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1.
J Ethnopharmacol ; 283: 114666, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592338

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ervatamia coronaria, a popular garden plant in India and some other parts of the world is known traditionally for its anti-inflammatory and anti-cancer properties. The molecular bases of these functions remain poorly understood. AIM OF THE STUDY: Efficacies of the existing therapies for colorectal cancer (CRC) are limited by their life-threatening side effects and unaffordability. Therefore, identifying a safer, efficient, and affordable therapeutic is urgent. We studied the anti-CRC activity of an alkaloid-rich fraction of E. coronaria leaf extracts (AFE) and associated underlying mechanism. MATERIALS AND METHODS: Activity guided solvant fractionation was adopted to identify the activity in AFE. Different cell lines, and tumor grown in syngeneic mice were used to understand the anti-CRC effect. Methodologies such as LCMS, MTT, RT-qPCR, immunoblot, immunohistochemistry were employed to understand the molecular basis of its activity. RESULTS: We showed that AFE, which carries about six major compounds, is highly toxic to colorectal cancer (CRC) cells. AFE induced cell cycle arrest at G1 phase and p21 and p27 genes, while those of CDK2, CDK-4, cyclin-D, and cyclin-E genes were downregulated in HCT116 cells. It predominantly induced apoptosis in HCT116p53+/+ cells while the HCT116p53-/- cells under the same treatment condition died by autophagy. Notably, AFE induced upregulation of AMPK phosphorylation, and inhibition of both of the mTOR complexes as indicated by inhibition of phosphorylation of S6K1, 4EBP1, and AKT. Furthermore, AFE inhibited mTOR-driven conversion of cells from reversible cell cycle arrest to senescence (geroconversion) as well as ERK activity. AFE activity was independent of ROS produced, and did not primarily target the cellular DNA or cytoskeleton. AFE also efficiently regressed CT26-derived solid tumor in Balb/c mice acting alone or in synergy with 5FU through inducing autophagy as a major mechanism of action as indicated by upregulation of Beclin 1 and phospho-AMPK, and inhibition of phospho-S6K1 levels in the tumor tissue lysates. CONCLUSION: AFE induced CRC death through activation of both apoptotic and autophagy pathways without affecting the normal cells. This study provided a logical basis for consideration of AFE in future therapy regimen to overcome the limitations associated with existing anti-CRC chemotherapy.

2.
Int J Mol Sci ; 22(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34576147

RESUMO

Drug-resistant Staphylococcus aureus is an imminent threat to public health, increasing the importance of drug discovery utilizing unexplored bacterial pathways and enzyme targets. De novo pyrimidine biosynthesis is a specialized, highly conserved pathway implicated in both the survival and virulence of several clinically relevant pathogens. Class I dihydroorotase (DHOase) is a separate and distinct enzyme present in gram positive bacteria (i.e., S. aureus, B. anthracis) that converts carbamoyl-aspartate (Ca-asp) to dihydroorotate (DHO)-an integral step in the de novo pyrimidine biosynthesis pathway. This study sets forth a high-throughput screening (HTS) of 3000 fragment compounds by a colorimetry-based enzymatic assay as a primary screen, identifying small molecule inhibitors of S. aureus DHOase (SaDHOase), followed by hit validation with a direct binding analysis using surface plasmon resonance (SPR). Competition SPR studies of six hit compounds and eight additional analogs with the substrate Ca-asp determined the best compound to be a competitive inhibitor with a KD value of 11 µM, which is 10-fold tighter than Ca-asp. Preliminary structure-activity relationship (SAR) provides the foundation for further structure-based antimicrobial inhibitor design against S. aureus.


Assuntos
Di-Hidro-Orotase/antagonistas & inibidores , Inibidores Enzimáticos/análise , Inibidores Enzimáticos/farmacologia , Ensaios de Triagem em Larga Escala , Bibliotecas de Moléculas Pequenas/análise , Bibliotecas de Moléculas Pequenas/farmacologia , Staphylococcus aureus/enzimologia , Domínio Catalítico , Di-Hidro-Orotase/química , Di-Hidro-Orotase/isolamento & purificação , Di-Hidro-Orotase/metabolismo , Inibidores Enzimáticos/química , Simulação de Acoplamento Molecular , Bibliotecas de Moléculas Pequenas/química , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade
3.
Comput Struct Biotechnol J ; 19: 3437-3450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194669

RESUMO

Pancreatic cancer remains one of the cancers with the poorest prognosis bearing an overall 5-year survival rate of about 5%. Efficient new chemotherapic drugs are still highly desired. Here, bruceine A, a quassinoid identified from the dried fruits of Brucea javanica (L.) Merr., displayed the most potent anti-proliferation activity against pancreatic cancer in vitro and in vivo. Phosphoproteomic analysis revealed p38α MAPK phosphorylation was involved in bruceine A's action in MIA PaCa-2 cells. Utilizing fortebio octet system and microscale thermophoresis, we found p38α MAPK had high affinity for bruceine A. Molecular docking and molecular dynamic simulations showed that bruceine A widely bound to residues (Leu171, Ala172, Met179, Thr180, Val183) in P-loop of p38α MAPK. Key determinants of bruceine A binding with P-loop of p38α MAPK were 19-C[bond, double bond]O, 22-CH3, 32-CH3, and 34-CH3. Taken together, our findings demonstrate that bruceine A binds directly to p38α MAPK, which can be used to probe the role of p38α MAPK phosphorylation in pancreatic cancer progression, and as a novel lead compound for pancreatic cancer therapy.

4.
J Nat Prod ; 84(4): 949-955, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33769037

RESUMO

Eleven pimarane-type diterpenoids were isolated from the tubers of Icacina oliviformis, including three new compounds, icacinlactone M (9), icacinlactone H 2-O-ß-d-glucopyranoside (10), and icacinlactone N 3-O-ß-d-glucopyranoside (11), together with an artifact of acrenol (8). Among the known structures, icacinlactone A (2), icacinlactone B (3), icacinlactone H (4), 12-hydroxyicacinlactone A (5), 14α-methoxyhumirianthol (6), and annonalide (7) are reported from I. oliviformis for the first time, whereas icacinol (1) has previously been found in this plant. Icacinol, 14α-methoxyhumirianthol, and annonalide displayed moderate cytotoxic activity in a panel of human cancer cell lines.


Assuntos
Abietanos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Magnoliopsida/química , Abietanos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Diterpenos , Humanos , Estrutura Molecular , Nigéria , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Tubérculos/química
5.
Phytochemistry ; 186: 112711, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33711738

RESUMO

Ten undescribed anthranoids, including three anthraquinone acetals as racemic mixtures, (±)-kenganthranol G-I, and seven prenylated anthranols, (±)-kenganthranol J-M and harunganol G-I, together with thirteen known compounds, were isolated from the stem bark of Harungana madagascariensis. The structures of (±)-kenganthranol G and (±)-kenganthranol J were confirmed by X-ray crystallography. (±)-Kenganthranol G was separated into (+)-kenganthranol G and (-)-kenganthranol G by chiral HPLC and their absolute configurations were established by electronic circular dichroism. (±)-Kenganthranol L displayed α-glucosidase inhibitory activity with an IC50 of 4.4 µM.


Assuntos
Clusiaceae , Antraquinonas , Estrutura Molecular
6.
Fitoterapia ; 150: 104846, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33588006

RESUMO

Four new compounds (1-4) were isolated from the stem bark of Entandrophragma angolense along with eleven known structures (5-15). The chemical structures were elucidated on the basis of spectroscopic and HRMS data, and the absolute configuration was established with the aid of electronic circular dichroism. Compound 5 displayed moderate cytotoxicity against MDA-MB-231, OVCAR3, MDA-MB-435, and HT29 cell lines, with IC50 values ranging from 2.0-5.9 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Limoninas/farmacologia , Meliaceae/química , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Limoninas/isolamento & purificação , Estrutura Molecular , Nigéria , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Plantas Medicinais/química , Triterpenos/isolamento & purificação
8.
Fitoterapia ; 144: 104612, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32437735

RESUMO

Four new unusual 19-nor-pimarane-type diterpenes were isolated from the tuber of Icacina trichantha (Icacinaceae, Oliv.). The structures were elucidated based on spectroscopic and HRMS analysis. The absolute configurations were determined by electronic circular dichroism. All four compounds are structural analogues of icacinol and humirianthol, but do not demonstrate the same cytotoxic activity. A plausible biogenetic pathway is proposed.


Assuntos
Abietanos/química , Magnoliopsida/química , Tubérculos/química , Abietanos/isolamento & purificação , Linhagem Celular Tumoral , Diterpenos , Humanos , Estrutura Molecular , Nigéria , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
9.
Chin J Nat Med ; 18(5): 385-392, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32451096

RESUMO

Three new indole alkaloids, flueindolines A-C (1-3), along with nine known alkaloids (4-12), were isolated from the fruits of Flueggea virosa (Roxb. ex Willd.) Voigt. Compounds 1 and 2 are two new fused tricyclic indole alkaloids possessing an unusual pyrido[1, 2-a]indole framework, and 3 presents a rare spiro (pyrrolizidinyl-oxindole) backbone. Their structures with absolute configurations were elucidated by means of comprehensive spectroscopic analysis, chemical calculation, as well as X-ray crystallography. Chiral resolution and absolute configuration determination of the known compounds 4, 10, and 11 were reported for the first time. The hypothetical biogenetical pathways of 1-3 were herein also proposed.


Assuntos
Medicamentos de Ervas Chinesas/química , Alcaloides Indólicos/química , Magnoliopsida/química , Cristalografia por Raios X , Frutas/química
10.
J Nat Prod ; 82(10): 2916-2924, 2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31618031

RESUMO

Phytochemical investigation of the leaves and bark of Psydrax subcordata has led to the isolation of six new iridoids, subcordatanols I-V (1-4 and 6) and 1-O-methylcrescentin I (5), along with two known analogues (7 and 8). Among them, subcordatanol I (1) is the first example of a 3,8-monoepoxy-iridoid featuring a caged 2-oxa-bicyclo[3.2.1]octane core. The absolute stereochemistry at C-4 of 3, 4, and 6 was established through their acid-catalyzed reaction products subcordatalactones A (3a), B (4a), and C (6a), respectively. Subcordatanols I (1) and II (2), as well as subcordatalactones A (3a) and B (4a), displayed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Enzyme kinetic studies indicated that 3a and 4a are competitive inhibitors. A molecular docking study is also reported.


Assuntos
Iridoides/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Rubiaceae/química , Iridoides/química , Iridoides/farmacologia , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular
11.
J Pharm Biomed Anal ; 170: 264-272, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-30947127

RESUMO

Bruceoside A, an abundant quassinoid glycoside in Fructus Bruceae, was chosen for the pharmacokinetic study. It is the first case report on the pharmacokinetic study of quassinoid glycosides so far. A sensitive, accurate, and repeatable UHPLC-MS/MS method was developed for the determination of bruceoside A and its major metabolite. The results showed bruceoside A could be transformed into the potent anticancer component brusatol in vivo, rather than its direct deglycosylated metabolite bruceosin. And the intestinal bacteria were proposed to take a potential role during such transformation. Based on the present study, it could be concluded that the quassinoid glycosides possessing weak activities in vitro could do contribution to the anticancer properties of Fructus Bruceae in vivo via transforming into more active metabolites.


Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/farmacocinética , Glicosídeos/farmacocinética , Quassinas/farmacocinética , Animais , Antineoplásicos Fitogênicos/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Glicosídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Quassinas/farmacologia , Espectrometria de Massas em Tandem/métodos
12.
Int J Mol Sci ; 20(4)2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30769917

RESUMO

The aim of this Special Issue on "Plant Natural Products for Human Health" is to compile a series of scientific reports to demonstrate the medicinal potential of plant natural products, such as in vitro and in vivo activities, clinical effects, mechanisms of action, structure-activity relationships, and pharmacokinetic properties. With the global trend growing in popularity for botanical dietary supplements and phytopharmaceuticals, it is hoped that this Special Issue would serve as a timely reference for researchers and scholars who are interested in the discovery of potentially useful molecules from plant sources for health-related applications.


Assuntos
Produtos Biológicos , Plantas Medicinais , Suplementos Nutricionais , Humanos , Fitoterapia/tendências
13.
Int J Mol Sci ; 19(9)2018 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-30149545

RESUMO

Rheumatoid arthritis (RA) is a chronic, debilitating illness characterized by painful swelling of the joints, inflammation of the synovial lining of the joints, and damage to cartilage and bone. Several anti-inflammatory and disease-modifying drugs are available for RA therapy. However, the prolonged use of these drugs is associated with severe side effects. Furthermore, these drugs are effective only in a proportion of RA patients. Hence, there is a need to search for new therapeutic agents that are effective yet safe. Interestingly, a variety of herbs and other natural products offer a vast resource for such anti-arthritic agents. We discuss here the basic features of RA pathogenesis; the commonly used animal models of RA; the mainstream drugs used for RA; the use of well-characterized natural products possessing anti-arthritic activity; the application of nanoparticles for efficient delivery of such products; and the interplay between dietary products and the host microbiome for maintenance of health and disease induction. We believe that with several advances in the past decade in the characterization and functional studies of natural products, the stage is set for widespread clinical testing and/or use of these products for the treatment of RA and other diseases.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite/tratamento farmacológico , Artrite/imunologia , Doenças Autoimunes/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Artrite/etiologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/etiologia , Artrite Reumatoide/patologia , Doenças Autoimunes/etiologia , Produtos Biológicos/farmacologia , Biomarcadores , Modelos Animais de Doenças , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos , Mediadores da Inflamação/metabolismo , Microbiota , Terapia de Alvo Molecular , Nanopartículas/química , Preparações de Plantas/farmacologia , Preparações de Plantas/uso terapêutico
14.
J Agric Food Chem ; 66(30): 7859-7872, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29996047

RESUMO

Momilactones are allelochemicals in rice and moss defense. Momilactone-like compounds are therefore considered important secondary metabolites for plant defense. They may serve as promising lead compounds for crop-friendly herbicides as well as antifungal and antibacterial agents. Many of these substances possess potent cytotoxicity property against cancer cell lines as well. The present paper is the first review on these versatile molecules, focusing on the structure, biological activity, chemical synthesis, and biosynthesis of the naturally occurring momilactone-like molecules reported from 1973 to 2017.


Assuntos
Agroquímicos/química , Diterpenos/química , Lactonas/química , Extratos Vegetais/química , Agroquímicos/farmacologia , Animais , Briófitas/química , Diterpenos/farmacologia , Humanos , Lactonas/farmacologia , Oryza/química , Oryza/metabolismo , Extratos Vegetais/farmacologia
15.
Phytother Res ; 32(4): 672-677, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29368404

RESUMO

The aim of this study was to determine the antimicrobial capacity, minimum inhibitory concentration (MIC), and cytotoxic effects of a Peganum harmala seed extract in comparison to 5.25% sodium hypochlorite (NaOCl). The oral pathogen Enterococcus faecalis was used to evaluate the antimicrobial capacity, and the MIC values were determined through serial dilution. Inhibition zones were measured in millimeter, and the data were analyzed statistically by analysis of variance and the Tukey HSD test. For cytotoxicity testing, P. harmala seed extract and 5.25% NaOCl solution were incubated with L929 fibroblast cells. After 1, 24, and 72 hr of incubation, cells were stained and the optical density determined with an enzyme-linked immunosorbent assay (ELISA) reader. Data were analyzed with Chi-Square statistical test. The significance level was set at p < .05. There was no significant difference between the antimicrobial capacity of 5.25% NaOCl and the P. harmala extract (p > .05; MIC 4 µg/ml). The Microculture Tetrazolium (MTT) assay test showed that the cytotoxic effects of the P. harmala extract were significantly lower than 5.25% NaOCl (p < .05). The results show that 5.25% NaOCl and P. harmala seed extract have similar antimicrobial activity against Enterococcus faecalis; but P. harmala, which shows reduced cytotoxicity, should be considered for further investigation as a safe, phytotherapeutic, intracanal irrigant.


Assuntos
Antibacterianos/uso terapêutico , Cromatografia Líquida/métodos , Cavidade Pulpar/efeitos dos fármacos , Desinfecção/métodos , Espectrometria de Massas/métodos , Peganum/metabolismo , Extratos Vegetais/uso terapêutico , Antibacterianos/farmacologia , Humanos , Extratos Vegetais/farmacologia
16.
Theranostics ; 8(21): 5945-5959, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30613273

RESUMO

The gut microbiota is increasingly recognized to influence brain function through the gut-brain axis. Albiflorin, an antidepressant natural drug in China with a good safety profile, is difficult to absorb and cannot be detected in the brain after oral administration. Accordingly, the antidepressant mechanism of albiflorin in vivo has not been elucidated clearly. Methods: We identified benzoic acid as the characteristic metabolite of albiflorin in vivo and in vitro, then discovered the roles of gut microbiota in the conversion of albiflorin by carboxylesterase. Pharmacodynamic and pharmacokinetic studies were performed for the antidepressant activities of albiflorin in animals, and the efficacy of benzoic acid in inhibiting D-amino acid oxidase (DAAO) in brain was further investigated. Results: We validated that gut microbiota transformed albiflorin to benzoic acid, a key metabolite in the intestine that could cross the blood-brain barrier and, as an inhibitor of DAAO in the brain, improved brain function and exerted antidepressant activity in vivo. Intestinal carboxylesterase was the crucial enzyme that generated benzoic acid from albiflorin. Additionally, the regulatory effect of albiflorin on the gut microbiota composition was beneficial to alleviate depression. Conclusion: Our findings suggest a novel gut-brain dialogue through intestinal benzoic acid for the treatment of depression and reveal that the gut microbiota may play a causal role in the pathogenesis and treatment of the central nervous system disease.


Assuntos
Antidepressivos/administração & dosagem , Encéfalo/metabolismo , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Microbioma Gastrointestinal , Redes e Vias Metabólicas , Administração Oral , Animais , Antidepressivos/metabolismo , Antidepressivos/farmacocinética , Antidepressivos/farmacologia , Ácido Benzoico/metabolismo , Biotransformação , Hidrocarbonetos Aromáticos com Pontes/metabolismo , Hidrocarbonetos Aromáticos com Pontes/farmacocinética , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Carboxilesterase/metabolismo , D-Aminoácido Oxidase/antagonistas & inibidores , Ratos Sprague-Dawley
17.
J Nat Prod ; 80(12): 3314-3318, 2017 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-29227099

RESUMO

Broadleaf weeds are very costly for crop growers. Additional herbicidal compounds need to be obtained, especially from natural sources. Extracts of Icacina trichantha were evaluated for responses in germinating seeds and seedlings of rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana). An ethyl acetate fraction of I. trichantha tuber and a diterpenoid constituent, icacinol (1), were found to have impacts on germination and growth of seedlings. The seed germination inhibitory activity on rice was minimal, but significant on Arabidopsis. While rice indicated some growth delay in leaf expansion in the presence of 1, the effects appeared temporary; chlorophyll and anthocyanins were not significantly altered compared to DMSO controls. Rice seedlings attained biomass similar to DMSO controls, and rice grains per panicle were not significantly different from the DMSO controls. On the other hand, Arabidopsis exhibited damage to leaf expansion, reduced chlorophyll, and increased anthocyanins in aerial portions of the seedlings. Icacinol (1) may be a suitable chemical agent to investigate further for the treatment of eudicot weeds.


Assuntos
Arabidopsis/efeitos dos fármacos , Diterpenos/farmacologia , Herbicidas/farmacologia , Oryza/efeitos dos fármacos , Plântula/efeitos dos fármacos , Sementes/efeitos dos fármacos , Germinação/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Plantas Daninhas/efeitos dos fármacos
18.
Acta Pharm Sin B ; 7(4): 485-490, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28752034

RESUMO

Sixteen compounds, including two new natural products (1 and 2), were obtained from the twigs of Illicium angustisepalum. The structures were elucidated based on NMR, MS, IR data and optical rotation values. Compounds 4, 5, 6 and 8 displayed moderate antibacterial activities against clinical isolates; compounds 4, 5, 8, 9 and 15 protected neural cells against oxidative stress; and compounds 10 and 14 exhibited anti-acetylcholinesterase activity.

20.
Phytomedicine ; 23(12): 1475-1483, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27765368

RESUMO

BACKGROUND: Hepatic steatosis (HS) is the early stage of nonalcoholic fatty liver disease which is caused by impaired hepatic lipid homeostasis. Cyclocarya paliurus, an herbal tea consumed in China, has been demonstrated to ameliorate abnormal lipid metabolism for the treatment of metabolic diseases. PURPOSE: We aimed to investigate the regulative effect of chloroform extract from Cyclocarya paliurus (ChE) on treatment of HS, as well as key factors involved in hepatic lipid metabolism. STUDY DESIGN: Sprague Dawley rats were fed with high-fat diet (HFD) for 6 weeks to induce HS and treated with or without ChE by gavage for 4 weeks. METHODS: The body weight, relative liver weight and liver fat content were measured. Serum and liver total cholesterol, triglyceride and non-esterified fatty acids, as well as hepatic malonaldehyde levels were accessed by biochemical methods. Serum and liver TNF-α levels were quantified by ELISA kit. Histologic analysis and 1H-MRS study were performed to evaluate HS level. RT-PCR and Western blot were also applied to observe the expression changes of key factors involved in hepatic lipid intake, synthesis, utilization and export. RESULTS: ChE significantly decreased the rats' body weight, serum lipid and TNF-α level. ChE also reduced their relative liver weight, liver fat content, hepatic oxidative products and TNF-α level. Hepatic steatosis in HFD-fed rats was effectively regressed after 2-weeks administration of ChE. Moreover, ChE treatment remarkably reduced HFD-induced high expression level of fatty acid synthesis genes (including sterol-regulatory element-binding protein 1, acetyl-CoA carboxylase 1 and fatty acid synthase). However, it had no effect on mRNA expression of some genes involved in lipid uptake, ß-oxidation and lipid outflow. CONCLUSION: ChE exerted a promising regression effect on HS due to a reduced level of serum non-esterified fatty acids which might lead to a decrease in the amount of lipid taken in by the liver, as well as owing to the inhibition of hepatic lipid de novo synthesis to reduce liver lipid production.


Assuntos
Dieta Hiperlipídica , Juglandaceae , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Acetil-CoA Carboxilase/metabolismo , Animais , China , Colesterol/sangue , Ácido Graxo Sintases/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Lipídeos/sangue , Fígado/metabolismo , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Ratos Sprague-Dawley , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/metabolismo
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