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1.
PLoS One ; 15(4): e0231403, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271832

RESUMO

A flavone luteolin has various health-promoting activities. Several studies reported that high dose of luteolin activates the Nrf2/ARE pathway in the liver. However, the effect of the low dose of luteolin that can be taken from a dietary meal on the Nrf2 activation remain unclear. It is expected that the flavonoid metabolism possesses a circadian rhythm, since nutritional metabolism processes daily cycle. In this study we investigated whether an administration affects the Nrf2 activation. ICR mice were orally administered 0.01-10 mg/kg body weight of luteolin once a day for 7 days at two time-points: at the start of active phase (ZT12) or at that of inactive phase (ZT0). Luteolin increased the nuclear translocation of Nrf2, resulting in the increases in its target gene products HO-1 and NQO1 at ZT12 but not at ZT0. The expression level of Nrf2 was lower at ZT12 than at ZT0 in the liver. We also found that the level of luteolin aglycon in the plasma is higher at ZT12 than at ZT0. These results suggest that the low dose of luteolin can activate Nrf2 pathway and the aglycon form of luteolin may mainly contribute to activate the Nrf2 pathway at ZT12 in the liver.


Assuntos
Fígado/efeitos dos fármacos , Luteolina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Relógios Biológicos/genética , Núcleo Celular/metabolismo , Heme Oxigenase-1/metabolismo , Fígado/metabolismo , Luteolina/sangue , Masculino , Camundongos , Camundongos Endogâmicos ICR , NAD(P)H Desidrogenase (Quinona)/metabolismo , Regulação para Cima/efeitos dos fármacos
2.
Ecotoxicol Environ Saf ; 196: 110540, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32251950

RESUMO

By testing time-dependent IC50 of luteolin against Microcystis growth, this study revealed 6.5 mg/L as nearly IC50 value during prolonged stress until day 14, and explored chlorophyll-a (CLA) and phycobiliproteins (PBPs) contents, antioxidant responses and microcystin (MC)-production/-release dynamics at rising luteolin doses (0.5~2-fold IC50). Growth inhibition ratio (GIR) generally rose at rising luteolin dose, while at each dose GIR firstly increased and then leveled off or dropped. In early stage, CLA, allophycocyanin (APC), phycoerythrin (PE) and glutathione (GSH) contents, and superoxide dismutase (SOD) and catalase (CAT) activities, were increasingly stimulated at rising luteolin dose to enhance energy yield and antioxidant defense, but Microcystis was damaged more severely at rising dose, due to stress-repair imbalance. Such more severe damage in early stage, coupled with stronger PBPs-inhibition in mid-late stage, at rising dose could jointly account for rising GIR at rising dose. The CAT/GSH-stimulation persisting until late stage could alleviate cell damage in late stage, which explained for why GIR no longer increased in late stage at each luteolin dose. Besides, more MCs were produced and retained in cell to exert protective roles against luteolin-stress in early stage, but intracellular MCs decreased following inhibited MC-production by prolonged stress to decrease cell protectant. Extracellular MCs detection showed that less MCs amount existed in water phase than control along luteolin-stress, implying luteolin as eco-friendly algaecide with promising potential to remove MPM blooms and MC-risks. This is the first study to reveal the effect of various luteolin doses on MC-production/release and PBP-synthesis dynamics of Microcystis during prolonged stress. The findings shed novel views in anti-algal mechanisms of luteolin, and provided direct evidence for luteolin applied as safe agent to remediate Microcystis-dominant blooms.


Assuntos
Luteolina/farmacologia , Microcistinas/biossíntese , Microcystis/efeitos dos fármacos , Antioxidantes/metabolismo , Catalase/metabolismo , Clorofila A/metabolismo , Glutationa/metabolismo , Microcystis/enzimologia , Microcystis/crescimento & desenvolvimento , Microcystis/metabolismo , Ficobiliproteínas/metabolismo , Ficocianina/metabolismo , Superóxido Dismutase/metabolismo
3.
Anticancer Res ; 40(2): 723-731, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014914

RESUMO

BACKGROUND/AIM: MicroRNAs (miRNAs) play regulatory roles in pancreatic ductal adenocarcinoma (PDAC). However, it is still required to identify the function of miRNA-301-3p in pancreatic cancer cells. MATERIALS AND METHODS: Effects of luteolin on cell growth, TRAIL cytotoxicity, and miR-301-3p levels were evaluated. The role of miRNA-301-3p in regulating cell proliferation, target gene expression, and TRAIL cytotoxicity were studied. RESULTS: The levels of miR-301-3p were down-regulated in PANC-1 cells exposed to luteolin, which inhibits the growth of PANC-1 cells and sensitizes cells to TRAIL. The knockdown of miR-301-3p attenuates cell proliferation and enhances TRAIL cytotoxicity. In addition, caspase-8 was directly targeted by miR-301-3p. CONCLUSION: Our findings unveil a critical biological function of miR-301-3p in regulating cell proliferation and elevating an antiproliferative effect of TRAIL on cancer cells. Our observation of miR-301-3p/caspase-8 relationship can also serve to clarify the role of miR-301-3p in other cancer types and related diseases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Caspase 8/metabolismo , Luteolina/farmacologia , MicroRNAs/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Carcinoma Ductal Pancreático/genética , Caspase 8/genética , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Técnicas de Silenciamento de Genes , Humanos , Luteolina/administração & dosagem , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Proteínas Recombinantes/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/administração & dosagem , Transfecção
4.
Exp Mol Pathol ; 113: 104370, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31917965

RESUMO

Luteolin has been reported to impede migration via repressing tumor-associated macrophage-secreted chemokine ligand 2 expression. However, it's still unexplored whether luteolin represses the metastasis progression of leukemia cells via regulating the expression of C-X-C motif chemokine receptor 4 (CXCR4). Jurkat cells were stimulated by lactacystin and chloroquine after luteolin preincubation. C-X-C motif chemokine ligand 12 (CXCL12) was applied to induce migration of Jurkat cells after the cells were pre-incubated with luteolin (50, 100, 150, and 200 µM). CXCR4 was quantified by Western blot assay. Next, cell counting kit-8 (CCK-8) was used to detect cell viability. Apoptotic cells were observed with flow cytometry after staining. Migration assay was performed using a modified Boyden's chamber. We found that luteolin repressed CXCR4 expression at mRNA levels and restrained CXCL12-induced proliferation as well as migration. Furthermore, luteolin facilitated Jurkat cells apoptosis which was associated with the cleavage of caspase. Additionally, luteolin impeded the phosphorylated expression of PI3K, AKT, and ERK1 which was enhanced by CXCL12. In conclusion, luteolin exhibited anti-proliferation and anti-metastasis functions in CXCL12-treated Jurkat cells and inactivated PI3K/AKT and ERK signaling pathways via repressing the transcription of CXCR4.


Assuntos
Movimento Celular/efeitos dos fármacos , Quimiocina CXCL12/farmacologia , Luteolina/farmacologia , Receptores CXCR4/genética , Transcrição Genética/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/genética , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Células Jurkat , Luteolina/química , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores CXCR4/metabolismo
5.
J Food Sci ; 85(2): 298-305, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31957877

RESUMO

Antioxidant activity of the natural flavonoids luteolin and catechin, which shows inconsistent comparative results in literature, was extensively evaluated as affected by the 1,4-pyrone moiety and 3-OH group. Catechin and luteolin were compared to the synthetic antioxidant-butylated hydroxytoluene for their 2,2-diphenyl-1-picrylhydrazyl (DPPH● ) scavenging activity in polar protic and aprotic solvents and ferric reducing-antioxidant power (FRAP). Moreover, their effect on lipid oxidation kinetics of canola and olive oil triacylglycerols as well as their oil-in-water (O/W) emulsions, in addition to oil stability indices (OSIs), was evaluated. In the DPPH● assay, catechin's 3-OH group led to lower IC50 values than luteolin's 1,4-pyrone moiety in acetone (3.4 µM compared with 9.4 µM), while there was no significant difference in methanol (IC50 = approximately 18.3 µM) or tetrahydrofuran (IC50 = approximately 27.2 µM). The FRAP test indicated a higher reducing power for catechin than for luteolin (689.4 µM compared with 573.1 µM). The antioxidants showed various performances in the oil triacylglycerols and their O/W emulsions due predominantly to the interfacial phenomena. A better OSI was found for catechin than for luteolin (20.0 to 52.7 hr compared with 3.5 to 4.2 hr) in Rancimat test.


Assuntos
Antioxidantes/química , Catequina/química , Luteolina/química , Antioxidantes/farmacologia , Catequina/farmacologia , Cinética , Luteolina/farmacologia , Oxirredução , Relação Estrutura-Atividade
6.
Cancer Sci ; 111(4): 1165-1179, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31994822

RESUMO

Luteolin is a natural flavonoid with strong anti-oxidative properties that is reported to have an anti-cancer effect in several malignancies other than bladder cancer. In this study, we describe the effect of luteolin on a human bladder cancer cell line, T24, in the context of the regulation of p21, thioredoxin-1 (TRX1) and the mechanistic target of rapamycin (mTOR) pathway. Luteolin inhibited cell survival and induced G2/M cell-cycle arrest, p21 upregulation and downregulation of phospho(p)-S6, which is downstream of mTOR signaling. Luteolin also upregulated TRX1 and reduced intracellular reactive oxygen species production. In a subcutaneous xenograft mouse model using the rat bladder cancer cell line, BC31, tumor volumes were significantly decreased in mice orally administered luteolin compared to control. Immunohistochemical analysis revealed that increased p21 and decreased p-S6 expression were induced in the luteolin treatment group. Moreover, in another in vivo N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder cancer model, the oral administration of luteolin led to a trend of decreased bladder tumor dimension and significantly decreased the Ki67-labeling index and p-S6 expression. Furthermore, the major findings on the metabolism of luteolin suggest that both plasma and urine luteolin-3'-O-glucuronide concentrations are strongly associated with the inhibition of cell proliferation and mTOR signaling. Moreover, a significant decrease in the squamous differentiation of bladder cancer is attributed to plasma luteolin-3'-glucuronide concentration. In conclusion, luteolin, and in particular its metabolized product, may represent another natural product-derived therapeutic agent that acts against bladder cancer by upregulating p21 and inhibiting mTOR signaling.


Assuntos
Luteolina/farmacologia , Serina-Treonina Quinases TOR/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Proteínas rho de Ligação ao GTP/genética , Animais , Apoptose/efeitos dos fármacos , Butilidroxibutilnitrosamina/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Antígeno Ki-67/genética , Luteolina/metabolismo , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Transdução de Sinais/efeitos dos fármacos , Tiorredoxinas/genética , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
J Chromatogr A ; 1614: 460727, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31780080

RESUMO

The research of natural active substances is facing the problems of low separation efficiency and active component loss due to the complex composition of natural extracts. In this study, a strategy based on liquid-liquid-refining extraction and high-speed counter-current chromatography was established to solve this problem. Separation of an active compound with the α-amylase inhibitory activity from Taraxacum mongolicum Hand. -Mazz. was presented as an example. The ethyl acetate extract (FA) from T. mongolicum exhibited the potential effect on α-amylase and was divided into 8 fractions (FB-FI) by liquid-liquid-refining extraction. The results showed that the activity of FE was higher than the others. According to the results of liquid-liquid-refining extraction, a two-phase solvent system with a slightly higher polarity was selected to separate the fraction by HSCCC, and 110 mg of compound was separated from 900 mg FA using the model of consecutive separation. The compound was identified as luteolin by 1H NMR and 13C NMR. The IC50 of luteolin against α-amylase was 42.33±0.82 µg/mL. Then, molecular docking was introduced to study the relationship between the activity and the structure. The results showed that luteolin enfolded in the catalytic site of α-amylase through hydrogen bonds, van der Waals force and hydrophobic interaction, thus inhibiting the activity of the enzyme.


Assuntos
Bioensaio , Técnicas de Química Analítica/métodos , Distribuição Contracorrente , Extração Líquido-Líquido , Luteolina/farmacologia , Extratos Vegetais/farmacologia , Taraxacum/química , Acetatos/química , Ativação Enzimática/efeitos dos fármacos , Concentração Inibidora 50 , Luteolina/química , Luteolina/isolamento & purificação , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , alfa-Amilases/metabolismo
8.
Ecotoxicol Environ Saf ; 187: 109851, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31670181

RESUMO

Cadmium is a heavy metal pollutant that has been reported to cause oxidative stress, apoptosis, and autophagy in cells, while the flavone isoorientin is a traditional Chinese medicine extract that has proven antioxidant and anti-inflammatory properties. Accordingly, in this study we used the rat proximal tubular cell line NRK-52E and primary rat proximal tubular (rPT) cells as models to investigate the effects of isoorientin against Cadmium-induced cell injury and the mechanism of these effects. Comet assay, Western blot, flow cytometry, immunofluorescence, and transmission electron microscopy were used to evaluate cell damage and cell-cycle-related protein expression. Furthermore, real-time cell analysis, cell-counting kit-8, and ELISA were used to investigate the role of isoorientin in Cadmium-induced cell injury. The results revealed that treatment of rat renal tubular epithelial cells with 2.5 µM Cd for 12 h resulted in DNA damage and G0/G1 cell cycle arrest, while isoorientin attenuated this Cd-induced damage.


Assuntos
Antioxidantes/farmacologia , Cádmio/toxicidade , Dano ao DNA/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Luteolina/farmacologia , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos
9.
Biomed Pharmacother ; 121: 109681, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31810125

RESUMO

OBJECTIVES: Cynaroside (CYN) is the predominant derivative of luteolin in aerial parts of Bidens tripartita which has been used in folk medicine as a diaphoretic, diuretic, antiseptic and anti-inflammatory agent. In our study, alginate (ALG), which is an anionic polymer with bioadhesive properties, was used as a CYN carrier, and multiple hydrogel formulations were created. Additionally, the present study evaluated the in vivo anti-inflammatory and anti-allergic activities of all preparations. METHODS: Novel gel formulations as topical carriers for CYN obtained from B. tripartita were developed and characterized. The bioadhesive properties of the designed preparations were also evaluated in an ex vivo model using the skin of hairless mice. In vitro CYN release from all formulations was examined and analysed by HPLC. Histopathological evaluation of mouse skin sections stained with H&E after carrageenan and oxazolone administration was also carried out. In addition, the influence of CYN on cell proliferation was examined by the PCNA staining method. RESULTS: The results showed that 10 % CYN inhibited the release of anti-inflammatory mediators, and both tested concentrations, which included 5 % and 10 % (2 mg and 20 mg CYN per site, respectively), reduced oxazolone-induced ear swelling. Histopathological examination of the samples revealed a marked reduction in paw skin and ear tissue inflammation and in inflammatory infiltrates. The influence of CYN on cell proliferation was examined by the PCNA staining method, and the staining and distribution of PCNA-immunoreactive (PCNA-IR) cells were observed. After the application of the 5 % and 10 % hydrogels, the investigated samples showed decreased nuclear immunoreactivity to PCNA, which was similar to that of the control. Moreover, after application of the placebo formulation, fewer PCNA-IR cells were also observed. CONCLUSION: The obtained data suggest that the topical application of CYN significantly reduces the number of T cells, mast cells and histiocytes in mouse skin with inflammation or atopic dermatitis.


Assuntos
Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Composição de Medicamentos , Glucosídeos/farmacologia , Hidrogéis/química , Luteolina/farmacologia , Animais , Antialérgicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Edema/tratamento farmacológico , Masculino , Camundongos Endogâmicos C57BL , Oxazolona , Antígeno Nuclear de Célula em Proliferação/metabolismo
10.
Molecules ; 24(24)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31817382

RESUMO

Tectaria coadunata, an ethnomedicinal fern used in Nepal to treat a large number of diseases, has been poorly studied with regard to its phytochemical composition and possible bioactivity. This study was performed with the aim of supporting traditional medicine as a new source of bioactive constituents. Phytochemical compositions of methanol extracts were determined by nuclear magnetic resonance (NMR), liquid chromatography-diode array detector-mass spectrophotometry (LC-DAD-MS), and liquid chromatography-fluorescence-mass spectrometry. Quali-quantitative data revealed large amount of procyanidins, mainly of the A-type, as well as eriodictyol-7-O-glucuronide and luteolin-7-O-glucoronide as main constituents. The antioxidant, cytotoxic, and inhibitory activity of five enzymes that are implicated in human diseases was evaluated for the extract and fractions. High free-radical scavenging activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays and inhibitory activities against cholinesterases and tyrosinase were observed. Furthermore, a moderate cytotoxic effect was observed on the 2008 and BxPC3 cell lines. Overall results showed potential usefulness of this fern as a source of phytochemicals for pharmaceutical uses.


Assuntos
Antioxidantes , Bioensaio , Citotoxinas , Gleiquênias/química , Luteolina , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Citotoxinas/química , Citotoxinas/farmacologia , Humanos , Luteolina/química , Luteolina/farmacologia , Nepal , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia
11.
Int J Mol Sci ; 20(19)2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31590417

RESUMO

The Niemann-Pick C1-like 1 (NPC1L1) protein is a cholesterol transporter that is expressed in the small intestine. This report describes the discovery of NPC1L1, its transport properties, and the inhibitory effects of polyphenols on NPC1L1. NPC1L1 was identified in 2004 while searching for ezetimibe molecular targets. Excessive synthesis of cholesterol results in hyperlipidemia, which increases the amount of bile cholesterol excreted into the duodenum. The inhibition of NPC1L1 decreases blood cholesterol because food and bile cholesterol are also absorbed from NPC1L1 in the intestine. Some polyphenols, particularly luteolin, have been reported as NPC1L1-mediated anti-dyslipidemia constituents. Luteolin affects NPC1L1 through two mechanisms. Luteolin directly inhibits NPC1L1 by binding to it, which occurs in a short timeframe similar to that for ezetimibe. The other mechanism is the inhibition of NPC1L1 expression. Luteolin reduced the binding of Sterol-regulatory element-binding protein 2 (SREBP2) in the promoter region of the NPC1L1 gene and decreased mRNA levels of SREBP2 and hepatocyte nuclear factor 4α. These data suggest that luteolin decreases the expression of NPC1L1 through regulation of transcription factors. This review also explores the effect of other polyphenols on NPC1L1 and hypercholesterolemia.


Assuntos
Regulação para Baixo , Hipercolesterolemia/tratamento farmacológico , Proteínas de Membrana Transportadoras/metabolismo , Polifenóis/administração & dosagem , Transporte Biológico , Fator 4 Nuclear de Hepatócito/metabolismo , Humanos , Hipercolesterolemia/genética , Hipercolesterolemia/metabolismo , Luteolina/administração & dosagem , Luteolina/farmacologia , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/genética , Polifenóis/farmacologia , Regiões Promotoras Genéticas , Ligação Proteica/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
12.
Pharmacology ; 104(5-6): 296-302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587003

RESUMO

INTRODUCTION: Cynaroside is a biological component isolated from Lonicera japonica Thunb, and it possesses numerous pharmacological activities. However, whether cynaroside affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. The purpose of this study was to investigate the effects of cynaroside on 8 major CYP isoforms in human liver microsomes (HLMs). METHODS: In this study, the inhibitory effects of cynaroside on the 8 human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using HLMs. RESULTS: The results showed that cynaroside inhibited the activity of CYP1A2, 3A4, and 2C9, with IC50 values of 21.74, 15.88, and 16.58 µmol/L, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that cynaroside was not only a noncompetitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP1A2 and 2C9, with Ki values of 7.33, 11.60, and 8.09 µmol/L, respectively. In addition, cynaroside is a time-dependent inhibitor for CYP3A4 with Kinact/KI value of 0.049/11.62 µmol/L-1min-1. CONCLUSION: The in vitro studies of cynaroside with CYP isoforms indicate that cynaroside has the potential to cause pharmacokinetic drug interactions with other coadministered drugs metabolized by CYP1A2, 3A4, and 2C9. Further clinical studies are needed to evaluate the significance of this interaction.


Assuntos
Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Glucosídeos/farmacologia , Luteolina/farmacologia , Interações Medicamentosas , Humanos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia
13.
Biol Pharm Bull ; 42(9): 1446-1449, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474706

RESUMO

During the process of skin regeneration following a skin injury, de novo hair follicle regeneration is initiated after wounding; however, these regenerated hairs are mostly unpigmented. The activation of epidermal melanocyte stem cells and their differentiation into regenerating hair follicles have been shown to be necessary for the pigmented hair regeneration after wounding. To determine the role of flavonoids in the regeneration of pigmented hairs, we applied the candidate flavonoids to the regenerating hair follicles after wounding and identified the flavonoid species that maximally induced pigmented hair regeneration. Flavonoids with two OH groups in the B-ring, such as sterubin, luteolin, and hydroxygenkwanin, showed promising effects in regenerating black pigmented hairs, while those with one OH group in the B-ring showed no significant change. Thus, flavonoids with two OH groups in their B-ring could be studied further as potential wound healing agents with the ability to regenerate pigmented hair.


Assuntos
Flavonoides/farmacologia , Cor de Cabelo , Folículo Piloso/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Pele/lesões , Cicatrização/efeitos dos fármacos , Animais , Células Epidérmicas/efeitos dos fármacos , Células Epidérmicas/fisiologia , Flavonoides/química , Folículo Piloso/fisiologia , Luteolina/química , Luteolina/farmacologia , Melanócitos/efeitos dos fármacos , Melanócitos/fisiologia , Camundongos Endogâmicos C57BL , Pele/efeitos dos fármacos , Relação Estrutura-Atividade
14.
Mol Cells ; 42(9): 672-685, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31486328

RESUMO

Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygenglucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation.


Assuntos
Carbonil Redutase (NADPH)/metabolismo , Transplante de Fígado , Fator 2 Relacionado a NF-E2/metabolismo , Traumatismo por Reperfusão/terapia , Regulação para Cima , Adulto , Oxirredutases do Álcool/genética , Animais , Biópsia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Glucose/deficiência , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/patologia , Doadores Vivos , Luteolina/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Oxigênio , Transdução de Sinais/efeitos dos fármacos , Transcrição Genética/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
15.
Cell Mol Biol (Noisy-le-grand) ; 65(6): 91-95, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31472053

RESUMO

Osteoarthritis (OA) is a degenerative joint disease usually seen in the elderly, which incidence increases with age. Its pathogenesis and underlying mechanism are still unclear. The disease severely affects the physical health and life quality of patients, thereby constituting a huge economic burden to family and society. Luteolin (LUT) is a natural flavonoid with multiple pharmacological properties. Many plants containing LUT have been applied in the treatment of several inflammation-related diseases due the relatively strong anti-inflammatory effects of LUT. The present study investigated the influence of LUT on cell apoptosis and inflammatory reactions in cartilage of OA guinea pigs, and its underlying mechanism. It was found that LUT effectively inhibited proliferation of OA cartilage cells, down-regulated the expressions of JNK and p38MAPK in cartilage cells of OA, and downregulated NO, TNF-α and IL-6. Thus, it alleviated inflammatory reactions, protected cartilage cells, and delayed cartilage degeneration.


Assuntos
Apoptose/efeitos dos fármacos , Condrócitos/enzimologia , Condrócitos/patologia , Luteolina/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteoartrite/enzimologia , Osteoartrite/patologia , Animais , Osso e Ossos/patologia , Cartilagem/patologia , Proliferação de Células/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Cobaias , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Articulações/patologia , Lipopolissacarídeos , Luteolina/química
16.
Artigo em Inglês | MEDLINE | ID: mdl-31484378

RESUMO

Antialgal compounds from plants have been identified as promising candidates for controlling harmful algal blooms (HABs). In our previous study, luteolin-7-O-glucuronide was used as a promising algistatic agent to control Phaeocystis globosa (P. globose) blooms; however, its antialgal mechanism on P. globosa have not yet been elaborated in detail. In this study, a liquid chromatography linked to tandem mass spectrometry (LC-MS/MS)-based untargeted metabolomic approach was used to investigate changes in intracellular and extracellular metabolites of P. globosa after exposure to luteolin-7-O-glucuronide. Significant differences in intracellular metabolites profiles were observed between treated and untreated groups; nevertheless, metabolic statuses for extracellular metabolites were similar among these two groups. For intracellular metabolites, 20 identified metabolites showed significant difference. The contents of luteolin, gallic acid, betaine and three fatty acids were increased, while the contents of α-Ketoglutarate and acetyl-CoA involved in tricarboxylic acid cycle, glutamate, and 11 organic acids were decreased. Changes in those metabolites may be induced by the antialgal compound in response to stress. The results revealed that luteolin played a vital role in the antialgal mechanism of luteolin-7-O-glucuronide on P. globosa, because luteolin increased the most in the treatment groups and had strong antialgal activity on P. globosa. α-Ketoglutarate and acetyl-CoA were the most inhibited metabolites, indicating that the antialgal compound inhibited the growth through disturbed the tricarboxylic acid (TCA) cycle of algal cells. To summarize, our data provides insights into the antialgal mechanism of luteolin-7-O-glucuronide on P. globosa, which can be used to further control P. globosa blooms.


Assuntos
Haptófitas/efeitos dos fármacos , Herbicidas/farmacologia , Luteolina/farmacologia , Cromatografia Líquida , Haptófitas/crescimento & desenvolvimento , Haptófitas/metabolismo , Luteolina/metabolismo , Metabolômica , Espectrometria de Massas em Tandem
17.
Molecules ; 24(16)2019 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-31426583

RESUMO

The principle of animal wellbeing, which states that animals should be free from pain, injury, and disease, is difficult to maintain, because microorganisms are most frequently found to be resistant or multi-resistant to drugs. The secondary metabolites of plants are an alternative for the treatment of these microorganisms. The aim of this work was to determine the antibacterial effect of Salix babylonica L. hydroalcoholic extract (SBHE) against Escherichia coli, Staphylococcus aureus and Listeria monocytogenes, and identify the compounds associated with the activity. The SBHE showed activity against the three strains, and was subjected to a bipartition, obtaining aqueous fraction (ASB) with moderate activity and organic fraction (ACSB) with good activity against the three strains. The chromatographic separation of ACSB, allowed us to obtain ten fractions (F1AC to F10AC), and only three showed activity (F7AC, F8AC and F10AC). In F7AC, five compounds were identified preliminary by GC-MS, in F8AC and F10AC were identified luteolin (1) and luteolin 7-O-glucoside (2) by HPLC, respectively. The best antibacterial activity was obtained with F7AC (Listeria monocytogenes; MIC: 0.78 mg/mL, MBC: 0.78 mg/mL) and F8AC (Staphylococcus aureus; MIC: 0.39 mg/mL; MBC: 0.78 mg/mL). The results indicated that the compounds obtained from SBHE can be used as an alternative treatment against these microorganisms and, by this mechanism, contribute to animal and human health.


Assuntos
Antibacterianos/química , Flavonoides/química , Luteolina/química , Salix/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Cromatografia Líquida de Alta Pressão , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Etanol/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/crescimento & desenvolvimento , Luteolina/isolamento & purificação , Luteolina/farmacologia , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Solventes/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Água/química
18.
Artif Cells Nanomed Biotechnol ; 47(1): 3265-3271, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31368817

RESUMO

Luteolin is a representative of natural flavonoid that has anti-tumour properties. This study designed to check its impact on breast cancer and the underlying mechanisms. MDA-MB-453 and MCF-7 cells were administrated with luteolin and the following techniques were carried out: CCK-8 assay, FITC-PI double-staining and Western blot. qRT-PCR analysis was utilized to see the effects of luteolin on miR-203 expression. Besides, miR-203 expression was silenced by transfection with specific inhibitor. Luteolin remarkably declined MDA-MB-453 and MCF-7 cells viability and accelerated apoptosis which accompanied by Bax up-regulation, Bcl-2 down-regulation and Caspase-3 cleavage. Also, luteolin impeded TGFß1-induced EMT, as evidenced by the decreased levels of Vimentin, Zeb1 and N-cadherin, as well as the increased level of E-cadherin. miR-203 was highly expressed in 22 pair of breast cancer tissues than the matched paracancerous tissues. Luteolin could elevate miR-203 level. Besides, luteolin's anti-tumour effects were partially eliminated by miR-203 silence. Further, luteolin inhibited Ras/Raf/MEK/ERK signalling, while the inhibitory effects were flattened by miR-203 silence. Luteolin significantly reduced breast cancer cells growth and EMT. Luteolin exerted its anti-tumour effects possibly involved the elevated expression of miR-203 and the inhibited Ras/Raf/MEK/ERK signalling.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Luteolina/farmacologia , MicroRNAs/genética , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células MCF-7 , Quinases raf/metabolismo , Proteínas ras/metabolismo
19.
Drug Des Devel Ther ; 13: 2009-2019, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354246

RESUMO

Background: miR-29a, a downstream factor of Wnt/ß-catenin signaling, promotes the activity of the Wnt/ß-catenin signaling in a positive feedback loop. Our previous work showed that 5,7,3',4'-tetramethoxyflavone (TMF), a major constituent from Murraya exotica L., exhibited chondroprotective activity by inhibiting the activity of Wnt/ß-catenin signaling. Purpose: To investigate whether TMF showed the inhibitory effects on miR-29a/ß-catenin signaling by up regulation of Foxo3a expression. Methods: Rat knee OA models were duplicated by using Hulth's method. TMF (5 µg/mL and 20 µg/mL) was used for administration to cultured cells, which were isolated from the rat cartilages. Analysis of chondrocytes apoptosis, gene expression, and protein expression were conducted. In addition, miR-29a mimics and pcDNA3.1(+)-Foxo3a vector were used for transfection, luciferase reporter assay for detecting the activity of Wnt/ß-catenin signaling, and co-immunoprecipitation for determining proteins interaction. Results: TMF down regulated miR-29a/ß-catenin signaling activity and cleaved caspase-3 expression and up regulated Foxo3a expression in OA rat cartilages. In vitro, miR-29a mimics down regulated the expression of Foxo3a and up regulated the activity of Wnt/ß-catenin signaling and cleaved caspase-3 expression. TMF ameliorated miR-29a/ß-catenin-induced chondrocytes apoptosis by up regulation of Foxo3a expression. Conclusion: TMF exhibited chondroprotective activity by up regulating Foxo3a expression and subsequently inhibiting miR-29a/Wnt/ß-catenin signaling activity.


Assuntos
Condrócitos/efeitos dos fármacos , Proteína Forkhead Box O3/metabolismo , Luteolina/farmacologia , MicroRNAs/antagonistas & inibidores , Osteoartrite/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/antagonistas & inibidores , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Condrócitos/metabolismo , Condrócitos/patologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Luteolina/administração & dosagem , MicroRNAs/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Ratos , Regulação para Cima/efeitos dos fármacos , beta Catenina/metabolismo
20.
Neurotoxicology ; 74: 252-263, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31362009

RESUMO

Cobalt (Co) intoxication arising from occupational exposures and ion release from metal implants has been associated with neurological alterations such as cognitive decline, incoordination and depression. The present study evaluated the mechanisms of neuro-protection exerted by Luteolin (Lut; 100 mg/kg) and Gallic acid (GA; 120 mg/kg) in Wistar rats exposed to cobalt chloride (CoCl2) at 150 mg/kg for 7 consecutive days. Results indicate that CoCl2 induced neuro-behavioural deficits specifically by decreasing exploratory activities of CoCl2-exposed rats, increased anxiety, as well as significant reduction in hanging latency. Co-treatment with Lut or GA, however, restored these parameters to values near those of normal controls. Moreover, Lut and GA prevented CoCl2-induced increases in hydrogen peroxide (H2O2), malondialdehyde (MDA) and nitric oxide (NO) in the brain, while also restoring the activities of acetylcholinesterase, glutathione S-transferase (GST) and superoxide dismutase (SOD). In addition, Lut and GA produced significant reversal of CoCl2-induced elevation in levels of serum Interleukin 1 beta (IL-1ß) and Tumor necrosis factor (TNFα). Meanwhile, immunohistochemistry revealed increased astrocytic expression of glial fibrillary acidic protein (GFAP), with intense calbindin (CB) D-28k staining and pronounced dendrites in the Purkinje cells. In contrast, the CoCl2 group was characterized by decreased number of neurons expressing CB and dendritic loss. Taken together, mechanisms of luteolin and/or gallic acid protection against Co toxicity involved restoration of Ca2+ homeostasis, acetylcholinesterase and antioxidant enzyme activities, as well as inhibition of lipid peroxidation in the brain.


Assuntos
Comportamento Animal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Cobalto/toxicidade , Ácido Gálico/farmacologia , Luteolina/farmacologia , Fármacos Neuroprotetores/farmacologia , Acetilcolinesterase/metabolismo , Animais , Ansiedade/induzido quimicamente , Ansiedade/prevenção & controle , Ansiedade/psicologia , Astrócitos/metabolismo , Citocinas/sangue , Dendritos/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Células de Purkinje/efeitos dos fármacos , Ratos , Ratos Wistar
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