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1.
Chem Biol Interact ; 311: 108794, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31421115

RESUMO

Acanthoic acid (AA) is a pimaradiene diterpene isolated from Acanthopanax koreanum Nakai (Araliaceae), with anti-inflammatory and hepatic-protective effects. The present study intended to reveal the effect and mechanism of AA on nonalcoholic fatty liver disease (NAFLD) associated with lipid accumulation by activating Farnesoid X receptor (FXR) and liver X receptors (LXRs) signaling. C57BL/6 mice were received a modified Lieber-DeCarli diet with 71% high-fat (L-D) and treated with AA (20 and 40 mg/kg) or equal volume of saline for 12 weeks. The regulation of AA on lipid accumulation was also detected in pro-steatotic stimulated AML12 cells with palmitic acid (PA). When L-D diet-fed mice were treated with AA, loss in body weight, liver index, and liver lipid droplet were observed along with reduced triglyceride (TG) and serum transaminase. Furthermore, AA decreased sterol regulatory element binding protein 1 (SREBP-1) and target genes expression, regulated PPARα and PPARγ expressions, ameliorated hepatic fibrosis markers, enhanced hepatic FXR and LXR, and regulated AMPK-LKB1 and SIRT1 signaling pathway. Moreover, AA attenuated lipid accumulation via FXR and LXR activation in steatotic AML-12 cells, which was confirmed by guggulsterones (FXR antagonist) or GW3965 (LXR agonist). Activation of FXR and LXR signaling caused by AA might increase AMPK-SIRT1 signaling and then contribute to modulating lipid accumulation and fatty acid synthesis, which suggested that activated FXR-LXR axis by AA represented an effective strategy for relieving NAFLD.


Assuntos
Diterpenos/farmacologia , Lipogênese/efeitos dos fármacos , Receptores X do Fígado/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Peso Corporal/efeitos dos fármacos , Linhagem Celular , Dieta Hiperlipídica , Diterpenos/química , Regulação da Expressão Gênica/efeitos dos fármacos , Receptores X do Fígado/agonistas , Receptores X do Fígado/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , PPAR alfa/genética , PPAR alfa/metabolismo , Ácido Palmítico/farmacologia , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/genética , Transdução de Sinais/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/sangue
2.
BMC Complement Altern Med ; 19(1): 156, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269941

RESUMO

BACKGROUND: The traditional Chinese medicine prescription, Qianggan formula have been confirmed to be effective on non-alcoholic steatohepatitis (NASH), however, the underlying molecular mechanisms remain obscure. METHODS: Thirty-six male C57BL/6 mice were randomly divided into three groups: normal chow diet group; methionine-and-choline-deficient diet (MCD) group, and Qianggan extract (QG) intervention group (0.4 g/kg daily) that fed with MCD. The efficacy of QG was biochemically and histologically evaluated. The expression profiles of messenger ribonucleic acids (mRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) were examined using microarray and verified by RT-qPCR. RESULTS: QG significantly improved the phenotypic characteristics of NASH, as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) levels and liver inflammatory cytokines were significantly decreased. By the cutoff of a 1.5-fold change and P < 0.05, 6193 mRNAs, 5692 lncRNAs and 4843 circRNAs were identified as differentially expressed between the MCD and normal groups, and 514 mRNAs, 1182 lncRNAs and 443 circRNAs were identified as differentially expressed between the QG and MCD groups. The intersections (244 mRNAs, 259 lncRNAs and 98 circRNAs) among the three groups were chosen for analysis. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed that most overlapping mRNAs were related to immune functions such as natural-killer-cell-mediated cytotoxicity, intestinal immune network for IgA production, and T cell receptor signaling pathway. Pathway interactions, protein-protein interactions and molecular complex detection (MCODE) analysis identified numerous immune-related hub genes e.g. natural cytotoxicity triggering receptor 1(Ncr1), C-X-C motif chemokine ligand 9 (Cxcl9), Klra1, and Cd28. Finally, two lncRNAs (Sngh1 and Slc36a3os) and four circRNAs (circ_0009029, circ_0004572, circ_0009212 and circ_0009453) in competing endogenous RNA (ceRNA) networks were constructed by Cytoscape, and immune-related mRNAs (e.g., Cd28, Cd8a, Il15, and Klrk1) were involved in the ceRNA networks. CONCLUSIONS: LncRNA and circRNA-associated immune ceRNA networks might be the targets of QG in alleviating NASH, and our work may provide valuable clues for exploring the mechanisms underlying the effect of QG.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fitoterapia , Animais , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Mapas de Interação de Proteínas , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Distribuição Aleatória
3.
J Agric Food Chem ; 67(27): 7726-7737, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31203627

RESUMO

Fructose as a daily sweetener is widely recognized as a risk catalyst for nonalcoholic fatty liver disease (NAFLD). The aim of current study is to evaluate the effects and molecular mechanism by which polyphenol-rich loquat fruit extract (LFP) prevents NAFLD in mice fed 30% fructose water (HF) for 8 weeks. Administration of LFP to HF-fed mice mitigated abnormal body weight, disordered lipid metabolism, oxidative stress, and inflammation through a mechanism regulated by the AKT, ChREBP/SREBP-1c, Nrf2, and TLR4/MyD88/TRIF pathways. LFP caused a significant decrease in the endotoxin content (16.67-12.7 EU/mL) in the liver of HF-fed mice. LFP not only improved HF-induced breakage of the intestinal barrier via interacting with tight junction proteins (ZO-1, occludin), mucin, and immunoreaction in the colon but also maintained normal colonic Firmicutes/Bacteroidetes ratios and the relative abundance of Veillonella in HF-fed mice. Our results suggest that LFP may serve as a nutritional agent for protecting liver in HF-fed mice.


Assuntos
Eriobotrya , Frutose/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Animais , Dieta , Frutose/administração & dosagem , Frutas/química , Glucose/metabolismo , Inflamação/prevenção & controle , Intestinos/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos
4.
Zhonghua Gan Zang Bing Za Zhi ; 27(5): 369-375, 2019 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-31177662

RESUMO

Objective: To investigate the relationship between gut microbiota structure and biochemical changes in patients with different types of nonalcoholic fatty liver disease (NAFLD), in order to provide evidence for clinical diagnosis and prevention of NAFLD. Methods: Forty-eight NAFLD cases (NAFLD group), 40 NAFLD cases with type 2 diabetes mellitus (NAFLD combined with type 2 diabetes mellitus group) and 30 healthy cases (healthy group) were randomly enrolled, and their body mass index, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein and uric acid were measured. Serum levels of TNF-alpha and fasting insulin were measured using ELISA, and then insulin resistance index was calculated. The gut microbiota of three groups of subjects was detected using 16S rDNA-based high-throughput sequencing. Lastly, the correlations between the various factors were analyzed. The comparison among groups was conducted by 2 test, and one-way ANOVA was used for comparison among groups with normal distribution and homogeneity of variance. Furthermore, the LSD method was used to compare the two groups. K-W rank sum test was used for comparison among groups without normal distribution or homogeneity of variance. Results: Body mass index, aspartate aminotransferase, triglyceride, total cholesterol, low density lipoprotein, uric acid, tumor necrosis factor-alpha, fasting insulin and insulin resistance index of NAFLD group were higher than healthy group, while the high-density lipoprotein was lower in the healthy group, and the difference was statistically significant (P< 0.05). Compared with NAFLD group, the life expectancy, fasting blood glucose and insulin resistance index of NAFLD combined with type 2 diabetes mellitus group were higher, while the body mass index, aspartic acid aminotransferase, total cholesterol and HDL levels were decreased, and the difference was statistically significant (P< 0.05). NAFLD group (P= 0.016) had decreased abundance of firmicutes than healthy group, and the abundancy of the firmicutes in the NAFLD combined with type 2 diabetes group was significantly lower (P< 0.001). The abundance of bacteroidetes in NAFLD combined with type 2 diabetes group was higher than healthy group, and the difference was statistically significant (P= 0.006). At the "genus level," the abundance of Roseburia and Subdoligranulum in the NAFLD group was decreased, while the Roseburia in the NAFLD group with type 2 diabetes group was significantly lower (P< 0.05). In addition, the abundance of Faecalibacterium, Blautia, Anaerostipes and Fusicatenibacter in NAFLD combined with type 2 diabetes group was lower than healthy group, and the difference was statistically significant (P< 0.001). Fusicatenibacter, Blautia, Anaerostipes, Faecalibacterium, and Roseburia were negatively correlated with fasting blood glucose and insulin resistance index levels (r< 0,P< 0.05), and positively correlated with high-density lipoprotein levels (r> 0,P< 0.05). Fusicatenibacter was negatively correlated with tumor necrosis factor-alpha (r= -0.211,P= 0.044), and Lachnoclostridium was positively correlated with body mass index, alanine aminotransferase, aspartate aminotransferase levels (r> 0,P< 0.05). Fusobacterium was positively correlated with aspartate aminotransferase level (r= 0.245,P= 0.019). Escherichia-shigella was positively correlated with fasting blood glucose, low-density lipoprotein, alanine aminotransferase, aspartate aminotransferase levels (r > 0,P< 0.05). Megamonas was negatively correlated with high-density lipoprotein levels (r= -0.231,P= 0.027). Conclusion: A structural change of gut microbiota had occurred in patients with NAFLD, suggesting changes in some of these bacterial genuses had relation to insulin resistance and inflammatory response, which may become a new target for the treatment of NAFLD.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Microbioma Gastrointestinal , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/metabolismo , Alanina Transaminase , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações
5.
Arq Gastroenterol ; 56(1): 28-33, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31141077

RESUMO

BACKGROUND: Insulin resistance, especially that induced by obesity, plays a central role in the development of non-alcoholic fatty liver disease. Although the evaluation of overweight patients is important, the nutritional assessment tools used in clinical practice have limitations. Neck circumference (NC), from this, becomes a viable and low-cost alternative, which seems to be related to the accumulation of fat in the hepatic tissue. OBJECTIVE: To evaluate the association between NC and metabolic alterations in patients with non- alcoholic fatty liver disease. METHODS: A cross-sectional study performed in 82 patients, of whom 76 underwent liver biopsy. We performed weight, height, abdominal circumference and NC measures. Values of NC ≥42 cm and ≥36 cm were considered as altered for men and women, respectively. Laboratory tests and liver biopsy result were collected in the participants' charts. We evaluated fasting blood glucose levels, insulin, glycosylated hemoglobin, triglycerides, total cholesterol, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), ferritin, alkaline phosphatase, gamma glutamyltransferase, albumin, total bilirubin, direct bilirubin, glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase and the HOMA-IR index. RESULTS: We evaluated eighty-two patients. Patients with altered NC had increased body mass index (P=0.043), abdominal circumference (P=0.007), insulin (P=0.003) and HOMA-IR (P=0.029) when compared to those with adequate NC. NC was significantly correlated with reduced levels of high-density cholesterol (HDL-C) in men (r= -042, P<0.05), increased insulin levels in men and female (rs=0.47; P<0.05 and rs=0.51; P<0.01, respectively), as well as higher HOMA-IR index both males (rs=0.49; P<0.01) and female (rs=0.30; P<0.05). There was no significant association between NC and liver outcomes (r=0.145; P=0.36). CONCLUSION: NC is associated with the HOMA-IR index in patients with non-alcoholic fatty liver disease. NC can be used in the screening of insulin resistance in these patients, considering that insulin resistance plays a key role in the progression of the disease.


Assuntos
Resistência à Insulina/fisiologia , Pescoço/anatomia & histologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Adulto , Biópsia , Glicemia/análise , Índice de Massa Corporal , HDL-Colesterol/sangue , Estudos Transversais , Feminino , Ferritinas/sangue , Homeostase/fisiologia , Humanos , Insulina/sangue , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Fatores Sexuais , Circunferência da Cintura
6.
Gastroenterology ; 157(3): 777-792.e14, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31078624

RESUMO

BACKGROUND & AIMS: We studied the role of interleukin 11 (IL11) signaling in the pathogenesis of nonalcoholic steatohepatitis (NASH) using hepatic stellate cells (HSCs), hepatocytes, and mouse models of NASH. METHODS: We stimulated mouse and human fibroblasts, HSCs, or hepatocytes with IL11 and other cytokines and analyzed them by imaging, immunoblot, and functional assays and enzyme-linked immunosorbent assays. Mice were given injections of IL11. Mice with disruption of the interleukin 11 receptor subunit alpha1 gene (Il11ra1-/-) mice and Il11ra1+/+ mice were fed a high-fat methionine- and choline-deficient diet (HFMCD) or a Western diet with liquid fructose (WDF) to induce steatohepatitis; control mice were fed normal chow. db/db mice were fed with methionine- and choline-deficient diet for 12 weeks and C57BL/6 NTac were fed with HFMCD for 10 weeks or WDF for 16 weeks. Some mice were given intraperitoneal injections of anti-IL11 (X203), anti-IL11RA (X209), or a control antibody at different timepoints on the diets. Livers and blood were collected; blood samples were analyzed by biochemistry and liver tissues were analyzed by histology, RNA sequencing, immunoblots, immunohistochemistry, hydroxyproline, and mass cytometry time of flight assays. RESULTS: HSCs incubated with cytokines produced IL11, resulting in activation (phosphorylation) of ERK and expression of markers of fibrosis. Livers of mice given injections of IL11 became damaged, with increased markers of fibrosis, hepatocyte cell death and inflammation. Following the HFMCD or WDF, livers from Il11ra1-/- mice had reduced steatosis, fibrosis, expression of markers of inflammation and steatohepatitis, compared to and Il11ra1+/+ mice on the same diets. Depending on the time of administration of anti-IL11 or anti-IL11RA antibodies to wild-type mice on the HFMCD or WDF, or to db/db mice on the methionine and choline-deficient diet, the antibodies prevented, stopped, or reversed development of fibrosis and steatosis. Blood samples from Il11ra1+/+ mice fed the WDF and given injections of anti-IL11 or anti-IL11RA, as well as from Il11ra1-/- mice fed WDF, had lower serum levels of lipids and glucose than mice not injected with antibody or with disruption of Il11ra1. CONCLUSIONS: Neutralizing antibodies that block IL11 signaling reduce fibrosis, steatosis, hepatocyte death, inflammation and hyperglycemia in mice with diet-induced steatohepatitis. These antibodies also improve the cardiometabolic profile of mice and might be developed for the treatment of NASH.


Assuntos
Anticorpos Neutralizantes/farmacologia , Hepatite/prevenção & controle , Subunidade alfa de Receptor de Interleucina-11/metabolismo , Interleucina-11/antagonistas & inibidores , Cirrose Hepática Experimental/prevenção & controle , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Animais , Morte Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Hepatite/genética , Hepatite/metabolismo , Hepatite/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-11/metabolismo , Subunidade alfa de Receptor de Interleucina-11/deficiência , Subunidade alfa de Receptor de Interleucina-11/genética , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/genética , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Transdução de Sinais/efeitos dos fármacos , Células THP-1
7.
Environ Pollut ; 251: 390-399, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31100570

RESUMO

Perchlorate is a pervasive, water-soluble contaminant that competitively inhibits the sodium/iodide symporter, reducing the available iodide for thyroid hormone synthesis. Insufficient iodide uptake can lead to hypothyroidism and metabolic syndromes. Because metabolism, obesity and non-alcoholic fatty liver disease (NAFLD) are tightly linked, we hypothesized that perchlorate would act as an obesogen and cause NAFLD via accumulation of lipids in liver of developing threespine stickleback (Gasterosteus aculeatus). We performed an upshift/downshift exposure regime (clean water to perchlorate treated water or perchlorate treated water to clean water) on stickleback embryos at two concentrations (30 mg/L and 100 mg/L) plus the control (0 mg/L) over the course of 305 days. Adult stickleback were euthanized, H&E stained and analyzed for liver morphology. Specifically, we counted the number of lipid droplets, and measured the area of each droplet and the total lipid area of a representative section of liver. We found that perchlorate treated fish had more and larger lipid droplets, and a larger percentage of lipid in their liver than control fish. These data indicate that perchlorate causes NAFLD and hepatic steatosis in stickleback at concentrations commonly found at contaminated sites. These data also indicate the potential of perchlorate to act as an obesogen. Future studies should investigate the obesogenic capacity of perchlorate by examining organ specific lipid accumulation and whether perchlorate induces these effects at concentrations commonly found in drinking water. Work is also needed to determine the mechanisms by which perchlorate induces lipid accumulation.


Assuntos
Exposição Ambiental/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Percloratos/toxicidade , Smegmamorpha/metabolismo , Compostos de Sódio/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Feminino , Gotículas Lipídicas/efeitos dos fármacos , Gotículas Lipídicas/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Smegmamorpha/crescimento & desenvolvimento
8.
Scand J Immunol ; 90(3): e12791, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31132306

RESUMO

The epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 epoxygenases and have recently been found to have an anti-inflammatory activity. However, the role of EETs in non-alcoholic steatohepatitis has not been fully understood. In this study, we investigated the protective role of EETs in methionine-choline-deficient (MCD) diet-induced non-alcoholic steatohepatitis (NASH) in mice and the potential mechanisms. We used 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea(TPPU), a soluble epoxide hydrolase inhibitor, to increase the endogenous EET level in mice. Upon TPPU treatment, the liver steatosis and inflammatory damage were significantly ameliorated in mice with steatohepatitis, paralleled by the downregulation of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) as well as chemokines (CXCL1, MCP-1). Compared with untreated NASH mice, mRNA levels of sterol regulatory element binding protein 1c (SREBP1c) and inflammation relevant adhesion molecules (ICAM-1, VCAM-1) were downregulated, whereas mRNA level of peroxisome proliferator-activated receptor α(PPAR-α) was elevated in TPPU-treated mice. In vitro, 11,12-EET treatment remarkably attenuated free fatty acid (FFA)-induced inflammation in HepG2 and THP-1 cells. Further, 11,12-EET inhibited the activation of NF-κB signalling pathway in macrophages from mice with steatohepatitis. Collectively, these results suggest that EETs play a protective role and alleviate the MCD diet-induced steatohepatitis in mice mainly by downregulating activation of NF-κB pathway in macrophages.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Dieta/efeitos adversos , Metionina/metabolismo , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Linhagem Celular , Linhagem Celular Tumoral , Quimiocinas/metabolismo , Colina/metabolismo , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Células Hep G2 , Humanos , Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , PPAR alfa/metabolismo , Compostos de Fenilureia/farmacologia , Piperidinas/farmacologia , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Células THP-1 , Molécula 1 de Adesão de Célula Vascular/metabolismo
9.
J Oleo Sci ; 68(6): 581-589, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31092797

RESUMO

Non-alcoholic fatty liver disease (NAFLD), a common chronic liver disease characterized by hepatic steatosis, affects 30-40% of the population in the world. The seed of Euryale ferox salisb. possesses several pharmacological actions, including metabolic syndrome. However, the seed coat of E. ferox was usually discarded as waste, which contains comparatively abundant polyphenols, and its biological activity has been rarely investigated. In this work, we evaluate the hepatoprotective effect of E. ferox seed coat extract (EFSCE), in NAFLD mice induced by high-fat diet (HFD). The HPLC-MS analysis indicated that the main components of EFSCE were polyphenols. And then, mice were treated with HFD for 4 weeks to induce NAFLD. The result showed that the body weight, weight of adipose tissue, the ratio of liver to body weight in NAFLD mice increased compared with control group. In addition, blood lipids parameters including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL) also increased in NAFLD mouse model. It was showed that, after treated with EFSCE (15 and 30 mg/kg/day) for 4 weeks, the body weight, lipids deposition in the liver and blood lipids in HFD-induced NAFLD mice markedly reduced. Compared with NAFLD mice, EFSCE administration could also prevent malondialdehyde (MDA) overproduction and strengthen Superoxide Dismutase (SOD) activity to counteract oxidative stress. Moreover, EFSCE was also found effective in reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in HFD-induced NAFLD model, which indicated liver injury in NAFLD. Therefore, EFSCE (rich in polyphenols) is indicated as bioactive nature product for HFD-induced NAFLD treatment, by eliminating lipid accumulation and oxidative stress via regulation of IRs-1 and CYP2E1.


Assuntos
Citocromo P-450 CYP2E1/metabolismo , Dieta Hiperlipídica/efeitos adversos , Proteínas Substratos do Receptor de Insulina/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Nymphaeaceae/química , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sementes/química , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Modelos Animais de Doenças , Inibidores Enzimáticos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Polifenóis/análise , Estimulação Química , Superóxido Dismutase/metabolismo
10.
Planta Med ; 85(9-10): 719-728, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31137047

RESUMO

Abnormal lipid metabolism, such as increased fatty acid uptake and esterification, is associated with nonalcoholic fatty liver disease (NAFLD). The aqueous extract of the aerial part of Angelica tenuissima Nakai (ATX) inhibited high-fat diet-induced hepatic steatosis in mice as well as oleic acid-induced neutral lipid accumulation in HepG2 cells. ATX decreased the mRNA and protein levels of CD36 and diglyceride acyltransferase 2 (DGAT2), the maturation of sterol regulatory element-binding proteins (SREBP), and the expression of the lipogenic target genes fasn and scd1. The ATX components, Z-ligustilide and n-butylidenephthalide, inhibited the expression of FATP5 and DGAT2 and thus oleic acid-induced lipid accumulation in HepG2 cells. These results suggest that ATX and its active components Z-ligustilide and n-butylidenephthalide inhibit fatty acid uptake and esterification in mice and have potential as therapeutics for NAFLD.


Assuntos
4-Butirolactona/análogos & derivados , Angelica/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Anidridos Ftálicos/farmacologia , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Animais , Dieta Hiperlipídica/efeitos adversos , Avaliação Pré-Clínica de Medicamentos/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Lipogênese/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácido Oleico/farmacologia , Anidridos Ftálicos/isolamento & purificação , Componentes Aéreos da Planta/química , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
11.
Int J Mol Sci ; 20(9)2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31086120

RESUMO

Kombucha tea (KT) has emerged as a substance that protects the liver from damage; however, its mechanisms of action on the fatty liver remain unclear. Therefore, we investigated the potential role of KT and its underlying mechanisms on nonalcoholic fatty liver disease (NAFLD). db/db mice that were fed methionine/choline-deficient (MCD) diets for seven weeks were treated for vehicle (M + V) or KT (M + K) and fed with MCD for four additional weeks. Histomorphological injury and increased levels of liver enzymes and lipids were evident in the M + V group, whereas these symptoms were ameliorated in the M + K group. The M + K group had more proliferating and less apoptotic hepatocytic cells than the M + V group. Lipid uptake and lipogenesis significantly decreased, and free fatty acid (FFA) oxidation increased in the M + K, when compared with the M + V group. With the reduction of hedgehog signaling, inflammation and fibrosis also declined in the M + K group. Palmitate (PA) treatment increased the accumulation of lipid droplets and decreased the viability of primary hepatocytes, whereas KT suppressed PA-induced damage in these cells by enhancing intracellular lipid disposal. These results suggest that KT protects hepatocytes from lipid toxicity by influencing the lipid metabolism, and it attenuates inflammation and fibrosis, which contributes to liver restoration in mice with NAFLD.


Assuntos
Chá de Kombucha , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Palmitatos/farmacologia , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Proteínas Hedgehog , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Imuno-Histoquímica , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
12.
BMC Complement Altern Med ; 19(1): 92, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035991

RESUMO

BACKGROUND: To investigate the effects of the Alisma and Rhizoma decoction on nonalcoholic steatohepatitis (NASH) and to further shed light on the underlying mechanisms of the actions of the Alisma and Rhizoma decoction. METHODS: Plasma alanine aminotransferase (ALT) content was determined and liver inflammation and fibrosis were evaluated. Intrahepatocellular malondialdehyde and superoxide dismutase contents were determined using commercially available kits Furthermore, α-SMA expression in liver tissues was examined by immunohistochemistry and LC3-II was detected by immunoblotting assays. RESULTS: Mice receiving the Alisma and Rhizoma decoction by gastric lavage had significantly lower plasma ALT content and markedly higher hepatic superoxide dismutase activity than mice receiving the methionine-choline deficient (MCD) diet. Furthermore, the decoction aborted MCD-induced increase in liver malondialdehyde content. Immunohistochemistry showed that the decoction suppressed hepatic α-SMA expression. Our transmission electronic microscopy revealed that the decoction markedly reduced the number of autophagosomes and immunoblotting assays showed that the decoction caused a dose-dependent decrease in LC3-II in hepatic tissues. CONCLUSION: The Alisma and Rhizoma decoction lessens NASH-associated liver injuries by modulating oxidative stress and autophagy in hepatocytes of mice fed with MCD.


Assuntos
Alisma/química , Atractylodes/química , Autofagia/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL
13.
Chem Biol Interact ; 308: 185-193, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31132328

RESUMO

Cytochrome P450 3A (CYP3A) activity is inhibited, and its expression is suppressed during many diseases, including nonalcoholic fatty liver disease (NAFLD). However, the mechanism is controversial. Here, we report that PXR may not take part in the downregulation of CYP3A during NAFLD. Hepatic CYP3A11 (major subtype of mouse CYP3A) mRNA and protein expression was significantly decreased in both mice fed a high-fat diet (HFD) for 8 weeks and palmitate (PA)-treated mouse primary hepatocytes. Similarly, in HepG2 cells, PA treatment significantly suppressed the CYP3A4 (major subtype of human CYP3A) mRNA level and promoter transcription activity. However, Western blotting analysis found an induction of PXR nuclear translocation during NAFLD in both in vivo and in vitro models. Moreover, immunofluorescence determination also found nuclear translocation effect of PXR by PA stimulation in HepG2 cells. In addition, the siRNA knockdown of PXR did not affect the suppressive effects of PA on the CYP3A4 promoter transcription activity and mRNA levels in HepG2 cells. Similarly, PXR knockdown also did not affect the suppressive effects of PA on CYP3A11 mRNA and protein expression levels in mouse primary hepatoctyes. Taken together, the results showed that the suppressive effect of CYP3A transcription was independent of PXR regulation.


Assuntos
Citocromo P-450 CYP3A/metabolismo , Dieta Hiperlipídica , Hepatopatia Gordurosa não Alcoólica/patologia , Receptor de Pregnano X/metabolismo , Animais , Citocromo P-450 CYP3A/genética , Regulação para Baixo/efeitos dos fármacos , Células Hep G2 , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/veterinária , Palmitatos/farmacologia , Receptor de Pregnano X/antagonistas & inibidores , Receptor de Pregnano X/genética , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Transcrição Genética/efeitos dos fármacos
14.
World J Gastroenterol ; 25(14): 1741-1752, 2019 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-31011258

RESUMO

BACKGROUND: Patients with hypothalamic-pituitary disease have the feature of central obesity, insulin resistance, and dyslipidemia, and there is increased prevalence of liver dysfunction consistent with non-alcoholic fatty liver disease (NAFLD) in this population. The causes of hypopituitarism in the reported studies varied and combined pituitary hormone deficiency including central diabetes insipidus is much common in this population. This retrospective cross-sectional study was performed to analyze the clinical characteristics and related factors with NAFLD and cirrhosis in Chinese adult hypopituitary/panhypopituitary patients. AIM: To analyze the clinical characteristics of and related risk factors for NAFLD in Chinese adult hypopituitary patients. METHODS: Adult Chinese patients with hypopituitarism and/or panhypopituitarism were enrolled at the Pituitary Center of Peking Union Medical College Hospital between August 2012 and April 2018. According to abdominal ultrasonography, these patients were divided into an NAFLD (-) group and an NAFLD (+) group, and the latter was further divided into an NAFLD group and a cirrhotic group. The data, such as patient characteristics, diagnosis, and treatment, were extracted from medical records, and statistical analysis was performed. RESULTS: A total of 36 male and 14 female adult Chinese patients with hypopituitarism were included in this retrospective study; 43 (87.0%) of these patients exhibited growth hormone (GH) deficiency, and 39 (78.3%) had diabetes insipidus. A total of 27 (54.0%) patients were diagnosed with NAFLD, while seven patients were cirrhotic. No significant differences were noted in serum GH or insulin-like growth factor 1 among patients with cirrhosis, subjects with NAFLD, and those without NAFLD. However, plasma osmolality and serum sodium concentration of the cirrhotic patients were 314.9 mOsm/kgH2O and 151.0 mmol/L, respectively, which were significantly higher than those of the NAFLD patients (P = 0.036 and 0.042, respectively). Overweight/obesity and insulin resistance were common metabolic disorders in this population. The body mass index (BMI) and homeostasis model assessment of insulin resistance parameters of the cirrhotic patients were 27.7 kg/m2 and 9.57, respectively, which were significantly higher than those of the patients without NAFLD (P = 0.011 and 0.044, respectively). A correlation analysis was performed, and fasting insulin concentration was positively associated with plasma osmolality in patients with NAFLD, after adjusting for gender, age, and BMI (r = 0.540, P = 0.046), but no correlation was noted in patients without NAFLD. CONCLUSION: NAFLD is common in patients with hypopituitarism. Plasma osmolality and serum sodium levels of hypopituitary patients with cirrhosis are higher than those of subjects with NAFLD, and fasting insulin concentration is positively associated with plasma osmolality in patients with NAFLD, which suggests that hyperosmolality might be a contributor to the worsening of NAFLD in hypopituitary patients.


Assuntos
Hipopituitarismo/metabolismo , Cirrose Hepática/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Hipopituitarismo/sangue , Insulina/sangue , Cirrose Hepática/sangue , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Concentração Osmolar , Plasma/química , Prevalência , Estudos Retrospectivos , Fatores de Risco , Sódio/sangue , Adulto Jovem
15.
Anal Cell Pathol (Amst) ; 2019: 2013674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31011515

RESUMO

Supersonic shear imaging (SSI) is a relatively new technique to measure the elasticity of target tissues based on the shear wave propagation. The aim of this study was to evaluate the value of SSI in discriminating nonfibrotic nonalcoholic steatohepatitis (NASH) from the less severe nonalcoholic fatty liver disease (NAFLD), NASH with fibrosis, and the normal liver, as well as the relationship between various NAFLD pathologic or biochemical findings and SSI liver elasticity. Rabbits with NAFLD of different degrees were subjected to SSI for liver elasticity measurement. Plasma was collected for biochemical examinations, and liver tissues were harvested for pathologic assessment. Results showed that liver elasticity of rabbits with nonfibrotic NASH was significantly different from that of rabbits with simple steatosis, borderline, NASH with fibrosis, and normal liver (P < 0.05) and the areas under the receiver operating characteristic curve of SSI for predicting nonfibrotic NASH and NASH with fibrosis were 0.997 and 0.967, respectively, and the optimal cutoff values were 10.17 kPa and 12.82 kPa, respectively. Multivariate analysis showed that only fibrosis and inflammation were the independent factors affecting liver elasticity of NAFLD (P ≤ 0.001), while inflammation, steatosis, and ballooning degeneration were all independently related to liver elasticity in rabbits without fibrosis (P < 0.01). In addition, alanine aminotransferase was the only biochemical factor independently related to liver elasticity (P ≤ 0.001). Our results indicate that SSI can effectively identify nonfibrotic NASH in rabbits based on the difference in liver elasticity and the difference is related to the various pathologic changes, including fibrosis, inflammation, steatosis, and ballooning degeneration.


Assuntos
Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Fígado/metabolismo , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Cirrose Hepática/sangue , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Curva ROC , Coelhos
16.
Int J Mol Med ; 43(6): 2398-2408, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30942432

RESUMO

Oxaliplatin (OXA)­based chemotherapy is widely used in the treatment of gastrointestinal tumors; however, it is associated with chemotherapy­associated liver injury. Whether OXA induces liver injury and aggravates the already existing hepatic oxidative stress, inflammation and fibrosis in non­alcoholic fatty liver disease (NAFLD), and whether these effects can be alleviated by reduced glutathione (GSH) treatment, remains unclear. In the present study, OXA induced acute liver injury in NAFLD mice. Moreover, OXA increased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased the levels of superoxide dismutase and GSH peroxidase in the livers of NAFLD mice. OXA also induced the upregulation of hepatic inflammatory cytokines, such as tumor necrosis factor (TNF)­α, interferon (IFN)­Î³ and interleukin (IL)­17, in NAFLD mice. Furthermore, collagen fiber deposition in liver tissues was increased and the expression of transforming growth factor (TGF)­ß, α­smooth muscle actin (SMA) and tissue inhibitor of metallopeptidase (TIMP)­1 was upregulated in the livers of OXA­treated NAFLD mice. Treatment with exogenous GSH alleviated OXA­induced acute liver injury in NAFLD mice, and significantly reduced the levels of ROS, MDA and TNF­α. However, GSH treatment did not inhibit collagen fiber deposition, although it reduced the levels of IFN­Î³, IL­17, TGF­ß, α­SMA and TIMP­1 in the livers of OXA­treated NAFLD mice. In conclusion, OXA chemotherapy may induce acute liver injury and aggravate the existing hepatic oxidative stress, inflammation and fibrosis in NAFLD. Treatment of NAFLD mice with exogenous GSH alleviated OXA­induced liver injury, possibly by ameliorating OXA­aggravated hepatic oxidative stress and inflammation; it did not, however, attenuate OXA­aggravated liver fibrosis.


Assuntos
Antineoplásicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/patologia , Oxaliplatina/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Glutationa/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Camundongos , Camundongos Endogâmicos BALB C , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo
17.
Math Biosci Eng ; 16(3): 1082-1114, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30947410

RESUMO

Non-alcoholic fatty liver disease is the most common cause of chronic liver disease. Precipitated by the build up of extra fat in the liver not caused by alcohol, it is still not understood why steatosis occurs where it does in the liver microstructure in non-alcoholic fatty liver disease. It is likely, however, that the location of steatosis is due, at least in part, to metabolic zonation (heterogeneity among liver cells in function and enzyme expression). Recently, there has been an influx of computational and mathematical models in order to investigate the relationship between metabolic zonation and steatosis in non-alcoholic fatty liver disease. Of interest among these models are "compartments-in-series" models. Compartments-in-series models include the spatial distribution of metabolite concentrations via series of compartments that are connected through some representation of blood flow. In this paper, we analyze one such model, focusing specifically at how the number of compartments and inclusion of dispersion in the flow affect simulation results. We find the number of compartments to have a much larger effect than the inclusion of dispersion, however this is likely due to numerical artifacts. Overall, we conclude that considering partial differential equations that are equivalent to compartments-in-series models would be beneficial both in computation and in theoretical analyses.


Assuntos
Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Tecido Adiposo/metabolismo , Alimentos , Glucose/farmacocinética , Hepatócitos/metabolismo , Humanos , Insulina/metabolismo , Metabolismo dos Lipídeos , Lipólise , Fígado/irrigação sanguínea , Modelos Biológicos , Hepatopatia Gordurosa não Alcoólica/metabolismo
18.
Phytomedicine ; 59: 152782, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31005808

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. Swertia bimaculata (Sieb. et Zucc.) Hook. Thoms.ex Clarke, a glabrous or procumbent perennial herb, is a traditional herb medicine. Swertiamarin, a secoiridoid glycoside, is a representative ingredient in this medical plant crude extract and shows antidiabetic and antihyperlipidaemic activities and protective effect against hepatic injury. PURPOSE: The present study aimed to determine whether swertiamarin can attenuate NAFLD in fructose-fed mice. METHODS: Healthy male mice freely drank water containing 10% fructose for 12 consecutive weeks, whereas animals in those swertiamarin tested groups received different doses of swertiamarin (25, 50 and 100 mg/kg) by intragastric administration once a day from the ninth week to the twelfth week. RESULTS: At the end of the experiment, fructose-fed mice administrated with swertiamarin showed low levels of serum glucose, triglycerides, uric acid, alanine aminotransferase and aspartate transaminase. Histological examinations suggested the alleviation of hepatic ballooning degeneration and steatosis by swertiamarin treatment. Moreover, swertiamarin administration mitigated hepatic oxidative stress along with decreases of hepatic pro-inflammation cytokines, which was associated with decrease of hepatic xanthine oxidase (XO) activity and enhancements of anti-oxidant defense system enzymes, as well as activation of nuclear factor E2-related factor 2 (Nrf2) in fructose-fed mice. In addition, swertiamarin down-regulated expression of sterol-regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1) in liver of fructose-fed mice. CONCLUSION: The present study demonstrates that swertiamarin alleviates NAFLD and metabolic alterations in fructose-fed mice.


Assuntos
Frutose/efeitos adversos , Glucosídeos Iridoides/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Pironas/farmacologia , Acetil-CoA Carboxilase/metabolismo , Alanina Transaminase/metabolismo , Animais , Citocinas/metabolismo , Ácido Graxo Sintases/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Xantina Oxidase/metabolismo
19.
Int J Mol Sci ; 20(8)2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31018538

RESUMO

Non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is the most common chronic liver disease in the world. However, there are still no drugs for NAFLD/NASH in the market. Gastrodin (GAS) is a bioactive compound that is extracted from Gastrodia elata, which is used as an active compound on nervous system diseases. Recent reports showed that GAS and Gastrodia elata possess anti-oxidant activity and lipid regulating effects, which makes us curious to reveal the anti-NAFLD effect of GAS. A high cholesterol diet (HCD) was used to induce a NAFLD larval zebrafish model, and the lipid regulation and anti-oxidant effects were tested on the model. Furthermore, qRT-PCR studied the underlying mechanism of GAS. To conclude, this study revealed a lipid regulation and anti-oxidant insights of GAS on NAFLD larval zebrafish model and provided a potential therapeutic compound for NAFLD treatment.


Assuntos
Antioxidantes/uso terapêutico , Álcoois Benzílicos/uso terapêutico , Gastrodia/química , Glucosídeos/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Antioxidantes/isolamento & purificação , Álcoois Benzílicos/isolamento & purificação , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/isolamento & purificação , Larva/efeitos dos fármacos , Larva/genética , Larva/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
20.
Int J Mol Sci ; 20(7)2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30970564

RESUMO

Hepatocellular carcinoma (HCC) is one of the most widespread tumors in the world and its prognosis is poor because of lack of effective treatments. Epidemiological studies show that non-alcoholic steatohepatitis (NASH) and advanced fibrosis represent a relevant risk factors to the HCC development. However little is known of pathophysiological mechanisms linking liver fibrogenesis to HCC in NASH. Recent advances in scientific research allowed to discover some mechanisms that may represent potential therapeutic targets. These include the integrin signaling, hepatic stellate cells (HSCs) activation, Hedgehog signaling and alteration of immune system. In the near future, knowledge of fibrosis-dependent carcinogenic mechanisms, will help optimize antifibrotic therapies as an approach to prevent and treat HCC in patients with NASH and advanced fibrosis.


Assuntos
Carcinoma Hepatocelular/metabolismo , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Carcinoma Hepatocelular/etiologia , Hipóxia Celular , Progressão da Doença , Proteínas Hedgehog/metabolismo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Humanos , Integrinas/metabolismo , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Transdução de Sinais
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