en filtros de metilcelulosa sobre la membrana alantocoriónica de huevos White Leghorn, manteniendo el posterior desarrollo normal del feto. Se utilizaron 15 fetos de pollo fijados en formalina tamponada, a los cuales se extrajo el corazón. El procesamiento de las muestras de corazón se realizó a través de técnicas histológicas, histoquímicas e inmunohistoquímica. Finalmente se evaluó la presencia del VEGF y la capacidad de formar vasos sanguíneos bajo el tratamiento con los polifenoles. La inmunorreactividad fue cuantificada mediante Image J®. Los resultados indican que Ácido cafeico y Pinocembrina disminuyen la densidad microvascular y la expresión de VEGF en corazones de fetos de pollo tratados con estos polifenoles. Tanto el Ácido Cafeico como la Pinocembrina cumplen un rol inhibitorio en el proceso de angiogénesis fisiológica en corazón de pollo, pudiendo modular las vías de señalización mediadas por los VEGFR o modulando la disponibilidad de VEGF. Estos polifenoles podrían utilizarse para el estudio de otros tejidos asociados a angiogénesis patológica.


Angiogenesis is the process by which new blood vessels are formed from other existing ones. A balance between proangiogenic factors and anti-angiogenic factors within the microenvironment must exist for the process to be carried out correctly. Similarly, the existence of natural chemicals such as polyphenols, which are capable of being acquired in the diet, induce these factors in the angiogenic process. Polyphenols were administered in the methylcellulose filters on the of chorioallantoic membrane of White Leghorn eggs, maintaining the normal posterior development of the fetus. 15 chicken fetuses were fixed in buffered formalin, obtaining the hearts to histological processing, performing histological, histochemical and immunohistochemical techniques. VEGF levels and the ability of the blood vessels growing under the stimulation of the polyphenols were evaluated. Immunoreactivity was quantified by Image J. The results indicate that caffeic acid and pinocembrin decreased microvascular density and VEGF expression in hearts stimulated with these polyphenols. Both the caffeic and pinocembrin acids play an inhibitory role in the physiological angiogenesis process in the chicken heart, which decrease the microvascular density and could act by modulating the signaling pathways mediated by the VEGFR or by modulating the availability of VEGF. The use of these polyphenols could be useful in studies of other tissues associated with pathological angiogenesis.


Assuntos
Animais , Ácidos Cafeicos/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Embrião de Galinha , Polifenóis/farmacologia
8.
Molecules ; 25(3)2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033066

RESUMO

The incidence of gastrointestinal cancers is increasing every year. Irinotecan (CPT-11), a drug used in the treatment of colorectal cancer and gastric cancer, is metabolized by carboxylesterases to an active metabolite, SN-38, which is more cytotoxic. CAPE (caffeic acid phenethyl ester) is an active component of propolis, which has a high antibacterial, antiviral, and antineoplastic potential. This study analyses the impact of CAPE on the cytotoxic (MTT assay), genotoxic (comet assay) and proapoptotic (caspase-3/7 activity) potential of irinotecan and its metabolite SN-38 in cultures of gastrointestinal neoplastic cells (HCT116, HT29, AGS). Cytotoxicity and genotoxicity activities of these compounds were carried out in comparison with human peripheral blood lymphocytes (PBLs) in vitro. The antioxidant potential of CAPE was investigated in relation H2O2-induced oxidative stress in the both neoplastic cells and PBLs. CAPE expressed cytotoxic, genotoxic, and pro-apoptotic activity against AGS, HCT116, and HT29 tumor cells. CAPE, in the presence of different concentrations of irinotecan or SN38, decreased the cytotoxicity, genotoxicity, and pro-apoptotic activity in these cell lines, but it has no such action on normal human peripheral blood lymphocytes.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Ácidos Cafeicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Irinotecano/farmacologia , Álcool Feniletílico/análogos & derivados , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/farmacologia , Dano ao DNA/efeitos dos fármacos , Sinergismo Farmacológico , Células HCT116 , Células HT29 , Humanos , Peróxido de Hidrogênio/toxicidade , Irinotecano/análogos & derivados , Linfócitos/efeitos dos fármacos , Mutagênicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/farmacologia , Própole/farmacologia , Inibidores da Topoisomerase I/farmacologia
9.
Molecules ; 25(2)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31936160

RESUMO

: Multidrug resistance (MDR) is a complicated ever-changing problem in cancer treatment, and P-glycoprotein (P-gp), a drug efflux pump, is regarded as the major cause. In the way of developing P-gp inhibitors, natural products such as phenolic acids have gotten a lot of attention recently. The aim of the present study was to investigate the modulating effects and mechanisms of caffeic acid on human P-gp, as well as the attenuating ability on cancer MDR. Calcein-AM, rhodamine123, and doxorubicin were used to analyze the interaction between caffeic acid and P-gp, and the ATPase activity of P-gp was evaluated as well. Resistance reversing effects were revealed by SRB and cell cycle assay. The results indicated that caffeic acid uncompetitively inhibited rhodamine123 efflux and competitively inhibited doxorubicin efflux. In terms of P-gp ATPase activity, caffeic acid exhibited stimulation in both basal and verapamil-stimulated activity. The combination of chemo drugs and caffeic acid resulted in decreased IC50 in ABCB1/Flp-InTM-293 and KB/VIN, indicating that the resistance was reversed. Results of molecular docking suggested that caffeic acid bound to P-gp through GLU74 and TRY117 residues. The present study demonstrated that caffeic acid is a promising candidate for P-gp inhibition and cancer MDR attenuation.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Ácidos Cafeicos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/química , Adenosina Trifosfatases/química , Adenosina Trifosfatases/metabolismo , Ácidos Cafeicos/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Quimioterapia Combinada , Fluoresceínas/farmacologia , Humanos , Simulação de Acoplamento Molecular , Neoplasias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rodaminas/farmacologia , Verapamil/farmacologia
10.
Nutrients ; 12(1)2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31935840

RESUMO

Cichoric acid (CA) belongs to the group of polyphenols, which occurs in a variety of plant species and it is characterized by anticancer, antibacterial, and antiviral properties. Selected polyphenols have the ability to combine with metal ions to form chelate complexes that reveal greater biological activity than free compounds. In order to study possible antimicrobial and anticancer effect of CA and its complexes with copper(II)/zinc(II)/nickel(II)/cobalt(II) we decided to conduct cytotoxicity tests to estimate the most effective concentrations of tested compounds. The results of the presented study demonstrated, for the first time, that the treatment with newly synthesized CA-metal complexes has anticancer and antimicrobial effects, which were examined in seven different cell lines: MCF-7, MDA-MB-231, and ZR-75-1 breast cancer cell lines, A375 melanoma cell line, DLD-1 cell line, LN-229 cell line, FN cell line; five bacterial strains: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, Proteus vulgaris, Lactobacillus rhamnosus, yeast Sacchcaromyces boulardii, and pathogenic yeast-like fungi Candida albicans. The presented study indicates that CA-metal complexes could be considered as a potential supplementary tool in anticancer therapy, however, because of their possible toxic activity on fibroblasts, they should be used with caution. Some of the tested complexes have also preservative properties and positive influence on normal non-pathogenic microorganisms, which was demonstrated in selected microbial strains, therefore they may serve as food preservatives of natural origin with cytoprotective properties.


Assuntos
Anti-Infecciosos/administração & dosagem , Antineoplásicos/administração & dosagem , Bactérias/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Complexos de Coordenação/administração & dosagem , Extratos Vegetais/farmacologia , Succinatos/farmacologia , Leveduras/efeitos dos fármacos , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ácidos Cafeicos/uso terapêutico , Candida albicans/efeitos dos fármacos , Linhagem Celular Tumoral , Complexos de Coordenação/efeitos adversos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Fibroblastos/efeitos dos fármacos , Humanos , Íons , Metais/farmacologia , Metais/uso terapêutico , Testes de Sensibilidade Microbiana , Neoplasias/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Saccharomyces boulardii/efeitos dos fármacos , Succinatos/uso terapêutico
11.
BMC Cardiovasc Disord ; 20(1): 15, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931718

RESUMO

BACKGROUND: Platelets in patients with type 2 diabetes mellitus (DM2) are characterized by increased activation and aggregation, which tends to be associated with a high morbidity and mortality due to cardiovascular disease (CVD). Moreover, a large proportion of DM2 patients show an inadequate response to standard antiplatelet treatments, contributing to recurrent cardiovascular events. In our previous study, we indicated that Salvianolic acid A (SAA) presents an antiplatelet effect in healthy volunteers. However, whether it can inhibit "activated platelets" with a pathologic status has not been explored. Therefore, this study was designed to investigate the antiplatelet effect of SAA and its diabetic complication-related difference in DM2. METHODS: Forty patients diagnosed with DM2 from January 2018 to April 2018 were recruited. Fibrinogen-binding (PAC-1) and P-selectin (CD62p) flow cytometry reagents were measured under resting and stimulated conditions by flow cytometry, while agonist-induced platelet aggregation was conducted by light transmission aggregometry. Before all these measurements were conducted, all platelet samples were preincubated with a vehicle or SAA for 10 min. Additionally, the diabetic complication-related difference in the antiplatelet effect of SAA was further studied in enrolled patients. RESULTS: The expressions of PAC-1 and CD62p were elevated in DM2, as well as the maximal platelet aggregation. In addition, SAA decreased the expressions of PAC-1 and CD62p, which were enhanced by ADP and thrombin (all P < 0.01). It also reduced the platelet aggregation induced by ADP (P < 0.001) and thrombin (P < 0.05). Comparing the antiplatelet effect of SAA on DM2, with and without diabetic complications, no statistically significant difference was found (all P > 0.05). CONCLUSIONS: The present study demonstrated that SAA can inhibit platelet activation and aggregation in patients with DM2, and the inhibition did not abate for the existence of diabetic complications.


Assuntos
Plaquetas/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Lactatos/farmacologia , Inibidores da Agregação de Plaquetas/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Idoso , Biomarcadores/sangue , Plaquetas/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Inibidores da Agregação de Plaquetas/efeitos adversos
12.
Nanotechnology ; 31(17): 175705, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31931488

RESUMO

Due to the resistance to drugs, studies involving the combination and controlled release of different agents are gradually increasing. In this study, two different active ingredients, known to have antibacterial and antiparasitic activities, were encapsulated into single polymeric nanoparticles. After co-encapsulation their antibacterial and antileishmanial activity was enhanced approximately 5 and 250 times, respectively. Antibacterial and antileishmanial activities of caffeic acid phenethyl ester and juglone loaded, multifunctional nanoformulations (CJ4-CJ6-CJ8) were also evaluated for the first time in the literature comparatively with their combined free formulations. The antibacterial activity of the multifunctional nanoformulation (CJ8) were found to have a much higher activity (MIC values 6.25 and 12.5 µg ml-1 for S. aureus and E. coli, respectively) than all other formulations. Similar efficacy for CJ8 was obtained in the antiparasitic study against the Leishmania promastigotes and the IC50 was reduced to 0.1263 µg ml-1. The high activity of multifunctional nanoparticles is not only due to the synergistic effect of the active molecules but also by the encapsulation into polymeric nanoparticles. Therefore, it has been shown in the literature for the first time that the biological activity of molecules whose activity is increased by the synergistic effect can be improved with nanosystems.


Assuntos
Antibacterianos/farmacologia , Antiparasitários/farmacologia , Ácidos Cafeicos/farmacologia , Naftoquinonas/farmacologia , Álcool Feniletílico/análogos & derivados , Antibacterianos/química , Antiparasitários/química , Ácidos Cafeicos/química , Escherichia coli/efeitos dos fármacos , Leishmania/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Nanopartículas , Naftoquinonas/química , Tamanho da Partícula , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Staphylococcus aureus/efeitos dos fármacos
13.
J Ethnopharmacol ; 252: 112601, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31981746

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge, as known as Danshen, has used for the prevention and treatment of cardiovascular diseases clinically and anti-cancer activities. Salvianolic acid A (SAA), one of the most abundant ingredients, hydrophilic derivatives of Salvia miltiorrhiza Bunge, exerts a variety of pharmacological actions, such as anti-oxidative, anti-inflammatory and anti-cancer activities. However, the impact of SAA on nasopharyngeal carcinoma (NPC) invasion and metastasis remains unexplored. AIM OF THE STUDY: To investigate the potential of SAA to prevent migration and invasion on NPC cell. MATERIALS AND METHODS: MTT assay and Boyden chamber assay were performed to determine cell proliferation, migration and invasion abilities, respectively. The activity and protein expression of matrix metalloproteinase-2 (MMP-2) were determined by gelatin zymography and western blotting. RESULTS: Here, we showed that SAA considerably suppressed the migrative and invasive activity of human NPC cells but not rendered cytotoxicity. In SAA-treated NPC cells, the activity and expression of matrix metalloproteinase-2 (MMP-2), a key regulator of cancer cell invasion, were reduced. Additionally, the presence of high concentrations of SAA dramatically abolished the activation of focal adhesion kinase (FAK) and moderately inhibited the phosphorylation of Src and ERK in NPC cells. CONCLUSIONS: Our results demonstrated that SAA inhibited the migration and invasion of NPC cells, accompanied by downregulation of MMP-2 and inactivation of FAK, Src, and ERK pathways. These findings indicate a usefulness of SAA on restraining NPC invasion and metastasis.


Assuntos
Antineoplásicos/farmacologia , Ácidos Cafeicos/farmacologia , Lactatos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Metaloproteinases de Matriz/farmacologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Invasividade Neoplásica
14.
Food Chem ; 310: 125823, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31757489

RESUMO

Phenolic acids, which are important aromatic secondary metabolites, are widely distributed in plant foods. In this study, a simple, economical and fast on-line immobilized trypsin microreactor was developed for evaluating the inhibitory activity of phenolic acids by capillary electrophoresis. The Michaelis-Menten constant (Km) of immobilized trypsin was determined as 0.99 mM, and the half-maximal inhibitory concentration (IC50) and inhibition constant (Ki) of benzamidine were measured as 3.39 and 1.68 mM, respectively. Then, the developed strategy was applied to investigate the inhibitory activity of six phenolic acids on trypsin. The results showed that gallic acid, caffeic acid and ferulic acid had high inhibitory activity at concentration of 150 µM. Molecular docking results illustrated that gallic acid, caffeic acid and ferulic acid can interact indirectly with the catalytic and substrate-binding sites of trypsin. The developed strategy is an effective tool for evaluating inhibitory activity of phenolic acids on trypsin.


Assuntos
Eletroforese Capilar/instrumentação , Enzimas Imobilizadas/metabolismo , Hidroxibenzoatos/metabolismo , Inibidores da Tripsina/farmacologia , Tripsina/metabolismo , Sítios de Ligação , Reatores Biológicos , Ácidos Cafeicos/química , Ácidos Cafeicos/metabolismo , Ácidos Cafeicos/farmacologia , Ácidos Cumáricos/química , Ácidos Cumáricos/metabolismo , Ácidos Cumáricos/farmacologia , Eletroforese Capilar/métodos , Enzimas Imobilizadas/química , Ácido Gálico/química , Ácido Gálico/metabolismo , Ácido Gálico/farmacologia , Hidroxibenzoatos/farmacologia , Simulação de Acoplamento Molecular , Tripsina/química , Inibidores da Tripsina/metabolismo
15.
Int J Mol Sci ; 20(24)2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31842335

RESUMO

In recent years, hypersensitivity reactions to the Shuanghuanglian injection have attracted broad attention. However, the componential chief culprits inducing the reactions and the underlying mechanisms involved have not been completely defined. In this study, we used a combination of approaches based on the mouse model, human umbilical vein endothelial cell monolayer, real-time cellular monitoring, immunoblot analysis, pharmacological inhibition, and molecular docking. We demonstrated that forsythoside A and forsythoside B contributed to Shuanghuanglian injection-induced pseudoallergic reactions through activation of the RhoA/ROCK signaling pathway. Forsythoside A and forsythoside B could trigger dose-dependent vascular leakage in mice. Moreover, forsythoside A and forsythoside B slightly elicited mast cell degranulation. Correspondingly, treatment with forsythoside A and forsythoside B disrupted the endothelial barrier and augmented the expression of GTP-RhoA, p-MYPT1, and p-MLC2 in a concentration-dependent manner. Additionally, the ROCK inhibitor effectively alleviated forsythoside A/forsythoside B-induced hyperpermeability in both the endothelial cells and mice. Similar responses were not observed in the forsythoside E-treated animals and cells. These differences may be related to the potential of the tested compounds to react with RhoA-GTPγS and form stable interactions. This study innovatively revealed that some forsythosides may cause vascular leakage, and therefore, limiting their contents in injections should be considered.


Assuntos
Ácidos Cafeicos/farmacologia , Medicamentos de Ervas Chinesas/química , Glucosídeos/farmacologia , Glicosídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Ácidos Cafeicos/química , Permeabilidade Capilar/efeitos dos fármacos , Permeabilidade Capilar/imunologia , Degranulação Celular , Medicamentos de Ervas Chinesas/administração & dosagem , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Glucosídeos/química , Glicosídeos/química , Humanos , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Quinases Associadas a rho/química , Proteína rhoA de Ligação ao GTP/química
16.
Int J Mol Sci ; 20(22)2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31726654

RESUMO

Breast cancer is the current leading cause of cancer death in females worldwide. Although current chemotherapeutic drugs effectively reduce the progression of breast cancer, most of these drugs have many unwanted side effects. Salvianolic acid B (Sal-B) is a bioactive compound isolated from the root of Danshen Radix with potent antioxidant and anti-inflammatory properties. Since free radicals play a key role in the initiation and progression of tumor cells growth and enhance their metastatic potential, the current study was designed to investigate the antitumor activity of Sal-B and compare it with the antitumor activity of the traditional anticancer drug, cisplatin. In vitro, Sal-B decreased the human breast cancer adenocarcinoma (MCF-7) cells proliferation in a concentration and time dependent manner. In vivo and similar to cisplatin treatment, Sal-B significantly reduced tumor volume and increased the median survival when compared to tumor positive control mice group injected with Ehrlich solid carcinoma cell line (ESC). Sal-B decreased plasma level of malondialdehyde as a marker of oxidative stress and increased plasma level of reduced glutathione (GSH) as a marker of antioxidant defense when compared to control ESC injected mice. Either Sal-B or cisplatin treatment decreased tumor tissue levels of tumor necrosis factor (TNF-α), matrix metalloproteinase-8 (MMP-8), and Cyclin D1 in ESC treated mice. Contrary to cisplatin treatment, Sal-B did not decrease tumor tissue Ki-67 protein in ESC injected mice. Immunohistochemical analysis revealed that Sal-B or cisplatin treatment increased the expression of the apoptotic markers caspase-3 and P53. Although Sal-B or cisplatin significantly reduced the expression of the angiogenic factor vascular endothelial growth factor (VEGF) in ESC injected mice, only Sal-B reduced expression level of COX-2 in ESC injected mice. Our data suggest that Sal-B exhibits antitumor features against breast cancer cells possibly via enhancing apoptosis and reducing oxidative stress, inflammation, and angiogenesis.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama , Ácidos Cafeicos/farmacologia , Carcinoma de Ehrlich , Lactatos/farmacologia , Neovascularização Patológica , Estresse Oxidativo/efeitos dos fármacos , Animais , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma de Ehrlich/irrigação sanguínea , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Células MCF-7 , Camundongos , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
ACS Appl Mater Interfaces ; 11(43): 39613-39623, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31613607

RESUMO

Bifunctional Au-Fe3O4 nanoheterodimers were synthesized by thermally decomposing Fe(III)oleate on gold nanoparticles followed by functionalizing with tiron, 2,3-dihydroxybenzoic acid, or caffeic acid. These catechol derivatives are antioxidative and thus are predicted to function as superoxide scavengers. In particular, caffeic acid lost its antioxidant capacity, although it was covalently linked through its carboxyl moiety to the Fe3O4 surface. Tiron was shown to bind via its catechol group to the Au-Fe3O4 nanoheterodimers, and 2,3-dihydroxybenzoic was just physisorbed between the oleic acid surface structures. Caffeic-acid stabilized Au-Fe3O4 nanoheterodimers turned out to act as X-ray protector in healthy cells but as X-ray enhancing agents in cancer cells. Furthermore, these functionalized Au-Fe3O4 nanoheterodimers were found to inhibit the migratory capacity of the cancer cells.


Assuntos
Ácidos Cafeicos , Óxido Ferroso-Férrico , Depuradores de Radicais Livres , Ouro , Nanoestruturas , Neoplasias , Protetores contra Radiação , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Óxido Ferroso-Férrico/química , Óxido Ferroso-Férrico/farmacologia , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Ouro/química , Ouro/farmacologia , Humanos , Células MCF-7 , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/radioterapia , Protetores contra Radiação/química , Protetores contra Radiação/farmacologia , Raios X
18.
Chem Biodivers ; 16(12): e1900405, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31566891

RESUMO

The purpose of this study was to examine the neuroprotective effects of caffeic acid hexyl (CAF6) and dodecyl (CAF12) amide derivatives on the early stage of retinopathy in streptozotocin-induced diabetic rats. Animals were divided in five groups (n=8/group); one group consisted of non-diabetic rats as control, while the other four were diabetic animals either non-treated or treated with CAF6, CAF12 or resveratrol intravitreally for four weeks. Retinal superoxide dismutase (SOD) activity and 8-iso-prostaglandin F2α (iPF2α ) levels were evaluated by an ELISA assay. Phosphorylation of ERK1/2 and AKT was determined by immunoblotting in retinal homogenates. Retinal morphology was also examined using light microscopy. Treatment with CAF6 and CAF12 increased retinal SOD activity, while it decreased iPF2α levels in diabetic rats. Phosphorylation of ERK1/2 was increased, while AKT phosphorylation was decreased in diabetic rats compared to normal control and these alterations were significantly reversed in diabetic rats treated with CAF6 and CAF12. Furthermore, thickness of the whole retinal layer, outer nuclear layer, and ganglion cell count were decreased in diabetic rats compared to control and CAF6 and CAF12 treatments prevented these changes. CAF6 and CAF12 seem to be effective agents for treatment of diabetic retinopathy via attenuation of retinal oxidative stress and improvement of neuronal survival signaling.


Assuntos
Ácidos Cafeicos/química , Retinopatia Diabética/patologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Retinopatia Diabética/etiologia , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Retina/metabolismo , Retina/patologia , Superóxido Dismutase/metabolismo
19.
Int J Biol Sci ; 15(10): 2256-2264, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31592132

RESUMO

Nature has generously offered life-saving therapies to mankind by providing evolutionarily optimized drug-like entities in the form of natural products. These splendid gifts of nature have served as most suitable candidates for anti-cancer drug discovery due to their pleiotropic activity on target molecules. This review aims to provide an update on the natural sources and bioactivities of such gifts from nature, salvianolic acid A & B, which are major bioactive constituents of a traditional Chinses medicinal herb, Salvia miltiorrhiza. Salvianolic acid A & B have been reported to owe anti-cancer, anti-inflammatory and cardioprotective activities. Currently salvianolic acids have been emerged as potent anti-cancer molecules. Salvianolic acid A & B fight cancer progression by prompting apoptosis, halting cell cycle and adjourning metastasis by targeting multiple deregulated signaling networks of cancer. Moreover, salvianolic acid A & B display potency towards sensitizing cancer cells to chemo-drugs. The review purposes that salvianolic acid A & B supply a novel opportunity for drug discovery but further experimentation is mandatory to embellish the knowledge of their pharmacological usage and to access their toxicological limits in order to establish these compounds as potential multitarget future drugs.


Assuntos
Benzofuranos/farmacologia , Ácidos Cafeicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Lactatos/farmacologia , Polifenóis/farmacologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Humanos , Transdução de Sinais/efeitos dos fármacos
20.
Tissue Cell ; 60: 14-20, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31582013

RESUMO

A number of studies have indicated the benefits of coffee consumption on physical and mental health; however, scientific evidence on these effects, in particular of the benefits to brain function, has not been determined. In the present study, we aimed to determine the benefits of caffeic acid in the nervous system. For this purpose, we administered doses of 0 or 300 mg/kg for 30 days to mice that were not otherwise affected. We analyzed survival of newly born cells, oxidative stress, inflammatory marker expression, and microglial activation in the hippocampus. We found that caffeic acid had no effect on the expression levels of neurotrophic factors and inflammatory or anti-inflammatory cytokines. However, caffeic acid-treated mice exhibited significantly lower levels of 4-hydroxynonenal, an oxidative stress marker, in the hippocampus, as well as significantly fewer activated microglia. Abnormally high oxidative stress, as well as activated microglia accumulation are both considered to relate to the pathophysiology of neurological and psychiatric disorders. The present study demonstrates the physiological effects of caffeic acid and may explain the suggested benefits of coffee consumption on brain health.


Assuntos
Antioxidantes/farmacologia , Ácidos Cafeicos/farmacologia , Hipocampo/efeitos dos fármacos , Microglia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Hipocampo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Neurogênese/efeitos dos fármacos
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