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1.
Chem Pharm Bull (Tokyo) ; 67(9): 966-976, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31257308

RESUMO

Honokiol, a biphenolic neolignan isolated from Magnolia officinalis, was reported to have a promising anti-inflammatory activity for the treatment of various diseases. There are many efforts on the synthesis and structure-activity relationship of honokiol derivatives. However, regioselective O-alkylation of honokiol remains a challenge and serves as a tool to provide not only some derivatives but also chemical probes for target identification and mode of action. In this study, we examined the reaction condition for regioselective O-alkylation, in which C2 and C4'-alkylated analogs of honokiol were synthesized and evaluated for inhibitory activity on nitric oxide production and cyclooxygenase-2 expression. Furthermore, we successfully synthesized a potential photoaffinity probe consisting of biotin and benzophenone based on a C4'-alkylated derivative.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Compostos de Bifenilo/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inflamação/tratamento farmacológico , Lignanas/farmacologia , Alquilação , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Compostos de Bifenilo/síntese química , Compostos de Bifenilo/química , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Humanos , Inflamação/metabolismo , Lignanas/síntese química , Lignanas/química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Estereoisomerismo
2.
J Enzyme Inhib Med Chem ; 34(1): 1368-1372, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31347930

RESUMO

To develop multifunctional aldose reductase (AKR1B1) inhibitors for anti-diabetic complications, a novel series of 2-phenoxypyrido[3,2-b]pyrazin-3(4H)-one derivatives were designed and synthesised. Most of the derivatives were found to be potent and selective against AKR1B1, and 2-(7-chloro-2-(3,5-dihydroxyphenoxy)-3-oxopyrido[3,2-b]pyrazin-4(3H)-yl) acetic acid (4k) was the most active with an IC50 value of 0.023 µM. Moreover, it was encouraging to find that some derivatives showed strong antioxidant activity, and among them, the phenolic 3,5-dihydroxyl compound 4l with 7-bromo in the core structure was proved to be the most potent, even comparable to that of the well-known antioxidant Trolox. Thus the results suggested success in the construction of potent and selective AKR1B1 inhibitors with antioxidant activity.


Assuntos
Aldeído Redutase/antagonistas & inibidores , Antioxidantes/farmacologia , Desenho de Drogas , Inibidores Enzimáticos/farmacologia , Hipoglicemiantes/farmacologia , Pirazinas/farmacologia , Antioxidantes/química , Compostos de Bifenilo/química , Inibidores Enzimáticos/química , Hipoglicemiantes/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Picratos/química , Pirazinas/química , Relação Estrutura-Atividade
3.
Chem Biol Interact ; 308: 339-349, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170387

RESUMO

Magnolol, the most abundant bioactive constituent of the Chinese herb Magnolia officinalis, has been found with multiple biological activities, including anti-oxidative, anti-inflammatory and enzyme-regulatory activities. In this study, the inhibitory effects and inhibition mechanism of magnolol on human carboxylesterases (hCEs), the key enzymes responsible for the hydrolytic metabolism of a variety of endogenous esters as well as ester-bearing drugs, have been well-investigated. The results demonstrate that magnolol strongly inhibits hCE1-mediated hydrolysis of various substrates, whereas the inhibition of hCE2 by magnolol is substrate-dependent, ranging from strong to moderate. Inhibition of intracellular hCE1 and hCE2 by magnolol was also investigated in living HepG2 cells, and the results showed that magnolol could strongly inhibit intracellular hCE1, while the inhibition of intracellular hCE2 was weak. Inhibition kinetic analyses and docking simulations revealed that magnolol inhibited both hCE1 and hCE2 in a mixed manner, which could be partially attributed to its binding at two distinct ligand-binding sites in each carboxylesterase, including the catalytic cavity and the regulatory domain. In addition, the potential risk of the metabolic interactions of magnolol via hCE1 inhibition was predicted on the basis of a series of available pharmacokinetic data and the inhibition constants. All these findings are very helpful in deciphering the metabolic interactions between magnolol and hCEs, and also very useful for avoiding deleterious interactions via inhibition of hCEs.


Assuntos
Compostos de Bifenilo/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Lignanas/metabolismo , Sítios de Ligação , Biocatálise , Compostos de Bifenilo/química , Hidrolases de Éster Carboxílico/antagonistas & inibidores , Domínio Catalítico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Células Hep G2 , Humanos , Hidrólise , Cinética , Lignanas/química , Simulação de Acoplamento Molecular
4.
J Agric Food Chem ; 67(26): 7526-7529, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31184887

RESUMO

A limitation of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability (DRSA) due to the presence of pigments and colors in the extracts of plant-based foods was addressed. The pigments present in the test samples absorb in the same wavelength region as the DPPH radicals; this interferes with the elaborate absorbance readings of the DPPH radicals. In this contribution, electron paramagnetic resonance (EPR) spectroscopy for DPPH assay is proposed in order to avoid this limitation. In the EPR-DPPH assay, the underestimation of the radical scavenging abilities of four different pigment-containing extracts was corrected and this reflected up to a 16.1% change compared to the original values. Thus, the EPR-DPPH assay eliminated interference from the pigments coexisting in the reaction medium and improved the accuracy of the DPPH radical scavenging potential of such extracts. The principle of the proposed solution might also be employed in other assays which suffer from pigment interference.


Assuntos
Compostos de Bifenilo/química , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Depuradores de Radicais Livres/química , Picratos/química , Pigmentos Biológicos/química , Extratos Vegetais/química , Beta vulgaris/química , Capsicum/química , Cor , Rubus/química
5.
Food Chem ; 293: 285-290, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151613

RESUMO

Exogenous adenosine triphosphate (ATP) treatment at 0, 250, 500, 750, and 1000 µM retarded cap browning in mushrooms by 0, 34, 26, 51 and 32 %, respectively, during storage at 4 °C for 18 days. Triggering signaling H2O2 accumulation arising from elevating NADPH oxidase enzyme activity during 6 days of storage at 4 °C may be pivotal for promoting shikimate dehydrogenase enzyme activity in mushrooms treated with ATP during 18 days of storage at 4 °C. Promoting melatonin accumulation (390 µg kg-1 FW vs. 160 µg kg-1 FW) in mushrooms treated with ATP during cold storage may attribute to signaling H2O2 accumulation. Higher DPPH scavenging capacity (72 % vs. 65 %) in mushrooms treated with ATP may attribute to higher phenols accumulation arising from higher phenylalanine ammonialyase/polyphenol oxidase enzymes activity concomitant with higher alternative oxidase gene expression during 18 days of storage at 4 °C.


Assuntos
Trifosfato de Adenosina/farmacologia , Agaricus/efeitos dos fármacos , Temperatura Baixa , Armazenamento de Alimentos , Reação de Maillard , Trifosfato de Adenosina/administração & dosagem , Agaricus/enzimologia , Agaricus/fisiologia , Oxirredutases do Álcool/metabolismo , Compostos de Bifenilo/química , Relação Dose-Resposta a Droga , Peróxido de Hidrogênio/metabolismo , Melatonina/metabolismo , Proteínas Mitocondriais/genética , NADPH Oxidases/metabolismo , Oxirredutases/genética , Fenóis/metabolismo , Picratos/química , Proteínas de Plantas/genética , Transdução de Sinais
6.
Curr Top Med Chem ; 19(11): 914-926, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31072293

RESUMO

BACKGROUND: PIM-1 is a kinase which has been related to the oncogenic processes like cell survival, proliferation, and multidrug resistance (MDR). This kinase is known for its ability to phosphorylate the main extrusion pump (ABCB1) related to the MDR phenotype. OBJECTIVE: In the present work, we tested a new mechanistic insight on the AZD1208 (PIM-1 specific inhibitor) under interaction with chemotherapy agents such as Daunorubicin (DNR) and Vincristine (VCR). MATERIALS AND METHODS: In order to verify a potential cytotoxic effect based on pharmacological synergism, two MDR cell lines were used: Lucena (resistant to VCR) and FEPS (resistant to DNR), both derived from the K562 non-MDR cell line, by MTT analyses. The activity of Pgp was ascertained by measuring accumulation and the directional flux of Rh123. Furthermore, we performed a molecular docking simulation to delve into the molecular mechanism of PIM-1 alone, and combined with chemotherapeutic agents (VCR and DNR). RESULTS: Our in vitro results have shown that AZD1208 alone decreases cell viability of MDR cells. However, co-exposure of AZD1208 and DNR or VCR reverses this effect. When we analyzed the ABCB1 activity AZD1208 alone was not able to affect the pump extrusion. Differently, co-exposure of AZD1208 and DNR or VCR impaired ABCB1 activity, which could be explained by compensatory expression of abcb1 or other extrusion pumps not analyzed here. Docking analysis showed that AZD1208 is capable of performing hydrophobic interactions with PIM-1 ATP- binding-site residues with stronger interaction-based negative free energy (FEB, kcal/mol) than the ATP itself, mimicking an ATP-competitive inhibitory pattern of interaction. On the same way, VCR and DNR may theoretically interact at the same biophysical environment of AZD1208 and also compete with ATP by the PIM-1 active site. These evidences suggest that AZD1208 may induce pharmacodynamic interaction with VCR and DNR, weakening its cytotoxic potential in the ATP-binding site from PIM-1 observed in the in vitro experiments. CONCLUSION: Finally, the current results could have a pre-clinical relevance potential in the rational polypharmacology strategies to prevent multiple-drugs resistance in human leukemia cancer therapy.


Assuntos
Compostos de Bifenilo/farmacologia , Resistência a Múltiplos Medicamentos , Leucemia Eritroblástica Aguda/tratamento farmacológico , Leucemia Eritroblástica Aguda/enzimologia , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-pim-1/antagonistas & inibidores , Tiazolidinas/farmacologia , Compostos de Bifenilo/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Leucemia Eritroblástica Aguda/patologia , Conformação Molecular , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Tiazolidinas/química , Células Tumorais Cultivadas
7.
Chem Biol Interact ; 307: 82-90, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31047918

RESUMO

Honokiol (HKL) is a natural low-molecular-weight biphenolic compound derived from the bark of magnolia trees. Previous studies indicate that HKL exerts potent cardioprotective effects on ischemia/reperfusion (I/R) injury; however, evidence of the further relationship between HKL posttreatment and myocardial I/R injury has not been clearly found. In our study, we explored the protective effect of HKL post treatment on myocardial I/R injury in C57BL/6 mice. We also demonstrated that HKL significantly reduced cellular reactive oxygen species production and attenuated mitochondrial damage in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation (H/R). In addition, HKL was found to enhance autophagy during I/R or H/R; these effects could be partially blocked by the autophagic flux inhibitor chloroquine. Moreover, our results suggested that enhanced autophagic flux is associated with the Akt signaling pathway. Collectively, our results indicate that HKL posttreatment alleviates myocardial I/R injury and suggest a critical cardioprotective role of HKL in promoting autophagic flux.


Assuntos
Autofagia , Compostos de Bifenilo/uso terapêutico , Lignanas/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Cloroquina/farmacologia , Modelos Animais de Doenças , Lignanas/química , Lignanas/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos
8.
Molecules ; 24(8)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003408

RESUMO

The inhibitory effects of baijiu vinasse extract and its phenolic acid compounds on the Nε-carboxymethyllysine (CML) formation from dairy food were investigated. The inhibitory effect of the baijiu vinasse extract against CML formation was 43.2% in the casein and D-glucose model, which used 6 mL of the 70% acetone extract at 60 °C for 40 min. The HPLC-MS/MS profiles of the vinasse extract indicated that vanillic, chlorogenic, p-coumaric, sinapic, caffeic, ferulic, and syringic acids were seven major phenolic acid compounds. Furthermore, the inhibitory mechanism of the phenolic acid compounds in the model of dairy food was discussed by the trapping and scavenging of glyoxal. The results of this study exhibit that seven major antioxidant phenolic acid compounds may play important roles in the antioxidant activity and CML inhibition of the vinasse extract in a model of dairy foods.


Assuntos
Laticínios/análise , Depuradores de Radicais Livres/análise , Glioxal/química , Lisina/análogos & derivados , Resíduos/análise , Vinho , Antioxidantes/análise , Compostos de Bifenilo/química , Lisina/química , Fenóis/análise , Picratos/química
9.
Mater Sci Eng C Mater Biol Appl ; 101: 204-216, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029313

RESUMO

We synthesized silver nanoparticles using thirty Chinese plant extracts via a green synthetic strategy. UV-visible spectra showed that the silver nanoparticles have an absorbance at 450 nm. Among the thirty extracts, seven extracts (Cratoxylum formosum, Phoebe lanceolata, Scurrula parasitica, Ceratostigma minus, Mucuna birdwoodiana, Myrsine africana and Lindera strychnifolia) exhibited the successful synthesis of silver nanoparticles. These seven extracts showed higher 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and reducing power than the other extracts. The silver nanoparticles synthesized using these seven extracts were mostly spherical with high colloidal stability. The cytotoxicity of these seven silver nanoparticle samples on human lung cancer cells (A549) was clearly higher than that of the extracts alone. Furthermore, the cytotoxicity was affected by the presence or absence of fetal bovine serum. Moreover, the cytotoxicity of the silver nanoparticles synthesized with Cratoxylum formosum and Mucuna birdwoodiana extracts resulted in apoptotic cell death in A549 cells. The wound healing activity observed by the cell scratch method on mouse fibroblast cells (NIH3T3) suggested that the Lindera strychnifolia extract produced silver nanoparticles with decent activity. These results provide ample and systematic information for researchers on the green synthesis of silver nanoparticles using plant extracts.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Química Verde/métodos , Nanopartículas Metálicas/química , Extratos Vegetais/farmacologia , Prata/farmacologia , Cicatrização/efeitos dos fármacos , Células A549 , Animais , Compostos de Bifenilo/química , Coloides/química , Depuradores de Radicais Livres/química , Humanos , Hidrodinâmica , Nanopartículas Metálicas/ultraestrutura , Camundongos , Células NIH 3T3 , Oxirredução , Tamanho da Partícula , Picratos/química , Espectrofotometria Ultravioleta , Coloração e Rotulagem , Eletricidade Estática
10.
Molecules ; 24(7)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30978915

RESUMO

Red-flesh apples are known as functional fruits because of their rich anthocyanin. The anthocyanin content of the red flesh apple cultivar 'QN-5' we bred can reach 361 mg·kg-1 (FW), and showed higher scavenging capacity to DPPH radicals, hydroxyl radicals, and superoxide anion radicals, with scavenging rates of 80.0%, 54.0%, and 43.3%, respectively. We used this particular anthocyanin-rich 'QN-5' apple as material to examine how nanocrystallization affects the antixodiant effect of anthocyanin. The anthocyanin extract was encapsulated with biocompatible zein to form zein-anthocyanin nanoparticles (ZANPs). Transmission electron microscopy (TEM) scanning showed that ZANPs had a regular spherical shape with an average diameter size of 50-60nm. When the ratio of the zein and the anthocyanin was 1:0.5, the results suggested that the encapsulation efficiency (EE) of the ZANPs could reach as high as 92.8%, and that scavenging rate for DPPH radicals was increased from 87.1% to 97.2% compared to the non-nanocrystallized anthocyanin extract. Interestingly, treatment under alkaline conditions (pH 9.0), high temperature (90 °C), and a storage time of 7 days could decrease the scavenging capacity of the ZANPs for DPPH radicals, but this scavenging capacity loss for ZANPs was significantly lower than that observed in the non-nanocrystallized anthocyanin, suggesting the higher stability of ZANPs is caused by encapsulation. These results would provide a theoretical basis for the application of the anthocyanin in scavenging free radicals under stress conditions.


Assuntos
Antocianinas/química , Antioxidantes/química , Malus/química , Extratos Vegetais/química , Antocianinas/farmacologia , Antioxidantes/farmacologia , Compostos de Bifenilo/química , Depuradores de Radicais Livres/química , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Picratos/química , Extratos Vegetais/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Zeína/química
11.
Molecules ; 24(7)2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30959818

RESUMO

The DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay is an easy and efficient method commonly used to determine the antioxidant capacity of many food matrices and beverages. In contrast with red wines, white wines are poorer in antioxidant polyphenolics, and the more hydrophilic sulfur-containing compounds in them may contribute significantly to their antioxidant capacity. The modification of the classical DPPH method, with a methanol-buffer and the measure of EC20 (quantity of sample needed to decrease the initial DPPH concentration by 20%) has shown that sulfur-containing compounds such as cysteine (0.037 ± 0.003), glutathione (0.054 ± 0.003) or methanethiol (0.104 ± 0.003) appeared to bear antioxidant capacity comparable to well known phenolic compounds, such as catechin (0.035 ± 0.003), caffeic acid (0.057 ± 0.003) and ferulic acid (0.108 ± 0.003), respectively. In the case of white wines, the comparison with REDOX-sensory scores showed that results from this modified DPPH assay are strongly correlated with sensory attributes (r = 0.73, p < 0.1). These results provide an unprecedented illustration of the important contribution of these sulfur-containing compounds to the radical quenching ability of white wines.


Assuntos
Antioxidantes/química , Compostos de Bifenilo/química , Ensaios de Triagem em Larga Escala/métodos , Picratos/química , Vinho/análise , Ácidos Cafeicos/química , Catequina/química , Ácidos Cumáricos/química , Humanos , Fenóis/química , Compostos de Enxofre/química
12.
J Dairy Sci ; 102(7): 5922-5932, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31030915

RESUMO

Exopolysaccharide (EPS) of Lactobacillus plantarum WLPL04 and its sulfated EPS were systematically investigated for their antioxidant activities and effects on protecting the oxidative damage of Caco-2 cells from H2O2. Exopolysaccharide was successfully sulfonated from purified EPS as confirmed by Fourier-transform infrared spectroscopy, and the degree of sulfonation was 0.30. Both EPS and sulfated EPS showed antioxidant activities in vitro determined by 1,1-diphenyl-2-picrylhydrazyl, superoxide, and hydroxyl radical scavenging tests, and those activities of sulfated EPS were significantly enhanced at 1,000 µg/mL. Cell viabilities of Caco-2 in the range of 1 to 100 µg/mL of EPS and sulfated EPS showed no significant difference. In H2O2-damaged Caco-2 cells models, EPS and sulfated EPS significantly inhibited the enhancement of reactive oxygen species and malondialdehyde levels, and sulfated EPS enhanced the effects by 40.86% and 61.11% when compared with the purified EPS at the same concentration of 100 µg/mL, respectively. For the activities of antioxidant-related enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and expression of genes (SOD2, GPX2, MT1M) on Caco-2 cells, strong protection abilities against the oxidative stress were displayed from both EPS and sulfated EPS, and sulfated EPS exhibited significant enhancement as compared with either EPS or control groups. In summary, sulfonation is an effective strategy for improving the antioxidant activities of EPS from L. plantarum WLPL04 in vitro and on Caco-2 cells.


Assuntos
Antioxidantes/farmacologia , Lactobacillus plantarum/química , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos Bacterianos/farmacologia , Substâncias Protetoras/farmacologia , Antioxidantes/química , Compostos de Bifenilo/química , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Humanos , Radical Hidroxila/química , Mucosa Intestinal/efeitos dos fármacos , Lactobacillus plantarum/isolamento & purificação , Picratos/química , Polissacarídeos Bacterianos/química , Substâncias Protetoras/química , Superóxidos/química
13.
Oxid Med Cell Longev ; 2019: 3640753, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019651

RESUMO

Among a series of xanthones identified from mangosteen, the fruit of Garcinia mangostana L. (Guttifereae), α- and γ-mangostins are known to be major constituents exhibiting diverse biological activities. However, the effects of γ-mangostin on oxidative neurotoxicity and impaired memory are yet to be elucidated. In the present study, the protective effect of γ-mangostin on oxidative stress-induced neuronal cell death and its underlying action mechanism(s) were investigated and compared to that of α-mangostin using primary cultured rat cortical cells. In addition, the effect of orally administered γ-mangostin on scopolamine-induced memory impairment was evaluated in mice. We found that γ-mangostin exhibited prominent protection against H2O2- or xanthine/xanthine oxidase-induced oxidative neuronal death and inhibited reactive oxygen species (ROS) generation triggered by these oxidative insults. In contrast, α-mangostin had no effects on the oxidative neuronal damage or associated ROS production. We also found that γ-mangostin, not α-mangostin, significantly inhibited H2O2-induced DNA fragmentation and activation of caspases 3 and 9, demonstrating its antiapoptotic action. In addition, only γ-mangostin was found to effectively inhibit lipid peroxidation and DPPH radical formation, while both mangostins inhibited ß-secretase activity. Furthermore, we observed that the oral administration of γ-mangostin at dosages of 10 and 30 mg/kg markedly improved scopolamine-induced memory impairment in mice. Collectively, these results provide both in vitro and in vivo evidences for the neuroprotective and memory enhancing effects of γ-mangostin. Multiple mechanisms underlying this neuroprotective action were suggested in this study. Based on our findings, γ-mangostin could serve as a potentially preferable candidate over α-mangostin in combatting oxidative stress-associated neurodegenerative diseases including Alzheimer's disease.


Assuntos
Transtornos da Memória/tratamento farmacológico , Neurotoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Xantonas/uso terapêutico , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/patologia , Peróxido de Hidrogênio/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos ICR , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Picratos/química , Ratos Sprague-Dawley , Escopolamina , Xantonas/química , Xantonas/farmacologia
14.
Molecules ; 24(7)2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30986967

RESUMO

We aimed to purify polyphenols from distiller's grain extract using macroporous resins and to identify its polyphenolic components. The influence of operational parameters on purification efficiency was investigated. The polyphenolic composition was analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and then quantified by UPLC-MS using authenticated standards. The results showed that the optimal purifying conditions were D101 resin with a dosage of 3 g, four hours adsorption, three hours desorption time, and 60% ethanol as the eluent, producing the highest purification rate of 51%. The purified distiller's grain extract exhibited stronger antioxidant activity than the unpurified extracts, which was assessed using DPPH and ABTS methods (IC50 DPPH = 34.03 and 16.21 µg/mL, respectively; IC50 ABTS = 20.31 and 5.73 µg/mL, respectively). UPLC-MS results indicated that (-)-epicatechin is the major compound found in distiller's grain extract which was quantified as 562.7 µg/g extract, followed by ferulic acid (518.2 µg/g), p-hydroxybenzoic acid (417.7 µg/g), caffeic acid (217.1 µg/g), syringic acid (158.0 µg/g) and quercetin (147.8 µg/g). Two compounds, vanillic acid (66.5 µg/g) and gallic acid (41.4 µg/g), were found in lower concentrations. The findings of this study suggest that purification of polyphenolic compounds from distiller's grain by macroporous resins is feasible, providing a new and effective method for the secondary use of distiller's grain resources.


Assuntos
Polifenóis/isolamento & purificação , Resinas Vegetais/química , Benzotiazóis/química , Benzotiazóis/isolamento & purificação , Compostos de Bifenilo/química , Compostos de Bifenilo/isolamento & purificação , Ácidos Cafeicos/química , Ácidos Cafeicos/isolamento & purificação , Cromatografia Líquida , Ácidos Cumáricos/química , Ácidos Cumáricos/isolamento & purificação , Ácido Gálico/análogos & derivados , Ácido Gálico/química , Ácido Gálico/isolamento & purificação , Hidroxibenzoatos/química , Hidroxibenzoatos/isolamento & purificação , Picratos/química , Picratos/isolamento & purificação , Polifenóis/química , Quercetina/química , Quercetina/isolamento & purificação , Ácidos Sulfônicos/química , Ácidos Sulfônicos/isolamento & purificação , Espectrometria de Massas em Tandem , Ácido Vanílico/química , Ácido Vanílico/isolamento & purificação
15.
Int J Biol Macromol ; 132: 524-533, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30936007

RESUMO

The roots of Stipa species have been used for treatment and prevention of a various number of diseases. To the best of my knowledge, little information is regarding the antioxidant and hepatoprotective activities of polysaccharides from Stipa parviflora (SPP). Hence the polysaccharides from this plant sample have been investigated here. In addition, Box-Behnken design and response surface methodology were used to optimize the hot extraction conditions. The optimal conditions were determined as: extraction time 120 min, extraction temperature 70 °C and ratio of water to raw material 30. Crude SPP was composed of mannose, ribose, glucose, galactose, pyranose and arabinose. In addition, the SPP showed a strong antioxidant capacity in vitro. In vivo experiments showed that CCl4 treatment caused significant oxidative damage in hepatic tissues, whereas these problems were inhibited by SPP treatment. Hepatoprotective potential of SPP was evaluated by estimating the levels of serum markers like ALT and AST levels. SPP treated rat liver anti-oxidant parameters (SOD, CAT and GPx) were significantly antagonized for the pro-oxidant effect of CCl4. Histopathological studies proved that the SPP extract has significant hepatoprotective activity. In conclusion, the SPP fraction isolated from S. parviflora showed significant hepatoprotective potential which could be related to active compounds present in this fraction.


Assuntos
Antioxidantes/farmacologia , Tetracloreto de Carbono/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Citoproteção/efeitos dos fármacos , Fígado/efeitos dos fármacos , Poaceae/química , Polissacarídeos/farmacologia , Animais , Antioxidantes/química , Benzotiazóis/química , Compostos de Bifenilo/química , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Picratos/química , Polissacarídeos/química , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Ácidos Sulfônicos/química
16.
Int J Biol Macromol ; 132: 880-887, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30940585

RESUMO

The structural and optical properties of metal oxide nanoparticles exhibit remarkable changes when coated with organic polymers. In this work, we report the preparation of chitosan (CS) coated iron oxide nanocomposite using rutin by a facile greener route. The formation of iron oxide nanoparticles (FeO NPs) and CS coated iron oxide nanocomposite (CS-FeO) were preliminarily confirmed by color change and UV-Visible spectroscopy. FE-SEM images of FeO NPs revealed rod shaped agglomerated particles whereas CS-FeO nanocomposite showed rod shaped agglomerated small grains. TEM analysis revealed that the size of the nanoparticles varies from 20 to 90 nm. The observed bands at 500-800 cm-1 in the FTIR spectrum indicated the presence of metal­oxygen (FeO) bond, whereas band at 1646 cm-1 indicated the presence of amino groups (-NH2) which confirms the CS in the prepared CS-FeO nanocomposite. The prepared nanoparticles showed potential antibacterial activity against both Gram-positive and Gram-negative bacterial pathogens. The antioxidant activity of FeO NPs and CS-FeO nanocomposite was evaluated by DPPH and H2O2 assays. The percentage of antioxidant activity was increased with increasing concentration of FeO NPs and CS-FeO nanocomposite. CS-FeO nanocomposite exhibiting potentially better biomedical property than the uncoated FeO NPs indicates that CS-FeO nanocomposite is a promising bio-nanomaterial for many biological applications.


Assuntos
Quitosana/química , Compostos Férricos/química , Nanocompostos/química , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Compostos de Bifenilo/química , Técnicas de Química Sintética , Escherichia coli/efeitos dos fármacos , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Peróxido de Hidrogênio/química , Nanopartículas/química , Nanotecnologia , Picratos/química , Staphylococcus aureus/efeitos dos fármacos
17.
Curr Pharm Biotechnol ; 20(5): 433-444, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30963968

RESUMO

BACKGROUND: Currently, the treatment of infectious diseases has not always been successful due to the emergence of microbial resistance worldwide. OBJECTIVES: This study aimed to evaluate the antioxidant activity, content of total phenolic compounds and flavonoids, antifungal potential and antibacterial action of six medicinal plants found in the Cerrado, leaf extracts of Boldo (Peumus boldus), Goiaba (Psidium guajava), Assa-Peixe (Vernonia polysphaera), Abacate (Persea americana), Eucalipto (Eucalyptus citriodora) and raw sap of Bálsamo (Jatropha multifida). METHODS: The antioxidant activity was also determined through the DPPH, ABTS and phosphomolybdenum assays. In addition, the total phenolic content and flavonoid dosage were analyzed using the Folin- Ciocalteu method and the aluminum chloride test, respectively. RESULTS: All extracts, except from Assa-Peixe, showed promising values against Staphylococcus aureus, with halos varying from 13-20 mm. Analysis of the minimum inhibitory concentration (MIC) values of the six medicinal plants revealed inhibitory activity of S. aureus, with concentrations varying from 3.12-12.5 mg/mL, which is a significant result considering that S. aureus is one of the main causes of hospital infections. CONCLUSION: In the analysis of the phytochemical profile, Goiaba contained the best yield of phenolic compounds and total flavonoids, as well as higher antioxidant activity by DPPH and phosphomolybdenum, demonstrating that this species contains antioxidant components that can sequester free radicals under in vitro conditions. Therefore, the crude extracts investigated are promising and their antibacterial and antioxidant actions should be thoroughly studied.


Assuntos
Antibacterianos/isolamento & purificação , Antioxidantes/isolamento & purificação , Flavonoides/isolamento & purificação , Fenóis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/química , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Compostos de Bifenilo/química , Brasil , Etnofarmacologia , Flavonoides/farmacologia , Testes de Sensibilidade Microbiana , Fenóis/farmacologia , Picratos/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Staphylococcus aureus/efeitos dos fármacos
18.
Anal Bioanal Chem ; 411(14): 3135-3150, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30989267

RESUMO

Drimia species have been used since ancient times for their medicinal properties. Their bulbs are considered as the main source of secondary metabolites with biological activity but the chemical composition of the other plant parts has not yet been considered. The aim of this study is to contribute to the existing knowledge with new data on the total phenolic content, the antioxidant activity and the chemical profile of different parts of Drimia numidica. The total phenolic content was estimated by the Folin-Ciocalteu assay and the antioxidant activity with DPPH· and ABTS·+ reagents. The separation and the identification of the compounds were performed with liquid chromatography combined with time-of-flight high-resolution mass spectrometry (LC/Q-TOF/HRMS). The extract of leaves presented the highest phenolic content while the highest antioxidant activity was presented by the extract of flowers. Results of the chemical analysis verify the presence of bufadienolides and phenolic compounds. Graphical abstract.


Assuntos
Antioxidantes/análise , Antioxidantes/farmacologia , Drimia/química , Fenóis/análise , Fenóis/farmacologia , Estruturas Vegetais/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Benzotiazóis/química , Compostos de Bifenilo/química , Cromatografia Líquida/métodos , Indicadores e Reagentes/química , Limite de Detecção , Picratos/química , Reprodutibilidade dos Testes , Ácidos Sulfônicos/química
19.
Eur J Med Chem ; 172: 109-130, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30959322

RESUMO

Fluoroquinolones substituted with N-1 biphenyl and napthyl groups were discovered to act as catalytically inhibitors of human topoisomerases I and II, and to possess anti-proliferative activity in vivo. Structural requirements for these novel quinolones to inhibit catalytic activity of human topoisomerase I have not been explored. In this work novel derivatives of the N-1 biphenyl fluoroquinolone were designed, synthesized and evaluated to understand structural requirements of the C-3 carboxylic acid, C-6 fluorine, C-7 aminomethylpyrrolidine, C-8 methoxy, and the N-1 biphenyl functional groups for hTopoI inhibition. Characterization of each analog for inhibition of hTopoI catalytic inhibition reveals critical insight into structural requirements of these novel quinolones for activity. Additionally, results of DNA binding and modeling studies suggest that N-1 biphenyl fluoroquinolones intercalate between the DNA base pairs with the N-1 biphenyl functional group, rather than the quinolone core, and that this mode of DNA intercalation contributes to inhibition of hTopoI by these novel structures. The results presented here support further development and evaluation of N-1 biphenyl fluoroquinolone analogs as a novel class of anti-cancer agents that act through catalytic inhibition of hTopoI.


Assuntos
Compostos de Bifenilo/farmacologia , DNA Topoisomerases Tipo I/metabolismo , Fluoroquinolonas/farmacologia , Inibidores da Topoisomerase I/farmacologia , Compostos de Bifenilo/síntese química , Compostos de Bifenilo/química , Relação Dose-Resposta a Droga , Fluoroquinolonas/síntese química , Fluoroquinolonas/química , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Inibidores da Topoisomerase I/síntese química , Inibidores da Topoisomerase I/química
20.
Molecules ; 24(6)2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30893865

RESUMO

The decoction of the local plant Baccharis grisebachii is used as a digestive, gastroprotective, external cicatrizing agent and antiseptic in Argentine. A lyophilized decoction (BLD) from the aerial parts of this plant was evaluated regarding its anti-ulcer, antioxidant and cytotoxic activities and the bioactivities were supported by UHPLC-MS metabolome fingerprinting which revealed the presence of several small bioactive compounds. The antioxidant properties were evaluated by DPPH, TEAC, FRAP and lipoperoxidation inhibition in erythrocytes methods, and the antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The BLD showed a moderate free radical scavenging activity in the DPPH (EC50 = 106 µg/mL) and lipid peroxidation in erythrocytes assays (67%, at 250 µg/mL). However, the BLD had the highest gastroprotective effect at a dose of 750 mg/kg with a ninety-three percent inhibition of damage through a mechanism that involve NO and prostaglandins using the ethanol-induced gastric damage in a standard rat model. On the other hand, BLD does not induce cytotoxic changes on human tumor and no-tumor cell lines at the concentrations assayed. Regarding the metabolomic analysis, thirty-one compounds were detected and 30 identified based on UHPLC-OT-MS including twelve flavonoids, eleven cinnamic acid derivatives, one coumarin, one stilbene and two other different phenolic compounds. The results support that the medicinal decoction of Baccharis grisebachii is a valuable natural product with gastroprotective effects and with potential to improve human health that opens a pathway for the development of important phytomedicine products.


Assuntos
Antioxidantes/química , Baccharis/química , Compostos de Bifenilo/química , Cromatografia Líquida de Alta Pressão , Cinamatos/química , Flavonoides/química , Células HCT116 , Humanos , Peroxidação de Lipídeos , Espectrometria de Massas , Picratos/química
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