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1.
Medicine (Baltimore) ; 99(7): e19142, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049837

RESUMO

BACKGROUND: Depression is a kind of chronic and recurrent mental disorder, the main clinical characteristics of the patients are marked and persistent depression. At the same time, it is often accompanied by chronic physical disease, cognitive impairment, and functional damage, which is one of the common diseases that seriously threaten human health. At present, 3 kinds of oral Chinese patent medicine have clinical comparability in the treatment of depression of liver stagnation and spleen deficiency, but there is no evidence for clinical efficacy and safety. Therefore, this study aims to integrate the clinical related syndromes of direct and indirect comparison by using systematic evaluation and network meta-analysis (NMA). According to the data, the different Chinese patent medicines with the same evidence body for the treatment of the disease are collected, analyzed, and sequenced in a quantitative and comprehensive way, and then the advantages and disadvantages of the efficacy and safety between different Chinese patent medicines are screened out to get the best choice scheme, thus providing reference value and evidence-based theoretical evidence for the clinical optimization of drug selection. METHODS: Comprehensive retrieval of China National Knowledge Infrastructure, Chinese scientific journal database (VIP), China biological feature database (CBM) and WANFANG Data Chinese electronic database and the Cochrane Library, PubMed, Web of Science, and EMBASE foreign database. Search and publish the clinical randomized controlled trials of these 3 Chinese patent medicines combined with fluoxetine compared with fluoxetine. The retrieval time is from the establishment of the database to October 31, 2019. The 2 first authors will screen the literatures that meet the inclusion criteria, extract the data independently according to the predesigned rules, and evaluate the literature quality and bias risk of the included research according to the Cochrane 5.1 manual standard. R and Aggregate Data Drug Information System software were used for data consolidation and NMA to evaluate the ranking probability of all interventions. RESULTS: This result will show that the best oral Chinese patent medicine to assist the treatment of liver stagnation and spleen deficiency depression provides reliable evidence. CONCLUSION: This study will provide systematic evidence-based medicine evidence for TCM assisted treatment of depression of liver stagnation and spleen deficiency type, and help clinicians, patients with depression and decision-makers to make more effective, safer, and economic optimal treatment plan in the decision-making process. PROSPERO REGISTRATION NUMBER: CRD42019115695.


Assuntos
Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatopatias/tratamento farmacológico , Medicina Tradicional Chinesa , Esplenopatias/tratamento farmacológico , Depressão/complicações , Humanos , Hepatopatias/etiologia , Esplenopatias/etiologia , Revisão Sistemática como Assunto
2.
J Agric Food Chem ; 68(8): 2393-2405, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31995979

RESUMO

Hyperglycemia-induced oxidative stress can cause liver damage in diabetes, and protein hydrolysates with antidiabetic and antioxidant properties are emerging as a potential therapy. In this study, protective effects of casein hydrolysates against live oxidative damage in streptozotocin/high-fat-induced diabetic rats were studied and potentially bioactive peptides were explored by an integrated approach of differential peptide and in silico analysis. Results showed that different casein hydrolysates significantly alleviated liver oxidative damage (p < 0.05) via different mechanisms. Particularly, casein hydrolyzed by a papain-flavourzyme combination (P-FCH) treatment significantly improved liver antioxidant enzyme activities by enhancing nuclear factor erythroid 2-related factor 2 (Nrf2) transcription (p < 0.05). Furthermore, 18 peptides were screened as potential bioactive peptides by analyzing differential peptides among different hydrolysates combined with in silico prediction. Among them, the dipeptide WM might directly inhibit the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 interaction as potential Nrf2 activators. These results suggested that P-FCH might be an alternative way to treat liver damage in diabetes.


Assuntos
Caseínas/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/administração & dosagem , Animais , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Hepatopatias/genética , Hepatopatias/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Peptídeos/química , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
3.
Expert Opin Investig Drugs ; 29(2): 179-190, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31948298

RESUMO

Introduction: Globally, deaths from liver disease are increasing and for most patients there are few curative options. Fibrosis or scarring is often associated with the formation and progression of liver disease; however, clinical anti-fibrotic therapies are lacking. Recent work has shown that Wnt signaling, a signaling pathway that is necessary for embryonic development and cancer, can also regulate scar formation in the liver.Areas covered: This article seeks to shed light on the dualistic role of Wnt signaling in liver regeneration following injury and how Wnt signaling can regulate scar formation. It also discusses how Wnt signaling cooperates with other classical fibrogenic signaling cascades, such as TGFß signaling. Finally, the article examines recent advances in the development of Wnt signaling pathway inhibitors and asks whether repurposing these agents as anti-fibrotic therapies is a realistic option.Expert opinion: The understanding of Wnt signaling in liver regeneration and fibrosis is in its infancy and whilst new generations of Wnt pathway inhibitors have shown anti-fibrotic effects, further research is necessary to enhance our understanding of the Wnt-landscape in different patterns of liver disease. This will accelerate the development of more specific Wnt inhibitor-based anti-fibrotics.


Assuntos
Cirrose Hepática/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Cicatriz/prevenção & controle , Progressão da Doença , Desenvolvimento de Medicamentos , Humanos , Cirrose Hepática/fisiopatologia , Hepatopatias/fisiopatologia , Regeneração Hepática/efeitos dos fármacos
4.
Adv Exp Med Biol ; 1182: 217-242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777021

RESUMO

Ganoderma lucidum (G. lucidum, Lingzhi) has a wide range of hepatoprotective effects. Its bioactive substances include triterpenoids, polysaccharides, sterols, steroids, peptides, and other bioactive ingredients. Based on our research and other references, this chapter discusses the hepatoprotective effects of G. lucidum in different liver diseases, including hepatocellular carcinoma, nonalcoholic liver disease, alcoholic liver disease, hepatitis B, inflammation, fibrosis, and toxicant-induced liver injury. The liver protective mechanisms of G. lucidum vary from diseases to diseases. This chapter will summarize the hepatoprotective effects of G. lucidum on different liver injury and their clinical applications.


Assuntos
Produtos Biológicos/farmacologia , Hepatopatias/tratamento farmacológico , Fígado/efeitos dos fármacos , Reishi/química , Humanos
5.
J Agric Food Chem ; 67(47): 13082-13092, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31671940

RESUMO

Elevated circulating level of the intestinal microbiota-derived l-carnitine metabolite trimethylamine-N-oxide (TMAO) has recently been linked to many chronic diseases. The purpose of our study was to investigate the effects of omega-7-enriched Decaisnea insignis seed oil (DISO) on reducing TMAO formation to prevent the l-carnitine-induced hepatic damage in mice. Feeding of mice with 3% l-carnitine in drinking water clearly increased the serum and urinary levels of TMAO (p < 0.05 vs Normal), whereas the serum and urinary TMAO formation was sharply reduced by DISO administration (p < 0.05). Meanwhile, DISO resulted in strong inhibition against the elevation of hepatic injury marker (AST, ALT, and ALP) activities and dyslipidemia (TC, TG, LDL-C, and HDL-C), as well as liver inflammatory cytokine (IL-1, IL-6, TNF-α, and TNF-ß) release in l-carnitine-fed mice (p < 0.05). As revealed by 16S rDNA gene sequencing, DISO significantly inhibited the l-carnitine-induced elevations in the abundance of Firmicutes, Proteobacteria, and Erysipelotrichaceae and the increases in the proportion of Lactobacillus and Akkermansia, revealing that DISO attenuated the l-carnitine-caused gut dysbiosis. These findings suggested that DISO could alleviate liver dysfunction in l-carnitine-fed mice, which might be due to the protection against TMAO formation by modulating the gut microbiota.


Assuntos
Carnitina/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatias/tratamento farmacológico , Magnoliopsida/química , Óleos Vegetais/farmacologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Humanos , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias/metabolismo , Hepatopatias/microbiologia , Masculino , Metilaminas/efeitos adversos , Camundongos , Sementes/química
6.
Molecules ; 24(20)2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615114

RESUMO

Silymarin, the extract of milk thistle, and its major active flavonolignan silybin, are common products widely used in the phytotherapy of liver diseases. They also have promising effects in protecting the pancreas, kidney, myocardium, and the central nervous system. However, inconsistent results are noted in the different clinical studies due to the low bioavailability of silymarin. Extensive studies were conducted to explore the metabolism and transport of silymarin/silybin as well as the impact of its consumption on the pharmacokinetics of other clinical drugs. Here, we aimed to summarize and highlight the current knowledge of the metabolism and transport of silymarin. It was concluded that the major efflux transporters of silybin are multidrug resistance-associated protein (MRP2) and breast cancer resistance protein (BCRP) based on results from the transporter-overexpressing cell lines and MRP2-deficient (TR-) rats. Nevertheless, compounds that inhibit the efflux transporters MRP2 and BCRP can enhance the absorption and activity of silybin. Although silymarin does inhibit certain drug-metabolizing enzymes and drug transporters, such effects are unlikely to manifest in clinical settings. Overall, silymarin is a safe and well-tolerated phytomedicine.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Hepatopatias/tratamento farmacológico , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas de Neoplasias/genética , Silimarina/uso terapêutico , Animais , Antioxidantes , Flavonolignanos/metabolismo , Humanos , Hepatopatias/genética , Hepatopatias/patologia , Cardo Mariano/química , Fitoterapia , Ratos , Silibina/metabolismo
7.
Expert Opin Investig Drugs ; 28(10): 891-902, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31550938

RESUMO

Introduction: Alpha-1 antitrypsin deficiency (AATD) is most often associated with chronic lung disease, early onset emphysema, and liver disease. The standard of care in lung disease due to AATD is alpha-1 antitrypsin augmentation but there are several new and emerging treatment options under investigation for both lung and liver manifestations. Areas covered: We review therapeutic approaches to lung and liver disease in alpha-1 antitrypsin deficiency (AATD) and the agents in clinical development according to their mode of action. The focus is on products in clinical trials, but data from pre-clinical studies are described where relevant, particularly where progression to trials appears likely. Expert opinion: Clinical trials directed at lung and liver disease separately are now taking place. Multimodality treatment may be the future, but this could be limited by treatment costs. The next 5-10 years may reveal new guidance on when to use therapeutics for slowing disease progression with personalized treatment regimes coming to the forefront.


Assuntos
Desenvolvimento de Medicamentos/métodos , Drogas em Investigação/administração & dosagem , Deficiência de alfa 1-Antitripsina/tratamento farmacológico , Animais , Progressão da Doença , Drogas em Investigação/farmacologia , Humanos , Hepatopatias/tratamento farmacológico , Hepatopatias/etiologia , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologia , Medicina de Precisão/métodos , Deficiência de alfa 1-Antitripsina/fisiopatologia
8.
J Agric Food Chem ; 67(42): 11627-11637, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31553177

RESUMO

Liver diseases alter the gut microbiota, but several lactic acid bacteria can reduce the degree of liver damage. The present study investigated whether Lactobacillus buchneri TCP016 reduces the degree of liver damage by modifying the gut microbiota via its exopolysaccharides (EPSs). First, it was illustrated that the main EPS (EPS016; molecular weight = 8.509 × 104 Da) comprised rhamnose, xylose, glucosamine, glucuronic acid, galactose, galacturonic acid, glucose, and mannose in molar ratios of 9.2:3.9:3.8:2.8:2.1:2.0:1.6:1.0. Our data showed that EPS016 alleviated the increase in plasma and hepatic enzyme and cytokine levels, increased superoxide dismutase and glutathione activity, and alleviated bacterial translocation to the liver and mesenteric lymph nodes in vivo. Furthermore, EPS016 ameliorated intestinal mucosal injury and gut flora dysbiosis, thereby decreasing the enrichment of Helicobacteraceae, Lachnospiraceae, and Enterobacteriaceae and increasing the abundance of Lactobacillus, Rikenellaceae, Bacteroidaceae, Bacteroidales_S24-7_group, and Prevotellaceae. These findings indicated that EPS016 inhibits lipopolysaccharides/d-galactosamine-induced liver injury and improves the modification of the gut microbiota.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus/química , Hepatopatias/tratamento farmacológico , Polissacarídeos Bacterianos/administração & dosagem , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Feminino , Galactosamina/efeitos adversos , Humanos , Lactobacillus/metabolismo , Lipopolissacarídeos/efeitos adversos , Hepatopatias/etiologia , Hepatopatias/microbiologia , Camundongos Endogâmicos BALB C , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/metabolismo
9.
Bratisl Lek Listy ; 120(8): 558-562, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379176

RESUMO

Genistein is a natural compound from the class of isoflavonoids found in high concentrations in legumes and soybeans. In this experimental study; we suggest that genistein might cause favorable outcomes in the hepatic surgery because of its protective effects on hepatic ischemia‒reperfusion injury (Tab. 2, Fig. 6, Ref. 28). Keywords: genistein, isoflavonoids,legumes, soybeans, hepatic surgery, ischemia‒reperfusion injury.


Assuntos
Genisteína/farmacologia , Hepatopatias/tratamento farmacológico , Fígado/cirurgia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Fígado/fisiopatologia , Ratos , Soja/química
10.
AAPS PharmSciTech ; 20(7): 293, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31432294

RESUMO

In this study, a novel human serum albumin nanoparticle loading silybin-phospholipid complex (SLNPs) was developed for liver targeting after intravenous administration. The preparation of the drug delivery system consisted of two steps; initially, a silybin-phospholipid complex (SLC) was produced to improve the lipophilicity of SLB to then achieve enhanced encapsulation of SLB in albumin nanoparticles. FT-IR and XRD analysis confirmed the successful formation of SLC. The complex ratio of SLC in the first step was 99.6%. The encapsulation efficiency and drug loading of SLNPs in the second step were 96.2% and 5.6%, respectively. SLNPs were spherical and well-dispersed, with a zeta potential of approximately - 10 mV, and a mean particle size around 200 nm. An in vivo tissue distribution experiment and a pharmacodynamic experiment showed that, compared with SLB solution, SLNPs had an improved SLB accumulation in the liver. The hepatoprotective effect of SLNPs on CCl4-induced acute liver damage was evaluated. CCl4-damaged mice showed an increased enzymatic activity of ALT and AST; however, enzyme levels returned to near-normal levels in high-dose SLNP-treated mice. As SLNPs combine the enhanced oil solubility of SLC and the passive targeting of albumin nanoparticles, they possess great potential for the treatment of acute liver damage.


Assuntos
Albuminas/química , Hepatopatias/tratamento farmacológico , Fosfolipídeos/química , Silibina/química , Administração Intravenosa , Animais , Sistemas de Liberação de Medicamentos , Humanos , Camundongos , Nanopartículas/administração & dosagem , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Distribuição Tecidual
11.
Exp Hematol ; 77: 51-60.e1, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31404577

RESUMO

Sickle cell disease (SCD) is a recessively inherited blood disorder caused by abnormal ß-globin production. The ß-globin mutation changes erythrocyte morphology into a sickle shape and increases erythrocyte vulnerability to hemolysis. Oxidative stress and concomitant inflammation eventually result in damage to multiple organs. Nrf2 is a master regulator of the oxidative stress response, homeostasis, and metabolism. Keap1 modulates Nrf2 protein levels; Nrf2 inducers alter nuclear Nrf2 levels by interacting with Keap1. Genetic modification of Keap1 helps to reduce inflammation and tissue damage in SCD model mice through Nrf2 induction. Here, we investigated the benefits of a mild and safe Nrf2 agonist, sulforaphane (SFN), in ameliorating SCD pathology in a murine model. SFN is a phytochemical and is found in cruciferous vegetables as its inert precursor, glucoraphanin. We found that dietary SFN administration for 14 days or 2 months increased the expression of Nrf2-dependent cytoprotective genes, but SFN uptake did not have deleterious effects on the food consumption and growth of SCD model mice. SFN ameliorated the liver damage of SCD mice, which could be validated by the rescue of liver function and the significantly reduced liver necrotic area. SFN administration also helped to eliminate heme released from lysed sickle cells. These results indicate that dietary supplementation with SFN relieves SCD symptoms by inducing Nrf2 and support our contention that SFN is a potential drug for the long-term treatment of children with SCD.


Assuntos
Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/metabolismo , Suplementos Nutricionais , Isotiocianatos/farmacologia , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Fígado/metabolismo , Anemia Falciforme/genética , Anemia Falciforme/patologia , Animais , Modelos Animais de Doenças , Feminino , Heme/genética , Heme/metabolismo , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fígado/patologia , Hepatopatias/genética , Hepatopatias/patologia , Masculino , Camundongos , Camundongos Transgênicos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo
12.
Niger J Physiol Sci ; 34(1): 33-42, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31449269

RESUMO

Diabetes Mellitus (DM) is a leading pan-systemic endocrine disorder with attendant high morbidity and mortality owing to its deleterious effects on vital body organs caused by untreated chronic hyperglycemia, attendant oxidative stress and glycation processes. The present study is designed to investigate possible protective role and mechanism(s) of action 125-500 mg/kg/day of Morinda lucida aqueous stem bark extract (MLASE) on renal and hepatic functions in alloxan-induced hyperglycemic rats for 8 days. Forty-two alloxan-induced hyperglycemiic male Wistar rats were randomly allotted to Groups II-VI and orally treated with 10 ml/kg/day distilled water, 5 mg/kg/day glibenclamide, 125 mg/kg MLASE, 250 mg/kg MLASE, and 500 mg/kg/day MLASE, respectively. Group I normal rats served as untreated control and were orally treated with 10 ml/kg of distilled water, all under same sham-handling. Blood samples were taken for measurement of fasting blood glucose, renal and hepatic function profile. Liver and kidney tissue samples were taken for determination of the activities of oxidative stress markers such as malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GPx), catalase (CAT) and superoxidase dismutase (SOD). Results showed that intraperitoneal injection with 120 mg/kg of alloxan in cold 0.9% normal saline reliably and significantly induced a steadily sustained hyperglycemia which were ameliorated by short-term oral treatment with 125-500 mg/kg/day of MLASE, dose dependently, similar to that ameliorated by the standard antihyperglycemic drug, glibenclamide. Similarly, MLASE significantly mitigated against derangements in the measured renal and hepatic function parameters as well as oxidative stress induced by alloxan-induced hyperglycemia. In conclusion, results of this study showed the protective role of 125-500 mg/kg/day of MLASE in chronic hyperglycemia-associated renal and hepatic dysfunctions which was mediated via antioxidant and free radical scavenging activities of MLASE.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Depuradores de Radicais Livres/uso terapêutico , Nefropatias/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Morinda , Extratos Vegetais/uso terapêutico , Animais , Diabetes Mellitus Experimental/metabolismo , Relação Dose-Resposta a Droga , Depuradores de Radicais Livres/isolamento & purificação , Nefropatias/metabolismo , Hepatopatias/metabolismo , Masculino , Casca de Planta , Extratos Vegetais/isolamento & purificação , Caules de Planta , Ratos , Ratos Wistar , Água
13.
Int J Immunopathol Pharmacol ; 33: 2058738419862736, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31298048

RESUMO

Hepatic ischemia/reperfusion injury (IRI) is a clinical condition that may lead to cellular injury and organ dysfunction that can be observed in different conditions, such as trauma, shock, liver resection, and transplantation. Moderate levels of nitric oxide (NO) produced by the endothelial isoform of the NO synthase protect against liver IRI. GIT-27NO is a NO-derivative of the toll-like receptor 4 antagonist VGX-1027 that has been shown to possess both antineoplastic and immunomodulatory properties in vitro and in vivo. In this study, we have investigated the effects of this compound in vitro, in a model of oxidative stress induced in HepG2 cells by hydrogen peroxide (H2O2), and in vivo, in a rat model of IRI of the liver. GIT-27NO significantly counteracted the toxic effects induced by the H2O2 on the HepG2 cells and in vivo, GIT-27NO reduced the transaminase levels and the histological liver injury by reducing necrotic areas with preservation of viable tissue. These effects were almost similar to that of the positive control drug dimethyl fumarate. These data suggest that the beneficial effect of GIT-27NO in the hepatic IRI can be secondary to anti-oxidative effects and hepatocyte necrosis reduction probably mediated by NO release.


Assuntos
Hepatopatias/tratamento farmacológico , Fígado/efeitos dos fármacos , Óxido Nítrico/metabolismo , Oxidiazóis/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fumarato de Dimetilo/farmacologia , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , Fígado/metabolismo , Hepatopatias/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo
14.
J Med Food ; 22(8): 833-840, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31268397

RESUMO

Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV) and considered as a potential metabolic regulator. The purpose of this study was to compare the effects of PIC and RSV on parameters affecting inflammation, oxidative stress, and sirtuins (Sirt). Male C57BL/6J mice, 20 weeks old, were assigned to the following groups; (1) lean control, (2) high-fat diet control (HF), (3) HF_PIC, and (4) HF_RSV. Oral administration of PIC and RSV (10 mg/kg/day) for 4 weeks improved glucose control as shown by decreasing levels of area under the curve (AUC) during the oral glucose tolerance test compared with HF group. PIC improved glycemic control by increasing hepatic levels of insulin receptor and AMP-activated protein kinase. PIC increased the levels of Sirt1, Sirt3, and Sirt6 and also increased two downstream targets of Sirt, peroxisome proliferator-activated receptor gamma coactivator 1-alpha and forkhead box O1, in the liver. The inflammatory markers, interleukin (IL)-1 and IL-6, in the liver were downregulated by RSV treatment. Exposure to PIC and RSV significantly lowered hepatic levels of tumor necrosis factor-alpha. However, PIC and RSV treatments showed minimal effects on hepatic markers of oxidative stress. The levels of antioxidant enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), were only increased in livers of RSV-treated mice compared with HF control mice. In conclusion, PIC was superior to an equal concentration of RSV in the regulation of Sirt and its downstream targets as well as insulin signaling-related parameters, while RSV potentially suppressed levels of proinflammatory markers and increased NQO1 protein levels.


Assuntos
Hepatopatias/tratamento farmacológico , Fígado/imunologia , Resveratrol/administração & dosagem , Sirtuínas/genética , Estilbenos/administração & dosagem , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Fígado/efeitos dos fármacos , Hepatopatias/etiologia , Hepatopatias/genética , Hepatopatias/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/imunologia , Estresse Oxidativo/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/imunologia , Sirtuínas/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
15.
J Vet Med Sci ; 81(8): 1162-1172, 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31270307

RESUMO

The metabolism of aflatoxin B1 (AFB1) generates reactive oxygen species (ROS) that destroys hepatocytes. Meanwhile, astaxanthin (AX) is known to have stronger antioxidative activity than other carotenoids. This study aimed to investigate hepatoprotective role of AX from AFB1-induced toxicity in rat by histopathological study and immunohistochemistry of Cu/Zn-SOD (SOD1) which acts as the first enzyme in antioxidative reaction against cell injury from ROS. Twenty Wistar rats were randomly divided into 4 groups. The control and AFB1 groups were gavaged by water for 7 days followed by a single DMSO and 1 mg/kg AFB1, respectively. The AXL+ AFB1 and AXH+ AFB1 groups were given of 5 mg/kg and 100 mg/kg AX for 7 days before 1 mg/kg AFB1 administration. The result showed significantly elevated liver weight per 100 g body weight in AFB1 group. The histopathological finding revealed vacuolar degeneration, necrosis, megalocytosis and binucleation of hepatocytes with bile duct hyperplasia in AFB1 group. The severities of pathological changes were sequentially reduced in AXL+AFB1 and AXH+AFB1 groups. Most rats in AXH+AFB1 group owned hypertrophic hepatocytes and atypical proliferation of cholangiocytes which are adaptive responses to severe hepatocyte damage. The SOD1 expression was also significantly higher in AXH+AFB1 group than solely treated AFB1 and AXL+AFB1 groups. In conclusion, AX alleviated AFB1-induced liver damage in rat by stimulating SOD1 expression and transdifferentiation of cholangiocytes in dose dependent manner.


Assuntos
Aflatoxina B1/toxicidade , Antioxidantes/farmacologia , Fígado/efeitos dos fármacos , Venenos/toxicidade , Superóxido Dismutase/metabolismo , Animais , Antioxidantes/uso terapêutico , Interações de Medicamentos , Fígado/enzimologia , Fígado/patologia , Hepatopatias/tratamento farmacológico , Hepatopatias/patologia , Micotoxicose/tratamento farmacológico , Micotoxicose/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Xantofilas/farmacologia , Xantofilas/uso terapêutico
16.
Int J Mol Sci ; 20(14)2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31323789

RESUMO

The ginseng berry contains a variety of biologically active compounds and has a higher ginsenoside content than its roots. This study focused on the hepatoprotective activity of ginseng berry extract prepared by enzyme treatment (EGB) compared to the non-enzyme-treated ginseng berry extract (GB) and quality control of EGB. The feeding effect of EGB on alcohol-induced liver damage (AILD) was investigated by measuring the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with those of EtOH-fed mice. Furthermore, cytokine levels in the culture supernatants of EGB- or GB-treated RAW 264.7 cells were determined by enzyme-linked immunosorbent assay. The developed method was applied to the simultaneous quantification of four major ginsenosides in EGB using UPLC-QTOF/MS. Treatment with EGB at a dose of 0.5 or 1 mg/mouse significantly suppressed the AST and ALT levels in mice with AILD. Enzyme-treated ginseng berry was also found to suppress the production of inflammatory mediators like nitric oxide (NO), tumor-necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, showing higher activity than that of GB. The amount of ginsenoside Re, F5, F3, and Rd in the EGB obtained using UPLC-QTOF/MS was 45.9, 3.3, 4.0, and 6.2 mg/g, respectively. These results suggest that EGB has a potential effect on AILD, and its hepatoprotective effect provides beneficial insights into developing new candidates for the prevention and cure of AILD. Also, this study demonstrated the utility of UPLC-QTOF/MS-based major compounds for quality control (QC) of EGB.


Assuntos
Anti-Inflamatórios/uso terapêutico , Frutas/química , Fígado/efeitos dos fármacos , Panax/química , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Sobrevivência Celular/efeitos dos fármacos , Dinoprostona/sangue , Ginsenosídeos/química , Ginsenosídeos/uso terapêutico , Interleucina-6/sangue , Lipopolissacarídeos/toxicidade , Fígado/lesões , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Células RAW 264.7 , Fator de Necrose Tumoral alfa
17.
Food Funct ; 10(8): 4861-4867, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31334539

RESUMO

This study investigates the acute anti-inflammatory activity of Mangifera indica L. leaf extract and mangiferin in the liver of rats fed a cafeteria diet. This study was a randomized longitudinal experimental study. The animals were divided into three groups - Control: cafeteria diet (CD); Extract: CD + leaf extract (250 mg kg-1); and Mangiferin: CD + mangiferin (40 mg kg-1). Body weight and food intake were measured every week. On day eight, mRNA and protein expression of inflammatory markers were evaluated in the liver. Also, liver weight, SOD activity and malondialdehyde concentration were measured. Treatment for only eight days with mango leaf extract and mangiferin increased SOD activity. Mangiferin intake increased the mRNA expression of PPAR-α and HSP72. The leaf extract treatment enhanced PPAR-α mRNA expression. Mangiferin and leaf extract consumption caused a lower concentration of NFκB (p65) in nuclear extracts, and greater IL-10 mRNA and protein levels. This study highlights the potential of acute treatment with mango leaf extract and mangiferin to prevent liver inflammation caused by fat-rich diets. These results indicate a new use for a product that has low cost, is found in great amounts, and is not routinely used.


Assuntos
Anti-Inflamatórios/administração & dosagem , Hepatopatias/tratamento farmacológico , Mangifera/química , Extratos Vegetais/administração & dosagem , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatias/etiologia , Hepatopatias/genética , Hepatopatias/imunologia , Masculino , Malondialdeído/imunologia , PPAR alfa/genética , PPAR alfa/imunologia , Fitoterapia , Folhas de Planta/química , Ratos
18.
J Therm Biol ; 83: 8-21, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31331528

RESUMO

Heat stress (HS) is a major international problem which has attracted a considerable attention due to its oxidative tissue effects and high morbidity and mortality rates, especially among elderly people. Discovering an effective antioxidant is pivotal for overcoming HS-induced injury. Therefore, the aim of this study was to estimate the hepatic protective effects of orally supplemented resveratrol (RES) against HS-mediated liver injury in young and old male Wistar albino rats. Compared to control rats, RES administered orally at a dose of 20 mg/kg BW for 21 successive days efficiently ameliorated HS-induced oxidative damage by significantly increasing (P ≤ 0.05) the level of reduced glutathione and glutathione peroxidase, and decreasing the levels of malondialdehyde and TNF-α in hepatic tissue of both young and aged rats. However, level of NF-κB was downregulated significantly in aged rats rather than young rats. Moreover, RES significantly decreased (P ≤ 0.05) the serum levels of aspartate transaminase and alkaline phosphatase in both ages of rats compared to their corresponding HS-stressed rats. Furthermore, RES upregulated the immunohistochemical expression of caspase 3 and heat shock protein 70 in young and aged rats, however it was more pronounced in young one. In addition, RES administration moderately normalized (P ≤ 0.0001) the harmful effects of HS on the hepatic architecture of both young and aged rats. In conclusion, this study reveals for the first time that RES exerts promising hepato-ameliorative effects against HS-induced oxidative stress in the young and aged rats via its antioxidant, anti-inflammatory, and anti-apoptotic effect, as well as via its inhibitory effect against the NF-κB signalling in a cellular system.


Assuntos
Antioxidantes/uso terapêutico , Proteínas de Choque Térmico HSP70/metabolismo , Transtornos de Estresse por Calor/complicações , Hepatopatias/tratamento farmacológico , NF-kappa B/metabolismo , Resveratrol/uso terapêutico , Fosfatase Alcalina/sangue , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Apoptose , Aspartato Aminotransferases/sangue , Fígado/efeitos dos fármacos , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Hepatopatias/etiologia , Hepatopatias/metabolismo , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Resveratrol/administração & dosagem , Resveratrol/farmacologia , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
19.
Biomed Pharmacother ; 117: 109128, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31234023

RESUMO

Liver diseases are clinically common and present a substantial public health issue. Many of the currently available drugs for the treatment of liver diseases suffer from limitations that include low hepatic distribution, lack of target effects, poor in vivo stability and adverse effects on other organs. Consequently, conventional treatment of hepatic diseases is ineffective. TCM is commonly used in the treatment of liver diseases worldwide, particularly in China, and has advantages over conventional therapy. HTDDS can be designed to enhance clinical efficacy in the treatment of liver diseases. We have conducted an extensive review of 335 studies reported since 1964. These included about 166 references involving the treatment of liver diseases with TCM (covering active components of TCM, single TCM and Chinese medicine formulas), 169 reports on HTDDS and background studies on liver-related diseases. Here we review the long history of TCM in the treatment of liver diseases.We have also reviewed the status of studies on active components of TCM using nanotechnology-based targeted delivery systems to provide support for further research and development of TCM-based targeted preparations for the treatment of liver disease.


Assuntos
Sistemas de Liberação de Medicamentos , Hepatopatias/tratamento farmacológico , Fígado/patologia , Medicina Tradicional Chinesa , Animais , Portadores de Fármacos/química , Humanos , Nanopartículas/química
20.
Handb Exp Pharmacol ; 256: 237-264, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236688

RESUMO

Bile acids (BAs) are key molecules in generating bile flow, which is an essential function of the liver. In the last decades, there have been great advances in the understanding of BA physiology, and new insights have emerged regarding the role of BAs in determining cell damage and death in several liver diseases. This new knowledge has helped to better delineate the pathophysiology of cholestasis and the adaptive responses of hepatocytes to cholestatic liver injury as well as of the mechanisms of injury of biliary epithelia. In this context, therapeutic approaches for liver diseases using hydrophilic BA (i.e., ursodeoxycholic acid, tauroursodeoxycholic, and, more recently, norursodeoxycholic acid), have been revamped. In the present review, we summarize current experimental and clinical data regarding these BAs and its role in the treatment of certain liver diseases.


Assuntos
Hepatopatias/tratamento farmacológico , Ácido Tauroquenodesoxicólico/farmacologia , Ácido Ursodesoxicólico/análogos & derivados , Ácido Ursodesoxicólico/farmacologia , Ácidos e Sais Biliares , Colestase , Humanos , Fígado
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