scholarly journals Ethyl Acetate Fraction of Amomum villosum var. xanthioides Attenuates Hepatic Endoplasmic Reticulum Stress-Induced Non-Alcoholic Steatohepatitis via Improvement of Antioxidant Capacities

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 998
Author(s):  
Jung-Hyo Cho ◽  
Jong-Suk Lee ◽  
Hyeong-Geug Kim ◽  
Hye Won Lee ◽  
Zhigang Fang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Liver ◽  
Ethyl Acetate ◽  
Er Stress ◽  
Antioxidant Properties ◽  
Ethyl Acetate Fraction ◽  
Hepatic Tissue ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Amomum Villosum

Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH), affects 25% of the global population. Despite the prevalence of NAFLD worldwide, effective therapeutics are currently lacking. Amomum villosum var. xanthioides (Wall. ex Baker) T.L.Wu & S.J.Chen (AX) is a medicinal herb traditionally used for treating digestive tract disorders in countries across Asia. We aimed to examine the pharmacological effects of the ethyl acetate fraction of AX (AXEF) against tunicamycin (TM)-induced ER stress in a NASH mouse model using C57/BL6J male mice. Following TM injections (2 mg/kg), the mice were orally administrated AXEF (12.5, 25, or 50 mg/kg), silymarin (50 mg/kg), or distilled water daily for 5 days, and the outcomes for fatty liver, inflammation, and oxidative stress were measured in serum or liver tissue levels. AXEF drastically attenuated hepatic ER stress-induced NASH as indicated by decreases in lipid droplet accumulations, serum liver enzymes, hepatic inflammations, and cell death signals in the hepatic tissue and/or serum levels. Interestingly, AXEF showed potent antioxidant effects by quenching reactive oxidative stress and its final product lipid peroxide in the hepatic tissue, specifically an increase in metallothionein (MT). To confirm the underlying actions of AXEF, we observed that AXEF increases MT1 gene promoter activities in the physiological levels. Collectively, AXEF showed antioxidant properties on TM-induced ER stress in a NASH mice model through the improvement of MTs.

scholarly journals Metabolomic Predictors of Non-alcoholic Steatohepatitis and Advanced Fibrosis in Children

2021 ◽  
Vol 12 ◽  
Author(s):  
Kattayoun Kordy ◽  
Fan Li ◽  
David J. Lee ◽  
Jason M. Kinchen ◽  
Michael H. Jew ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Mitochondrial Dysfunction ◽  
Carbon Metabolism ◽  
Fatty Liver Disease ◽  
Plasma Metabolites ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
One Carbon Metabolism

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in western countries both in children and adults. Metabolic dysregulation associated with gut microbial dysbiosis may influence disease progression from hepatic steatosis to inflammation and subsequent fibrosis. Using a multi-omics approach, we profiled the oral and fecal microbiome and plasma metabolites from 241 predominantly Latino children with non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver (NAFL), and controls. Children with more severe liver pathology were dysbiotic and had increased gene content associated with lipopolysaccharide biosynthesis and lipid, amino acid and carbohydrate metabolism. These changes were driven by increases in Bacteroides and concomitant decreases of Akkermansia, Anaerococcus, Corynebacterium, and Finegoldia. Non-targeted mass spectrometry revealed perturbations in one-carbon metabolism, mitochondrial dysfunction, and increased oxidative stress in children with steatohepatitis and fibrosis. Random forests modeling of plasma metabolites was highly predictive of non-alcoholic steatohepatitis (NASH) (97% accuracy) and hepatic fibrosis, steatosis and lobular inflammation (93.8% accuracy), and can differentiate steatohepatitis from simple steatosis (90.0% accuracy). Multi-omics predictive models for disease and histology findings revealed perturbations in one-carbon metabolism, mitochondrial dysfunction, and increased oxidative stress in children with steatohepatitis and fibrosis. These results highlight the promise of non-invasive biomarkers for the growing epidemic of fatty liver disease.

scholarly journals Perubahan Mikrostruktur Jaringan Hati pada Mencit Model Sindrom Metabolik yang Diberi Fraksi Zingiber officinale

2019 ◽  
Vol 1 (1) ◽  
pp. 25-31
Author(s):  
Dilla Latul Anjaniah ◽  
Eka Nurhayati ◽  
Herry Garna ◽  
Annisa Rahmah Furqaani ◽  
Maya Tejasari
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Ethyl Acetate ◽  
Liver Tissue ◽  
Fatty Liver Disease ◽  
Zingiber Officinale ◽  
Ethyl Acetate Fraction ◽  
Mice Model ◽  
Alcoholic Fatty Liver

Non-alcoholic fatty liver disease (NAFLD) merupakan penyakit perlemakan pada hati yang terjadi pada penderita sindrom metabolik. Penderita sindrom metabolik terjadi peningkatan kadar stres oksidatif sehingga muncul sel steatosis dan pelebaran sinusoid hati. Senyawa flavonoid dalam Zingiber officinale (jahe gajah) diketahui memiliki efek hepatoprotektif dan antiinflamasi dengan cara menghambat pembentukan reactive oxygen species (ROS). Tujuan penelitian ini mengetahui pengaruh  fraksi etil asetat jahe gajah terhadap mikrostruktur jaringan hati pada mencit model sindrom metabolik. Objek penelitian ini menggunakan mencit jantan galur Swiss Webster yang berusia 36−40 minggu dibagi menjadi 4 kelompok. Penelitian dilakukan di Laboratorium Farmasi Institut Teknologi Bandung. Kelompok kontrol yang diberi pakan tinggi lemak tanpa diberikan terapi selama 28 hari. Kelompok II−IV diberi pakan tinggi lemak dan diterapi dengan diberi fraksi etil asetat jahe gajah dengan konsentrasi 0,78 mg, 1,56 mg,  dan 3,12 mg per kilogram bobot per hari diberikan secara oral. Observasi dan kuantifikasi mikrostruktur jaringan hati dilakukan menggunakan mikroskop cahaya. Hasil statistik jumlah sel steatosis belum menunjukkan hasil yang signifikan (p>0,05), sedangkan pada jumlah pelebaran sinusoid menunjukkan hasil yang signifikan (p<0,05).   Kekuatan korelasi konsentrasi fraksi jahe gajah dengan jumlah sel steatosis rendah, tetapi pasti (r=-0,381)  dan pelebaran sinusoid cukup berarti (r=-0,451). Simpulan penelitian ini adalah pemberian fraksi etil asetat jahe gajah memengaruhi mikrostruktur jaringan hati pada mencit model sindrom metabolik. LIVER TISSUE MORPHOLOGICAL CHANGES BY ZINGIBER OFFICINALE FRACTIONS IN METABOLIC SYNDROME MICE MODELSNon-alcoholic fatty liver disease (NAFLD) is a fatty liver disease that occurs in patients with metabolic syndrome. Patients with metabolic syndrome occur closer to oxidative stress that occurs in steatosis and dilation of the liver sinusoid. Flavonoid compounds in Zingiber officinale have hepatoprotective and anti inflammatory effects by inhibiting the formation of reactive oxygen species (ROS). The purpose of this study was to determine the content of Zingiber officinale ethyl acetate fraction on liver tissue microstructure in mice model of metabolic syndrome. This research method using mice of Swiss webster strain which had 36−40 weeks, divided into 4 groups. The study  conducted at Pharmacology Laboratory Institut Teknologi Bandung. Control group fed high fat without therapy for 28 days. Group II−IV were fed high fat and treated with ginger elephant ethyl acetate fraction with a concentration of 0.78 mg, 1.56 mg and 3.12 mg per kilograms of body weight per day, given orally. Observation and quantification of liver tissue microstructure was performed using a light microscope. The statistical results on steatosis cell counts did not show significant results (p>0.05), whereas the number of sinusoid enlargement showed significant results (p<0.05). Alternative strength of the Zingiber officinale fraction with a low but definite steatosis cell number (r=−0.381) and significant sinusoid widening (r=−0.451). In conclusion, that administration of ginger elephant ethyl acetate fraction affected microstructure of liver tissue in mice model of metabolic syndrome.

scholarly journals Beneficial effects of N-acetylcysteine on hepatic oxidative stress in streptozotocin-induced diabetic rats

2018 ◽  
Vol 96 (4) ◽  
pp. 412-418 ◽  
Author(s):  
Lucas Rodolfo de Oliveira Rosa ◽  
Anderson Kiyoshi Kaga ◽  
Pedro Octavio Barbanera ◽  
Priscila Manfio Queiroz ◽  
Nágilla Orleanne Lima do Carmo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Properties ◽  
Diabetic Complication ◽  
Diabetic Rats ◽  
Hepatic Tissue ◽  
Diabetes Research ◽  
Oxidative Stress Biomarkers ◽  
Alcoholic Fatty Liver ◽  
Hepatic Oxidative Stress ◽  
And Oxidative Stress

Diabetes is one of the leading diseases worldwide and, thus, finding new therapeutic alternatives is essential. The development of non-alcoholic fatty liver disease is a notable diabetic complication. Therefore, antioxidant therapy became a leading topic in the world of diabetes research. The objective of this present study was to evaluate the effects of antioxidant N-acetylcysteine (NAC) administration on serum biochemical parameters and oxidative stress parameters in hepatic tissue of the diabetic rats. Thirty-two animals were divided in 4 groups (n = 8): G1, normal rats; G2, normal rats + NAC; G3, diabetic rats; and G4, diabetic rats + NAC. Diabetes was induced in diabetic groups through streptozotocin. NAC administration was effective in improving hyperglycemia and hypoinsulinemia, as well as reducing serum alanine-aminotransferase and urea, hepatic triglycerides accumulation, and oxidative stress biomarkers in the diabetic liver, as well as improving the activity of hepatic antioxidant enzymes. This effect was likely due to NAC’s ability of restoring intracellular glutathione, an important compound for the antioxidant defense, as well as due to NAC’s direct antioxidant properties. Thus, NAC administration was useful for reducing hepatic oxidative stress and decreased the deposit of triacylglycerols, minimizing diabetic hepatic damage, making it a promising therapeutic adjuvant in the future.

Resveratrol Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-analysis

2017 ◽  
Vol 26 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Ahmed Elgebaly ◽  
Ibrahim A. I. Radwan ◽  
Mohamed M. AboElnas ◽  
Hamza H. Ibrahim ◽  
Moutaz F. M. Eltoomy ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Randomized Clinical Trials ◽  
Controlled Trial ◽  
Antioxidant Properties ◽  
Density Lipoprotein ◽  
Current Evidence ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Background: Resveratrol is a potential treatment option for management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant properties, and calorie restriction-like effects. We aimed to synthesise evidence from published randomized clinical trials (RCTs) about the efficacy of resveratrol in the management of NAFLD.Methods: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup analysis and sensitivity analysis were conducted.Results: Four RCTs (n=158 patients) were included in the final analysis. The overall effect estimates did not favor resveratrol group in terms of: serum ALT (MD -2.89, 95%CI [-15.66, 9.88], p=0.66), serum AST (MD -3.59, 95%CI [-13.82, 6.63], p=0.49), weight (MD -0.18, 95%CI [-0.92, 0.55], p=0.63), BMI (MD -0.10, 95 %CI [-0.43, 0.24], p=0.57), blood glucose level (MD -0.27, 95%CI [-0.55, 0.01], p=0.05), insulin level (MD -0.12, 95%CI [-0.69, 0.46], p=0.69), triglyceride level (MD 0.04, 95%CI [-0.45, 0.53], p=0.87), and LDL level (MD 0.21, 95%CI [-0.41, 0.83], p=0.51). Pooled studies were heterogeneous.Conclusion: Current evidence is insufficient to support the efficacy of resveratrol in the management of NAFLD. Resveratrol does not attenuate the degree of liver fibrosis or show a significant decrease in any of its parameters.Abbreviations: ALT: Alanine aminotransferase; AMPK: AMP-activated protein kinase; AST: Aspartate aminotransferase; BMI: Body mass index; CK-18: Cytokeratin-18; CRP: C-reactive protein; HC: Head circumference; HDL: High density lipoprotein; IL-6: Interleukin-6; LDL: Low density lipoprotein; MD: Mean difference; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; RCT: Randomized Controlled Trial; RR: Relative risk; SIRT1: Silent information regulation 2 homologue 1; TNF-α: Tumor necrosis factor α; WC: Waist circumference; WHR: Waist hip ratio.

New therapy for fatty liver

2018 ◽  
Vol 1 (2) ◽  
pp. 24-28
Author(s):  
Tanita Suttichaimongkol
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Lifestyle Modifications ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Liver Insulin Resistance ◽  
Alcoholic Fatty Liver Disease ◽  
Related Mortality

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of death from liver cirrhosis, endstage liver disease, and hepatocellular carcinoma. It is also associated with increased cardiovasculardisease and cancer related mortality. While lifestyle modifications are the mainstay of treatment,only a proportion of patients are able to make due to difficult to achieve and maintain, and so moretreatment options are required such as pharmacotherapy. This review presents the drugs used inmanaging NAFLD and their pharmacologic targets. Therapies are currently directed towards improvingthe metabolic status of the liver, insulin resistance, cell oxidative stress, apoptosis, inflammation orfibrosis. Several agents are now in large clinical trials and within the next few years, the availability oftherapeutic options for NAFLD will be approved.     Keywords: nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, fibrosis, cirrhosis  

Natural Aldose Reductase Inhibitor: A Potential Therapeutic Agent for Non-alcoholic Fatty Liver Disease

2020 ◽  
Vol 21 (6) ◽  
pp. 599-609 ◽  
Author(s):  
Longxin Qiu ◽  
Chang Guo
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Aldose Reductase ◽  
Fatty Liver Disease ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver

Aldose reductase (AR) has been reported to be involved in the development of nonalcoholic fatty liver disease (NAFLD). Hepatic AR is induced under hyperglycemia condition and converts excess glucose to lipogenic fructose, which contributes in part to the accumulation of fat in the liver cells of diabetes rodents. In addition, the hyperglycemia-induced AR or nutrition-induced AR causes suppression of the transcriptional activity of peroxisome proliferator-activated receptor (PPAR) α and reduced lipolysis in the liver, which also contribute to the development of NAFLD. Moreover, AR induction in non-alcoholic steatohepatitis (NASH) may aggravate oxidative stress and the expression of inflammatory cytokines in the liver. Here, we summarize the knowledge on AR inhibitors of plant origin and review the effect of some plant-derived AR inhibitors on NAFLD/NASH in rodents. Natural AR inhibitors may improve NAFLD at least in part through attenuating oxidative stress and inflammatory cytokine expression. Some of the natural AR inhibitors have been reported to attenuate hepatic steatosis through the regulation of PPARα-mediated fatty acid oxidation. In this review, we propose that the natural AR inhibitors are potential therapeutic agents for NAFLD.

Prevalence, diagnosis and treatment with 3 different statins of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in military personnel. Do genetics play a role?

2020 ◽  
Vol 18 ◽  
Author(s):  
Georgios Sfikas ◽  
Michael Psallas ◽  
Charalambos Koumaras ◽  
Konstantinos Imprialos ◽  
Evangelos Perdikakis ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Military Personnel ◽  
Fatty Liver Disease ◽  
Exercise Group ◽  
Severe Form ◽  
Laboratory Evaluation ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), are major health problems worldwide. Genetics may play a role in the pathogenesis of NAFLD/NASH. Aim: To investigate the prevalence of NAFLD/NASH in 5,400 military personnel and evaluate the effect of treatment with 3 statins on NAFLD/NASH using 2 non-invasive scores [NAFLD Activity Score (NAS); Fibrosis-4 score (FIB-4)]. Methods: During the mandatory annual medical check-up, military personnel underwent a clinical and laboratory evaluation. Participants with NAFLD/NASH were randomised to 4 groups (n=151 each): dietexercise, atorvastatin, rosuvastatin or pitavastatin for 1 year (i.e. until the next routine evaluation). Results: From all the participants, 613 had NAFLD/NASH (prevalence 11.3 vs 39.8% in the general population, p<0.001); 604 consented to participate in the study. After a year of treatment, the diet-exercise group showed no significant changes in both scores (NAS 4.98 baseline vs 5.62, p=0.07; FIB-4 3.42 vs 3.52, p=0.7). For the atorvastatin group, both scores were reduced (NAS 4.97 vs 1.95, p<0.001, FIB-4 3.56 vs 0.83, p<0.001), for rosuvastatin (NAS 5.55 vs 1.81, p<0.001, FIB-4 3.61 vs 0.79, p<0.001), and for pitavastatin (NAS 4.89 vs 1.99, p<0.001, FIB-4 3.78 vs 0.87, p<0.001). Conclusions : Atorvastatin, rosuvastatin and pitavastatin have a beneficial and safe effect in NAFLD/NASH patients as recorded by the improvement in the NAS (representing NAFLD activity) and FIB-4 (representing liver fibrosis) scores. Since both those with and without NAFLD/NASH shared several baseline characteristics, genetics may play a role in the pathogenesis of NAFLD/NASH and its treatment with statins.

scholarly journals Paraoxonase 1 and Non-Alcoholic Fatty Liver Disease: A Meta-Analysis

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2323
Author(s):  
Kazuhiko Kotani ◽  
Jun Watanabe ◽  
Kouichi Miura ◽  
Alejandro Gugliucci
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Laboratory Data ◽  
Paraoxonase 1 ◽  
Mixed Data ◽  
Alcoholic Fatty Liver ◽  
Paraoxonase Activity

Oxidative stress is involved in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). However, reliable biomarkers of NAFLD in relation to oxidative stress are not available. While paraoxonase 1 (PON1) is an antioxidant biomarker, there appears to be mixed data on PON-1 in patients with NAFLD. The aim of this meta-analysis was to assess the current data on PON1 activity (i.e., paraoxonase and arylesterase) in patients with NAFLD. A PubMed, CENTRAL, and Embase search identified 12 eligible articles. In the meta-analysis, the paraoxonase activity was low in patients with NAFLD (mean difference (MD) −27.17 U/L; 95% confidence interval (CI) −37.31 to −17.03). No difference was noted in the arylesterase activity (MD 2.45 U/L; 95% CI −39.83 to 44.74). In a subgroup analysis, the paraoxonase activity was low in biopsy-proven nonalcoholic steatohepatitis (MD −92.11 U/L; 95% CI −115.11 to −69.11), while the activity in NAFLD as diagnosed by ultrasonography or laboratory data was similar (MD −2.91 U/L; 95% CI −11.63 to 5.80) to that of non-NAFLD. In summary, the PON1, especially paraoxonase, activity could be a useful biomarker of NAFLD. Further studies are warranted to ascertain the relevance of PON1 measurements in patients with NAFLD.

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