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1.
Phytochemistry ; 170: 112218, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31812108

RESUMO

The vast majority of previous studies dealing with antioxidant potency of (poly)phenols does not investigate the fate of phenoxyl radical obtained after single free radical scavenging. We investigated possible pathways of inactivation of ferulic acid phenoxyl radical (FAPR) using DFT method. Direct coupling with a set of 10 physiologically important free radicals, H-atom donation and dimerization were analysed by estimation of Gibbs free energy changes related to these processes. The former two processes are thermodynamically feasible to inactivate more dangerous free radicals such as hydroxyl, alkoxyl and carbon-centered radicals. Among dimerization reactions, the least energy demanding is formation of C-5-C-5 dimer of ferulic acid (FA), which has higher antiradical potency than FA itself. Obtained results reveal that FAPR, a priori considered as stable and unreactive, may contribute to the overall antioxidant activity of FA. This is a beneficial behavior, which makes FA a particularly valuable protector against oxidative stress. Hence, the contribution of phenoxyl radicals to the antioxidant activity of (poly)phenolic compounds should be taken into account, what has been scarcely considered until now.


Assuntos
Antioxidantes/farmacologia , Ácidos Cumáricos/farmacologia , Fenóis/farmacologia , Compostos Fitoquímicos/farmacologia , Antioxidantes/química , Ácidos Cumáricos/química , Teoria da Densidade Funcional , Radicais Livres/química , Radicais Livres/farmacologia , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Fenóis/química , Compostos Fitoquímicos/química
2.
Food Chem ; 309: 125586, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31670124

RESUMO

Oil-in-water (O/W) emulsions are important delivery systems of omega-3 fatty acids (n-3 FA). We investigated the effect of sinapic acid esters concentration and chain length, the electrical charge of the emulsifier and emulsion pH on the oxidative stability of n-3 FA rich O/W emulsions. Echium oil was applied as n-3 FA source. A 24 factorial design was used to simultaneously evaluate these factors. Peroxide value, malondialdehyde, 2,4-heptadienal and 2,4-decadienal were measured in the emulsions. pH and the electrical charge of the emulsifier modulated the antioxidant effectiveness of sinapic acid esters, while concentration was not relevant. The combination of positively charged emulsifier with neutral pH provided the best oxidative stability for echium oil emulsions. Our results also suggested that the increase of length chain of sinapic acid, from C4 to C12, reduced the secondary products of oxidation, when echium oil emulsions were prepared using negatively charged emulsifier under acidic conditions.


Assuntos
Ácidos Cumáricos/química , Ácidos Graxos Ômega-3/química , Antioxidantes/química , Antioxidantes/farmacologia , Ácidos Cumáricos/farmacologia , Echium/química , Emulsões , Ésteres , Oxirredução , Óleos Vegetais/química
3.
Biol Pharm Bull ; 42(10): 1694-1706, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582657

RESUMO

Alzheimer's disease (AD) is the most common form of dementia and its prevention and treatment is a worldwide issue. Many natural components considered to be effective against AD have been identified. However, almost all clinical trials of these components for AD reported inconclusive results. We thought that multiple factors such as amyloid ß (Aß) and tau progressed the pathology of AD and that a therapeutic effect would be obtained by using multiple active ingredients with different effects. Thus, in this study, we treated ferulic acid (FA), phosphatidylserine (PS) and curcumin (Cur) in combination or alone to APPswe/PS1dE9 transgenic mice and evaluated cognitive function by Y-maze test. Consequently, only the three-ingredient group exhibited a significant improvement in cognitive function compared to the control group. In addition, we determined the amounts of Aß, brain-derived neurotrophic factor (BDNF), interleukin (IL)-1ß, acetylcholine and phosphorylated tau in the mouse brains after the treatment. In the two-ingredient (FA and PS) group, a significant decrease in IL-1ß and an increasing trend in acetylcholine were observed. In the Cur group, significant decreases in Aß and phosphorylated tau and an increasing trend in BDNF were observed. In the three-ingredient group, all of them were observed. These results indicate that the intake of multiple active ingredients with different mechanisms of action for the prevention and treatment of AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Ácidos Cumáricos/uso terapêutico , Curcumina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Fosfatidilserinas/uso terapêutico , Acetilcolina/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Curcumina/farmacologia , Quimioterapia Combinada , Interleucina-1beta/metabolismo , Camundongos Transgênicos , Fármacos Neuroprotetores/farmacologia , Fosfatidilserinas/farmacologia , Presenilina-1/genética , Proteínas tau/metabolismo
4.
Free Radic Res ; 53(9-10): 944-967, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31576765

RESUMO

The major drawback of anticancer therapy is the development of resistance against drugs and radiation at the later phase of treatment which may lead to recurrences of the disease. Therefore, strategy was taken to enhance radiation sensitivity of lung (A549) and liver (HepG2) carcinoma cells by treatment with ferulic acid (FA) prior to irradiation. FA pre-treatment initially decreased reactive oxygen species (ROS) level in carcinoma cells which induced reductive stress and cytostasis. To overcome this stress, cellular mechanism increased the Keap1 level to down-regulate nuclear localisation of Nrf2 and its dependent antioxidant system. The antioxidant system reached the lowest level after 3 and 6 h of FA treatment in A549 and HepG2 cells respectively. As endogenous ROS were still being generated at same rate, ROS level was clearly higher than control which changed the reductive stress to oxidative stress. Exposure to γ-radiation in this condition further increased ROS level and caused radio-sensitisation of carcinoma cells. Combination of irradiation (IR) and FA activated mitochondrial apoptotic pathway and concomitantly inhibited the cell cycle progression and survival pathway over the IR group. Moreover, the combination treatment showed significant tumour regression, caspase 3 activation and nuclear fragmentation in tumour tissue compared to radiation alone. In contrast, FA pre-treatment protected peripheral blood mononuclear cells (PBMC) and normal lung fibroblast WI38 cells from radiation damage. Together, combination treatment offers effective strategy of killing cancer cells and demonstrates its potential for increasing the efficacy of radio-therapy.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Ácidos Cumáricos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular , Ácidos Cumáricos/farmacologia , Homeostase/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Oxirredução
5.
J Zhejiang Univ Sci B ; 20(11): 868-876, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31595723

RESUMO

Acrolein, known as one of the most common reactive carbonyl species, is a toxic small molecule affecting human health in daily life. This study is focused on the scavenging abilities and mechanism of ferulic acid and some other phenolic acids against acrolein. Among the 13 phenolic compounds investigated, ferulic acid was found to have the highest efficiency in scavenging acrolein under physiological conditions. Ferulic acid remained at (3.04±1.89)% and acrolein remained at (29.51±4.44)% after being incubated with each other for 24 h. The molecular mechanism of the detoxifying process was also studied. Detoxifying products, namely 2-methoxy-4-vinylphenol (product 21) and 5-(4-hydroxy-3-methoxyphenyl)pent-4-enal (product 22), were identified though nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS), after the scavenging process. Ferulic acid showed significant activity in scavenging acrolein under physiological conditions. This study indicates a new method for inhibiting damage from acrolein.


Assuntos
Acroleína/toxicidade , Ácidos Cumáricos/farmacologia , Acroleína/química , Ácidos Cumáricos/química , Glutationa/fisiologia , Hidroxibenzoatos/farmacologia , Espectroscopia de Ressonância Magnética , Relação Estrutura-Atividade
6.
Mol Cell Biochem ; 462(1-2): 25-31, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31440879

RESUMO

Resveratrol, a phytoalexin present in grapes and other edible foods, has been reported to have beneficial effects against various diseases including cancer. We previously reported that resveratrol and its derivative, caffeic acid-adducted resveratrol, selectively inhibit the three-dimensional (3D) proliferation of a human colorectal cancer cell line, HCT116 with activating KRAS mutation. Herein, we demonstrated that a novel compound, ferulic acid-bound resveratrol, also represses the 3D proliferation of HCT116 cells. We observed that resveratrol conjugated to two ferulic acids represses the 3D proliferation of HCT116 cells more strongly than resveratrol and resveratrol conjugated to one ferulic acid. Resveratrol conjugated to two ferulic acids also inhibited the 3D proliferation of MCF7 human breast cancer cells. We further uncovered that the resveratrol derivative increases the mRNA level of the tumor suppressor p15, a CDK inhibitor that functions as a brake of cell proliferation in HCT116 cells. These results imply that the resveratrol derivative represses 3D proliferation via increasing p15 expression in HCT116 cells.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ácidos Cumáricos/farmacologia , Inibidor de Quinase Dependente de Ciclina p15/genética , Genes Supressores de Tumor , Resveratrol/farmacologia , Proliferação de Células/efeitos dos fármacos , Ácidos Cumáricos/química , Inibidor de Quinase Dependente de Ciclina p15/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos , Concentração Inibidora 50 , Células MCF-7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Resveratrol/química
7.
Int J Nanomedicine ; 14: 4589-4599, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31296988

RESUMO

Purpose: Ferulic acid (FA) is a poorly water-soluble natural antioxidant with anticancer activity. This poor solubility limits the application of FA in the food and pharmaceutical industry. Cyclodextrin nanosponges (CD-NSs) are a novel group of cross-linked CD derivatives which can be used to enhance the solubility of low-soluble bioactive compounds. Methods: In this study, FA was encapsulated into the NSs in the proportion of 1:4 (FA:NS). Diphenyl carbonate was used as a cross-linker in different proportions with ß-CD. Characterization of obtained NSs was performed using scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analysis. Results: Our results revealed that the solubility of encapsulated FA was increased up to fifteenfold compared with pure FA in the proportion of 1:4 (CD:cross-linker). The results of FTIR, XRD, and DSC confirmed the interaction of FA with NSs. The cytotoxicity of encapsulated FA against MCF7 and 4T1 breast cancer cell lines was investigated using different concentrations of FA in 24, 48, and 72 hrs. The cytotoxicity assay indicated that FA treatment reduced viability and enhanced apoptosis of cancer cells. IC50 value of encapsulated FA (250 ppm) was decreased by threefold when compared with pure FA (750 ppm). Conclusion: In general, CD-NS was found to be a suitable delivery system for poorly soluble bioactives such as FA.


Assuntos
Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Ciclodextrinas/química , Nanoestruturas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Varredura Diferencial de Calorimetria , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Feminino , Humanos , Microscopia Eletrônica de Varredura , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X
8.
J Oleo Sci ; 68(8): 765-768, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31292340

RESUMO

γ-Oryzanol is a naturally occurring component of rice bran and consists of various steryl ferulates. The antioxidant activities of γ-oryzanol have mostly been demonstrated in cell-free systems. Therefore, we determined whether steryl ferulate of γ-oryzanol suppress spontaneous intracellular reactive oxygen species (ROS) in cell-based systems. We found that cycloartenyl ferulate and ß-sitosteryl ferulate suppressed spontaneous intracellular ROS in a similar way to N-acetylcysteine and α-tocopherol.


Assuntos
Antioxidantes/farmacologia , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Ácidos Cumáricos/farmacologia , Fenilpropionatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sitosteroides/farmacologia , Células HT29 , Humanos
9.
Int J Mol Sci ; 20(13)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269760

RESUMO

Chenopodium quinoa Wild is a "pseudocereal" grain which attracts a lot of attention in the scientific community as it has a positive effect on health. Here, we investigate the presence of biologically active O-prenylated phenylpropanoids in the ethanol extract of commercially available quinoa seeds. We claim that 4'-Geranyloxyferulic acid (GOFA) was the only phytochemical product found that belongs to quinoa's group secondary metabolites. We studied the changes in the oxidative and inflammatory status of the cellular environment in HCT 116 cell line processed with quinoa extract and its component GOFA; the implementation was done through the analysis of the antioxidant enzymes (SOD and CAT), the pro-inflammatory components (iNOS, IL-6 and TNF-α), and the products of intermediary metabolism (ONOO-, O2-). Moreover, the l-arginine uptake was proposed as a target of the tested compounds. We demonstrated that the GOFA, through a decrease of the CAT-2B expression, leads to a reduction of the l-arginine uptake, downregulating the harmful iNOS and restoring the altered redox state. These results propose a new molecular target involved in the reduction of the critical inflammatory process responsible for the cancer progression.


Assuntos
Anticarcinógenos/farmacologia , Arginina/metabolismo , Transportador 2 de Aminoácidos Catiônicos/metabolismo , Ácidos Cumáricos/farmacologia , Óxido Nítrico/metabolismo , Anticarcinógenos/química , Chenopodium quinoa/química , Ácidos Cumáricos/química , Células HCT116 , Humanos , Inflamação/metabolismo , Inflamação/prevenção & controle , Neoplasias/metabolismo , Neoplasias/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Sementes/química
10.
Eur J Med Chem ; 180: 111-120, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31301562

RESUMO

N-methyl-d-aspartate receptors (NMDAR) are critically involved in the pathogenesis of Alzheimer's disease (AD). Acting as an open-channel blocker, the anti-AD drug memantine preferentially targets NMDAR overactivation, which has been proposed to trigger neurotoxic events mediated by amyloid ß peptide (Aß) and oxidative stress. In this study, we applied a multifunctional approach by conjugating memantine to ferulic acid, which is known to protect the brain from Aß neurotoxicity and neuronal death caused by ROS. The most interesting compound (7) behaved, like memantine, as a voltage-dependent antagonist of NMDAR (IC50 = 6.9 µM). In addition, at 10 µM concentration, 7 exerted antioxidant properties both directly and indirectly through the activation of the Nrf-2 pathway in SH-SY5Y cells. At the same concentration, differently from the parent compounds memantine and ferulic acid alone, it was able to modulate Aß production, as revealed by the observed increase of the non-amyloidogenic sAPPα in H4-SW cells. These findings suggest that compound 7 may represent a promising tool for investigating NMDAR-mediated neurotoxic events involving Aß burden and oxidative damage.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/antagonistas & inibidores , Ácidos Cumáricos/farmacologia , Memantina/farmacologia , Fármacos Neuroprotetores/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ácidos Cumáricos/síntese química , Ácidos Cumáricos/química , Relação Dose-Resposta a Droga , Humanos , Memantina/síntese química , Memantina/química , Estrutura Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Estresse Oxidativo/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
11.
Int J Biol Macromol ; 138: 244-251, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31279877

RESUMO

The objective of this study was to develop zein-casein-lysine nanoparticles to modulate the intestinal permeability of ferulic acid (FA), a bioactive compound with proven antioxidant properties. The nanoparticles were obtained by a liquid-liquid dispersion method and were characterized in terms of mean size, polydispersity index, zeta potential, association efficiency (AE), in vitro drug release, x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). The in vitro intestinal permeability of nanoparticles was evaluated through Caco-2 and Caco-2/HT29-MTX monoculture and co-culture models, respectively. Nanoparticles presented a mean size of 199 nm and zeta potential of -26 mV. The AE of FA was 23% evaluated by high-performance liquid chromatography (HPLC). XRD showed amorphization of FA after association and FT-IR showed no changes in chemical structures of the compounds after nanoencapsulation. The cytotoxicity assays demonstrated that multicomposite nanoparticles presented a safe profile against Caco-2 and HT29-MTX cells. In the in vitro permeability assay, free FA exhibited higher permeability compared to FA-loaded nanoparticles, possibly due to prolonged FA release from nanoparticles. These new developed zein-casein-lysine nanoparticles may be used for FA sustained delivery by the oral route.


Assuntos
Caseínas/química , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Mucosa Intestinal/metabolismo , Lisina/química , Nanopartículas/química , Zeína/química , Administração Oral , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Ácidos Cumáricos/administração & dosagem , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Mucosa Intestinal/efeitos dos fármacos
12.
Eur J Pharmacol ; 858: 172482, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31233749

RESUMO

In the present study, we report that neolignan1 (Diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate) relaxes the superior mesenteric artery in a concentration dependent manner (pD2 value 5.392 ±â€¯0.04; n = 8 for endothelium intact and 5.204 ±â€¯0.03; n = 8 for endothelium denuded mesenteric rings, respectively). The relaxation response of neolignan1 was found to be endothelium independent and sensitive to 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-on (ODQ; 1 µM) and tetraethyl ammonium (TEA; 1 mM). In-silico studies showed good LibDock score (92.66) of neolignan1 with BKCa channel and are in well corroboration with ex-vivo study. Further, neolignan1 significantly decreased the systolic blood pressure, diastolic blood pressure and mean arterial pressure in the Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME; 50 mg/kg) treated Wistar rats at the dose of 30 and 100 mg/kg given once orally for 15 days. In addition, neolignan1 is well tolerated up to 100 mg/kg when given as a repeated dose, once orally for 28 days in Swiss albino mice. Neolignan1 was well absorbed from oral route, reached peak at 4 h and eliminated below detection level by 12 h after administration. Our present study concludes that neolignan1 produced relaxation in superior mesenteric artery by opening of BKCa channel and produced significant antihypertensive activity in L-NAME treated Wistar rats and was well tolerated by the experimental animal.


Assuntos
Anti-Hipertensivos/farmacologia , Ácidos Cumáricos/farmacologia , Lignanas/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Animais , Anti-Hipertensivos/metabolismo , Anti-Hipertensivos/farmacocinética , Ácidos Cumáricos/metabolismo , Ácidos Cumáricos/farmacocinética , Feminino , Humanos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/química , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Lignanas/metabolismo , Lignanas/farmacocinética , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiologia , Camundongos , Simulação de Acoplamento Molecular , Conformação Proteica , Ratos , Ratos Wistar , Vasodilatação/efeitos dos fármacos
13.
Molecules ; 24(11)2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31181779

RESUMO

Lung cancer is one of the most common malignancies and is an increasing cause of cancer-related deaths. In our previous study, a series of ferulic acid (FA) derivatives were designed and synthesized; they exhibited positive anti-cancer activities, especially for a compound labelled FXS-3. In this study, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed, wherein it revealed the inhibitory effect of FXS-3 on the proliferation and metastasis of human lung cancer A549 cells. The further flow cytometry assay showed that FXS-3 induced apoptosis of A549 cells induced cell cycle arrest at the G0/G1 phase. The trans-well migration and Matrigel invasion assays revealed that FXS-3 inhibited the migration and invasion of A549 cells. By the western blotting analysis, FXS-3 increased the expression of B-cell lymphoma-2 (Bcl-2) associated X protein (Bax)/Bcl-2 ratio, inhibited matrix metalloproteinase (MMP)-2 and MMP-9, and regulated the extracellular signal-regulated kinase (ERK)/p38, c-Jun N-terminal kinase (JNK), protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), as well as mitogen-activated protein kinase (MEK)/ERK signaling pathways. The subsequent A549 xenograft-bearing mouse model and tail vein injection of A549 cells induced pulmonary tumor metastasis model showed that FXS-3 significantly restrained the tumor growth and metastasis. In conclusion, FXS-3 might inhibit proliferation and metastasis of human lung cancer A549 cells by positively regulating JNK signaling pathway and negativly regulating ERK/p38, AKT/mTOR, and MEK/ERK signaling pathways, which provides important scientific basis for the development of anti-cancer drugs about FA derivatives.


Assuntos
Ácidos Cumáricos/farmacologia , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Células A549 , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácidos Cumáricos/química , Humanos , Masculino , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Food Chem Toxicol ; 130: 130-141, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31103739

RESUMO

Laba garlic is a kind of processed garlic products, it is the traditional Chinese food with a long history. In this study, the antitumor, antioxidant and cytotoxic properties of the blue pigment (BP) from Laba garlic were investigated. N-trans-feruloyltyramine (FLA) was isolated and identified from BP. The protective effects of FLA against H2O2-induced oxidative damages in L02 cells were also assessed. The apoptotic effects of FLA were detected by using flow cytometry analysis. Results showed that the tumor growth was significantly suppressed by BP (P<0.05). BP and FLA exhibited remarkable antioxidant activities. L02 cells pretreatment with FLA could significantly fight against the oxidative damage induced by H2O2, inhibit the morphological changes of mitochondria and maintain the integrity of mitochondria. FLA showed proliferation inhibition on HepG2 cells with IC50 value of 194 ±â€¯0.894 µM. After treatment of FLA (320 µM), the results of MTT assay on HepG2 and L02 cells indicated that FLA had selective cytotoxic effects. It suggested a new way of prevention and treatment of tumors and FLA might be a promising candidate in cancer therapy and functional foods.


Assuntos
Antioxidantes/farmacologia , Ácidos Cumáricos/farmacologia , Alho/química , Peróxido de Hidrogênio/toxicidade , Tiramina/análogos & derivados , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Manipulação de Alimentos , Humanos , Masculino , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tiramina/farmacologia
15.
Environ Sci Pollut Res Int ; 26(20): 20631-20653, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104231

RESUMO

The aim of this study relates to the modulatory role of ferulic acid (FA) against cadmium (Cd)-induced oxidative stress in the liver and kidney of male Wistar albino rats. Cd is an extremely toxic industrial and environmental pollutant and is well known for its varied toxic clinical manifestations. FA is a derivative of curcumin and a ubiquitous phenolic compound having a wide range of therapeutic activities. In the current study, Cd (10 mg/kg) was administered subcutaneously for 15 and 30 days to induce hepato-renal toxicity. Cd concentration was found to be significantly high in Cd-intoxicated rats (liver > kidney) while the supplementation of FA (50 mg/kg) significantly reduces the Cd concentration in liver and kidney tissues. Reduced body and organ weights and food and water consumption and increased rectal temperature were noticed in Cd-treated rats while these parameters were significantly ameliorated in FA-supplemented rats. Liver and kidney damage induced by Cd was significantly revealed by the reduction in serum total protein contents (TPC) and increased activities of serum nitric oxide (NO) levels and hepato-nephrotoxicity marker enzymes, namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactic dehydrogenase (LDH), AST:ALT ratio, uric acid, urea, urea nitrogen, and creatinine, along with the increased levels of hepatic and renal oxidative stress markers, namely lipid peroxidation (MDA levels), lipid hydroperoxides (LOOH), protein carbonyl content (PCC), total oxidant status (TOS), and oxidative stress index (OSI) in liver and kidney tissues. In addition, the toxicity of Cd was also evidenced by a significant decrease in the levels of total thiols (TTH), total antioxidant concentration (TAC), enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), and non-enzymatic antioxidants (reduced glutathione (GSH) and total free sulfhydryl groups (TSH)). Administration of FA significantly restored the serum total protein levels and activities of serum NO levels and hepatic and renal marker enzymes to normal levels in comparison with Cd-intoxicated rats. Furthermore, FA significantly reduced the oxidative stress markers and recuperated the levels of antioxidant defense in the liver and kidney as evidenced by native PAGE and spectrophotometric assays, correlation and regression analysis and multivariate analysis of variance (MANOVA), and inferring the antioxidant role of FA. Histopathological damage due to Cd intoxication in the liver and kidney is demonstrated as vasodilatation and congestion in central veins and sinusoids as well as around the glomerulus, infiltration of mixed inflammatory cells and peripheral hemorrhage, hemorrhagic and enlarged sinusoids, disorganization of the hepatic parenchyma, focal necrosis, swelling of hepatocytes, calcified tissue inside blood vessels, hepatocyte degeneration and vacuolization of liver cells, hyaline casts, degenerated glomerulus with wide space and detached basement membrane, distal tubule with wide lumen, deformed proximal tubules with detached brush border, and degeneration and hyalinization of glomerular tuft. But, FA significantly reduced the toxicity of Cd and protected the normal histological architecture of the liver and kidney tissues. Cd-intoxicated rats were associated with a significant upregulation of TNF-α, COX-2, and HSP70 proteins, whereas treatment with FA caused downregulation of the above inflammatory markers indicating the anti-inflammatory role of FA. Principal component analysis (PCA) and Euclidean similarity measure studies clearly indicate that the liver is more prone to Cd toxicity than the kidney and FA supplementation significantly prevents oxidative stress, augmenting antioxidative status, and regaining histological parameters of the liver and kidney to normal, indicating hepato-nephroprotective, antiradical, antioxidant, and anti-inflammatory effects of this phenolic compound.


Assuntos
Antioxidantes/farmacologia , Cádmio/toxicidade , Ácidos Cumáricos/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Biomarcadores/metabolismo , Suplementos Nutricionais , Inflamação/metabolismo , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos Wistar
16.
Bratisl Lek Listy ; 120(5): 372-379, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31113201

RESUMO

AIM: Traumatic brain injury is an important social health problem due to the fact that young adults are more likely to be affected, and advanced functional limitations are observed in survivors. In this study, we aimed to investigate the protective effect of ferulic acid in an experimental trauma model. MATERIAL AND METHODS: This study was performed in March 2016 at Dokuz Eylül University Experimental Animal Laboratory. Subjects were randomly divided into 4 groups Control, Ethyl Alcohol, Trauma, Trauma/Ferulic Acid groups. For histological findings, Cresyl violet; for immunohistochemical analysis, TUNEL and Active Caspase-3 staining were used. For biochemical analysis, Superoxide dismutase, Malondialdehyde, and Glutathione values ​​were examined. RESULTS: The application of ferulic acid has been shown to primarily reduce neuronal apoptosis, the levels of free radicals, and to effect oxidant/antioxidant balance positively by increasing the levels of antioxidants, such as Superoxide dismutase and Glutathione that are developed due to brain damage. Our study group has shown that ferulic acid decreased nerve tissue pathologies after generated brain trauma compared to injury groups. CONCLUSION: Addition of ferulic acid to the traditional head trauma treatment has the strength, and ability to increase the rate, and percentage of healing (Tab. 2, Fig. 4, Ref. 28).


Assuntos
Anti-Inflamatórios não Esteroides , Lesões Encefálicas Traumáticas , Ácidos Cumáricos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes , Encéfalo , Lesões Encefálicas Traumáticas/tratamento farmacológico , Ácidos Cumáricos/farmacologia , Malondialdeído , Ratos , Superóxido Dismutase
17.
Nutrients ; 11(5)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075850

RESUMO

4-Hydroxy-3-methoxycinnamic acid (HMCA), a hydroxycinnamic acid derivative, is abundant in fruits and vegetables, including oranges, carrots, rice bran, and coffee beans. Several beneficial effects of HMCA have been reported, including improvement of metabolic abnormalities in animal models and human studies. However, its mitigating effects on high-fat diet (HFD)-induced obesity, and the mechanism underlying these effects, remain to be elucidated. In this study, we demonstrated that dietary HMCA was efficacious against HFD-induced weight gain and hepatic steatosis, and that it improved insulin sensitivity. These metabolic benefits of HMCA were ascribable to 3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) produced by gut microbiota. Moreover, conversion of HMCA into HMPA was attributable to a wide variety of microbes belonging to the phylum Bacteroidetes. We further showed that HMPA modulated gut microbes associated with host metabolic homeostasis by increasing the abundance of organisms belonging to the phylum Bacteroidetes and reducing the abundance of the phylum Firmicutes. Collectively, these results suggest that HMPA derived from HMCA is metabolically beneficial, and regulates hepatic lipid metabolism, insulin sensitivity, and the gut microbial community. Our results provide insights for the development of functional foods and preventive medicines, based on the microbiota of the intestinal environment, for the prevention of metabolic disorders.


Assuntos
Ácidos Cumáricos/farmacologia , Dieta , Microbioma Gastrointestinal/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Obesidade/metabolismo , Propionatos/farmacologia , Animais , Bacteroidetes/efeitos dos fármacos , Bacteroidetes/crescimento & desenvolvimento , Bacteroidetes/metabolismo , Citrus sinensis/química , Coffea/química , Ácidos Cumáricos/metabolismo , Daucus carota/química , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/etiologia , Fígado Gorduroso/prevenção & controle , Firmicutes/crescimento & desenvolvimento , Firmicutes/metabolismo , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Resistência à Insulina , Fígado/metabolismo , Fígado/patologia , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Doenças Metabólicas/prevenção & controle , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/complicações , Obesidade/etiologia , Oryza/química , Plantas Comestíveis/química , Propionatos/metabolismo , Ganho de Peso/efeitos dos fármacos
18.
Genesis ; 57(9): e23291, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31140714

RESUMO

We aimed to investigate the potential beneficial effect of ferulic acid (FA) on stemness of human tendon-derived stem cells (hTSCs) in vitro and to elucidate the underlying molecular mechanism. The self-renewal ability of hTSCs was evaluated by colony formation and cell proliferation was determined by CCK-8 kit. Adipogenesis, osteogenesis, and chondrogenesis were determined by Oil Red O, Alizarin Red, and Alcian Blue stainings, respectively. Relative mRNA levels of PPARγ, Col2A1, Acan, Runx2, HIF1α, and EGR1 were measured with real-time PCR. Protein levels of HIF1α and EGR1 were detected by western blot. Direct binding of HIF1α with EGR1 promoter was analyzed by ChIP assay. Hypoxia-induced expression of EGR1 was interrogated by luciferase reporter assay. We demonstrated that FA treatment improved both self-renewal ability and multi-differentiation potential of hTSCs. FA induced hypoxia which in turn upregulated EGR1 expression via direct association with its hypoxia response element consensus sequence. Furthermore, we showed that both HIF1α and EGR1 were required for the enhancing effects of FA on hTSC self-renewal and differentiation. We hereby characterize the beneficial effect of FA on the stemness of hTSCs and highlight the critical role of HIF1α-EGR1 axis in this process.


Assuntos
Indutores da Angiogênese/farmacologia , Diferenciação Celular/efeitos dos fármacos , Hipóxia Celular , Ácidos Cumáricos/farmacologia , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Células-Tronco/efeitos dos fármacos , Tendões/citologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Proteína 1 de Resposta de Crescimento Precoce/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células-Tronco/metabolismo , Tendões/efeitos dos fármacos , Tendões/metabolismo , Regulação para Cima/efeitos dos fármacos
19.
Eur J Pharmacol ; 856: 172417, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31132358

RESUMO

The molecular structure optimization aimed at definite target is expected to improve its anti-myocardial ischemia reperfusion (I/R) injury. Ferulic acid derivatives could probably attenuate myocardial I/R injury when optimized on account of definite target succinate dehydrogenase (SDH). Herein, an original compound hmy-paa (3-(4-hydroxy-3-methoxyphenyl)-N-(1H-pyrazol-3-yl)acrylamide), a combination of ferulic acid and active groups of enzyme inhibitor was synthesized, myocardial cell hypoxia reoxygenation (H/R) model were built, and SDH activity of myocardial cell was detected to investigate the effect of the derivative. Intriguingly, it could selectively inhibit SDH activity, and efficiently abate myocardial cell H/R injury. SDH is located in the mitochondrial inner membrane, and fluorescent hmy-paa could be observed to accumulate in cell and mitochondria through fluorescence inversion microscopy, which allows for more efficient SDH inhibition efficacy. By inhibiting SDH activity, hmy-paa could reduce oxidative damage by preventing excess production of intracellular reactive oxygen species as well as ensure energy production through the regulation of ATP level. The computational docking simulation exhibits a tightly bound mode between hmy-paa and SDH. Consequently, ferulic acid derivative hmy-paa is a new candidate for the treatment of myocardial H/R injury that exerts its therapeutic effect through a SDH dependent antioxidant mechanism. SDH could probably be a new target for drug discovery to alleviate myocardial I/R injury.


Assuntos
Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Miocárdio/citologia , Miocárdio/metabolismo , Oxigênio/metabolismo , Succinato Desidrogenase/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Domínio Catalítico , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ácidos Cumáricos/metabolismo , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Simulação de Acoplamento Molecular , Ratos , Espécies Reativas de Oxigênio/metabolismo , Succinato Desidrogenase/química , Ácido Succínico/metabolismo
20.
Carbohydr Polym ; 216: 1-16, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047045

RESUMO

Sinapic acid (SA) is a plant-derived phenolic compound known for its multiple biological properties, but its role in the promotion of bone formation is not yet well-studied. Moreover, the delivery of SA is hindered by its complex hydrophobic nature, limiting its bioavailability. In this study, we fabricated a drug delivery system using chitosan nanoparticles (nCS) loaded with SA at different concentrations. These were incorporated into polycaprolactone (PCL) fibers via an electrospinning method. nCS loaded with 50 µM SA in PCL fibers promoted osteoblast differentiation. Furthermore, SA treatment activated the osteogenesis signaling pathways in mouse mesenchymal stem cells. A critical-sized rat calvarial bone defect model system identified that the inclusion of SA into PCL/nCS fibers accelerated bone formation. Collectively, these data suggest that SA promoted osteoblast differentiation in vitro and bone formation in vivo, possibly by activating the TGF-ß1/BMP/Smads/Runx2 signaling pathways, suggesting SA might have therapeutic benefits in bone regeneration.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Quitosana/química , Ácidos Cumáricos/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Poliésteres/química , Animais , Diferenciação Celular/efeitos dos fármacos , Quitosana/toxicidade , Ácidos Cumáricos/toxicidade , Portadores de Fármacos/toxicidade , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Nanopartículas/toxicidade , Osteogênese/efeitos dos fármacos , Poliésteres/toxicidade , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Crânio/efeitos dos fármacos , Crânio/patologia , Resistência à Tração
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