scholarly journals Gynostemma pentaphyllum Attenuates the Progression of Nonalcoholic Fatty Liver Disease in Mice: A Biomedical Investigation Integrated with In Silico Assay

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Ming Hong ◽  
Zhe Cai ◽  
Lei Song ◽  
Yongqiang Liu ◽  
Qi Wang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
In Silico ◽  
Fatty Liver Disease ◽  
Critical Role ◽  
Network Pharmacology ◽  
Gynostemma Pentaphyllum ◽  
Nonalcoholic Fatty Liver ◽  
Mitochondrial Fatty Acid

Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease in developed countries. Oxidative stress plays a critical role in the progression of NAFLD. Modern pharmacological study and clinical trials have demonstrated the remarkable antioxidant activity of Gynostemma pentaphyllum (GP) in chronic liver disease. One aim of this study was to explore the potential protective effects and mechanisms of action of GP extract on NAFLD. The in vivo results showed that GP extract could alleviate fatty degeneration and haptic fibrosis in NAFLD mice. For exploring the hepatoprotective mechanisms of GP, we used network pharmacology to predict the potential active components of GP and their intracellular targets in NAFLD. Based on the network pharmacology results, we further utilized biomedical assays to validate this in silico prediction. The results showed that Gypenoside XL could upregulate the protein level of PPARα in NAFLD; the transcription level of several PPARα downstream target genes such as acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase-1 (CPT-1) also increased after Gypenoside XL treatment. The overexpression of ACO and CPT-1 may involve the hepatoprotective effects of GP and Gypenoside XL on NAFLD by regulating mitochondrial fatty acid β-oxidation.

scholarly journals Network Pharmacology-Based Analysis of Pogostemon cablin (Blanco) Benth Beneficial Effects to Alleviate Nonalcoholic Fatty Liver Disease in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Yizhe Cui ◽  
Qiuju Wang ◽  
Renxu Chang ◽  
Ahmad Aboragah ◽  
Juan J. Loor ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Network Pharmacology ◽  
Nonalcoholic Fatty Liver ◽  
Pogostemon Cablin ◽  
Anti Oxidant ◽  
Anti Inflammatory

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is associated with high morbidity and mortality. Pogostemon cablin (Blanco) Benth/Huo Xiang (HX) is a perennial herb with unique anti-oxidant and anti-inflammatory properties, and thus, can positively affect liver function. In this study, we used network pharmacology to predict the potential mechanism of HX on NAFLD. Pharmacological experiments were used to verify the effect of HX on the functions of NAFLD. Network pharmacology identified nine components that interacted with 82 NAFLD-related targets, revealing four target genes: TNF, IL6, TP53, and AKT1. HX prevents the development and progression of NAFLD through different pathways and targets with quercetin-regulated lipid metabolism, anti-inflammatory, and anti-oxidant pathways playing an essential role in the treatment of NAFLD. Compared with feeding HFD, HX significantly attenuated lipid accumulation in vivo with mice and also in vitro with mouse liver cells. A high dose of HX decreased hepatocyte lipid accumulation and the abundance of SREBF1 and FASN. Validation experiments revealed that HX inhibited the activation of NF-κB/IκB signaling and decreased the release and levels of pro-inflammatory factors (TNF-α and IL-6). These data suggest that HX can attenuate abnormal lipid metabolic responses and enhance antioxidant mechanisms. Thus, the pharmacological effects from plants used in traditional Chinese medicine are achievde through a multi-level response.

Natural modulators of nonalcoholic fatty liver disease: Mode of action analysis and in silico ADME-Tox prediction

2017 ◽  
Vol 337 ◽  
pp. 45-66 ◽  
Author(s):  
Merilin Al Sharif ◽  
Petko Alov ◽  
Vessela Vitcheva ◽  
Antonia Diukendjieva ◽  
Mattia Mori ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Mode Of Action ◽  
In Silico ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Action Analysis

scholarly journals Regulation of mitochondrial trifunctional protein modulates nonalcoholic fatty liver disease in mice

2018 ◽  
Vol 59 (6) ◽  
pp. 967-973 ◽  
Author(s):  
Fatiha Nassir ◽  
Justin J. Arndt ◽  
Sarah A. Johnson ◽  
Jamal A. Ibdah
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
Mitochondrial Function ◽  
Fatty Liver Disease ◽  
Critical Role ◽  
Acid Oxidation ◽  
Nonalcoholic Fatty Liver ◽  
Mitochondrial Trifunctional Protein

Mitochondrial trifunctional protein (MTP) plays a critical role in the oxidation of long-chain fatty acids. We previously reported that aging mice (>9 months old) heterozygous for an MTP defect (MTP+/−) develop nonalcoholic fatty liver disease (NAFLD). We tested whether a high-fat diet (HFD) accelerates NAFLD in young MTP+/−mice, and whether overexpression of the nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase sirtuin 3 (SIRT3) deacetylates MTP and improves mitochondrial function and NAFLD. Three-month-old WT and MTP+/− mice were fed HFD (60% cal fat) for 16 weeks and livers were assessed for fatty acid oxidation (FAO) and NAFLD. Compared with WT, MTP+/− mice displayed reduced hepatic SIRT3 levels and reduced FAO, with increased hepatic steatosis and the inflammatory marker CD68. Hepatic overexpression of SIRT3 in HFD-fed MTP+/− mice increased hepatic MTP protein levels at the posttranscriptional level. Immunoprecipitation of MTP from liver mitochondria followed by Western blot with acetyl-lysine antibody showed higher acetylation of MTP in MTP+/− compared with WT mice. Overexpression of SIRT3 in MTP+/− mice significantly reduced the acetylation of MTP compared with β-galactosidase controls, increased mitochondrial FAO, and reduced hepatic steatosis, CD68, and serum ALT levels. Taken together, our data indicate that deacetylation of MTP by SIRT3 improves mitochondrial function and rescues NAFLD in MTP+/− mice.

scholarly journals Research on the Mechanism of Qushi Huayu Decoction in the Intervention of Nonalcoholic Fatty Liver Disease Based on Network Pharmacology and Molecular Docking Technology

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Shan-shan Gao ◽  
Ji-jia Sun ◽  
Xin Wang ◽  
Yi-yang Hu ◽  
Qin Feng ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathway ◽  
Active Ingredient ◽  
Fatty Liver Disease ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Nonalcoholic Fatty Liver

Objective. To use network pharmacology and molecular docking technology in predicting the main active ingredients and targets of Qushi Huayu Decoction (QHD) treatment in Nonalcoholic Fatty Liver Disease (NAFLD) and explore the potential mechanisms of its multi-component-multi-target-multi-pathway. Materials and Methods. The main chemical components of QHD were searched using traditional Chinese medicine system pharmacology technology platform (TCMSP) and PubChem database. The main chemical components of the prescription were ADMET screened by the ACD/Labs software. The main active ingredient was screened by 60% oral bioavailability, and 60% of “bad” ingredients were removed from the drug-like group. Swiss Target Prediction, the SEA, and HitPick systems were sequentially used to search for the target of each active ingredient, and a network map of the QHD’s target of the active ingredient was constructed. Genome annotation database platforms (GeneCards, OMIM, and DisGeNET) were used to predict action targets related to fatty liver disease. “Drug-Disease-Target” network diagram could be visualized with the help of Cytoscape (3.7.1) software. UniProt and STRING database platforms were used to build a protein interaction network. The KEGG signal pathway and DAVID platform were analyzed for biological process enrichment. Results. A total of 128 active ingredients and 275 corresponding targets in QHD were discovered through screening. 55 key target targets and 27 important signaling pathways were screened, such as the cancer pathway, P13K-AKT signaling pathway, PPAR signaling pathway, and other related signaling pathways. Conclusions. The present study revealed the material basis of QHD and discussed the pharmacological mechanism of QHD in fatty liver, thus providing a scientific basis for the clinical application and experimental research of QHD in the future.

scholarly journals Western Diet Causes Obesity-Induced Nonalcoholic Fatty Liver Disease Development by Differentially Compromising the Autophagic Response

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 995
Author(s):  
Ines C. M. Simoes ◽  
Agnieszka Karkucinska-Wieckowska ◽  
Justyna Janikiewicz ◽  
Sylwia Szymanska ◽  
Maciej Pronicki ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Coupling Efficiency ◽  
Acid Oxidation ◽  
Autophagic Flux ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Nonalcoholic Fatty Liver ◽  
Mitochondrial Fatty Acid

Nonalcoholic fatty liver disease (NAFLD) is characterized by the development of steatosis, which can ultimately compromise liver function. Mitochondria are key players in obesity-induced metabolic disorders; however, the distinct role of hypercaloric diet constituents in hepatic cellular oxidative stress and metabolism is unknown. Male mice were fed either a high-fat (HF) diet, a high-sucrose (HS) diet or a combined HF plus HS (HFHS) diet for 16 weeks. This study shows that hypercaloric diets caused steatosis; however, the HFHS diet induced severe fibrotic phenotype. At the mitochondrial level, lipidomic analysis showed an increased cardiolipin content for all tested diets. Despite this, no alterations were found in the coupling efficiency of oxidative phosphorylation and neither in mitochondrial fatty acid oxidation (FAO). Consistent with unchanged mitochondrial function, no alterations in mitochondrial-induced reactive oxygen species (ROS) and antioxidant capacity were found. In contrast, the HF and HS diets caused lipid peroxidation and provoked altered antioxidant enzyme levels/activities in liver tissue. Our work provides evidence that hepatic oxidative damage may be caused by augmented levels of peroxisomes and consequently higher peroxisomal FAO-induced ROS in the early NAFLD stage. Hepatic damage is also associated with autophagic flux impairment, which was demonstrated to be diet-type dependent. The HS diet induced a reduction in autophagosomal formation, while the HF diet reduced levels of cathepsins. The accumulation of damaged organelles could instigate hepatocyte injuries and NAFLD progression.

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