scholarly journals Integrating Network Pharmacology and RT-qPCR Analysis to Investigate the Mechanisms Underlying ZeXie Decoction-Mediated Treatment of Non-alcoholic Fatty Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiashuo Wu ◽  
Fangqing Zhang ◽  
Haonan Ruan ◽  
Xiaoyan Chang ◽  
Jingxun Wang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Network Pharmacology ◽  
Sprague Dawley ◽  
Alcoholic Fatty Liver ◽  
Pathway Network ◽  
Experimental Pharmacology ◽  
Mechanistic Basis ◽  
Alcoholic Fatty Liver Disease

ZeXie Decoction (ZXD) is a traditional Chinese medicine composed of Alisma orientalis (Sam.) Juzep. and Atractylodes macrocephala Koidz. ZXD has been widely used to treat non-alcoholic fatty liver disease (NAFLD). The mechanistic basis for the pharmacological activity of ZXD, however, remains poorly understood. In this study, we used a network pharmacology approach and investigated the association between ZXD and NAFLD. We identified the active ingredients of ZXD and screened the potential targets of these ingredients, after which a database of relevant NAFLD-related targets were constructed and several enrichment analyses were performed. Furthermore, the ethanol and aqueous extracts of ZXD were prepared and experimental pharmacology validation was conducted using RT-qPCR of the non-alcoholic fatty liver disease (NAFLD) model in Sprague-Dawley (SD) rats. As a result, a herb-compound-target-pathway network model was developed, and HMGCR, SREBP-2, MAPK1, and NF-κBp65 targets were validated. The gene expression results of these four targets were consistent with those of the network pharmacology prediction. Using an integration strategy, we revealed that ZXD could treat NAFLD by targeting HMGCR, SREBP-2, MAPK1, and NF-κBp65.

scholarly journals Network Pharmacology-Based Analysis on the Potential Biological Mechanisms of Sinisan Against Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoyi Wei ◽  
Weixin Hou ◽  
Jiajun Liang ◽  
Peng Fang ◽  
Bo Dou ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Shortest Path ◽  
Fatty Liver Disease ◽  
Path Length ◽  
Liver Steatosis ◽  
Network Pharmacology ◽  
Biological Mechanisms ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in China. Sinisan (SNS) is a traditional Chinese medicine formula that has been widely used in treating chronic liver diseases, including NAFLD. However, its underlying biological mechanisms are still unclear. In this study, we employed a network pharmacology approach consisting of overlapped terms- (genes or pathway terms-) based analysis, protein-protein interaction (PPI) network-based analysis, and PPI clusters identification. Unlike the previous network pharmacology study, we used the shortest path length-based network proximity algorithm to evaluate the efficacy of SNS against NAFLD. And we also used random walk with restart (RWR) algorithm and Community Cluster (Glay) algorithm to identify important targets and clusters. The screening results showed that the mean shortest path length between genes of SNS and NAFLD was significantly smaller than degree-matched random ones. Six PPI clusters were identified and ten hub targets were obtained, including STAT3, CTNNB1, MAPK1, MAPK3, AGT, NQO1, TOP2A, FDFT1, ALDH4A1, and KCNH2. The experimental study indicated that SNS reduced hyperlipidemia, liver steatosis, and inflammation. Most importantly, JAK2/STAT3 signal was inhibited by SNS treatment and was recognized as the most important signal considering the network pharmacology part. This study provides a systems perspective to study the relationship between Chinese medicines and diseases and helps to discover potential mechanisms by which SNS ameliorates NAFLD.

Network Pharmacology Research and Preliminary Verification of Gegen Qinlian Decoction for the Treatment of Non-Alcoholic Fatty Liver Disease

2020 ◽  
Vol 15 (5) ◽  
pp. 1934578X2092002
Author(s):  
Pengfei Hao ◽  
Yiyi Xiong ◽  
Hezhen Wu ◽  
Yanfang Yang
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Chemical Constituents ◽  
Network Pharmacology ◽  
Enzyme Linked Immunosorbent Assay ◽  
Alcoholic Fatty Liver ◽  
Compensation Mechanisms ◽  
Cellular Pathways ◽  
Alcoholic Fatty Liver Disease

Gegen Qinlian decoction (GQD) is a traditional Chinese medicine that is used to treat non-alcoholic fatty liver disease (NAFLD) in the clinic. The pharmacodynamics and cellular pathways governing the effects of GQD on NAFLD remain undefined. In this study, we investigated GQD pharmacology through assessment of its chemical constituents and evaluated and screened its components using drug likeness, pharmacokinetic characteristics (absorption, distribution, metabolism, excretion, and toxicity), and appropriate compensation mechanisms. We performed predictions of the active GQD ingredients based on reverse pharmacophore matching and compared multiple NAFLD-related genes to determine potential GQD targets. Molecular docking experiments of the active components were performed to reveal cellular targets. Annotation analysis of both target genes and related pathways were assessed through the DAVID database. Cytoscape software was used to construct a “component-target-path” network for the treatment of NAFLD by GQD. Through data analysis, 9 active GQD substances and 10 targets related to NAFLD encompassing 4 cellular pathways were identified. Data were verified through enzyme-linked immunosorbent assay and Western blot analysis. These findings provide new references for the network pharmacology of Chinese medicinal compounds and NAFLD treatment.

scholarly journals The Effect of Rat Strain, Diet Composition and Feeding Period on the Development of a Nutritional Model of Non-Alcoholic Fatty Liver Disease in Rats

2011 ◽  
pp. 317-328 ◽  
Author(s):  
O. KUČERA ◽  
T. GARNOL ◽  
H. LOTKOVÁ ◽  
P. STAŇKOVÁ ◽  
Y. MAZUROVÁ ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Wistar Rats ◽  
Male Rats ◽  
Standard Diet ◽  
Sprague Dawley ◽  
Alcoholic Fatty Liver ◽  
Sprague Dawley Rats ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver-related morbidity and mortality. The aim of this work was to establish and characterize a nutritional model of NAFLD in rats. Wistar or Sprague-Dawley male rats were fed ad libitum a standard diet (ST-1, 10 % kcal fat), a medium-fat gelled diet (MFGD, 35 % kcal fat) and a high-fat gelled diet (HFGD, 71 % kcal fat) for 3 or 6 weeks. We examined the serum biochemistry, the hepatic malondialdehyde, reduced glutathione (GSH) and cytokine concentration, the respiration of liver mitochondria, the expression of uncoupling protein-2 (UCP-2) mRNA in the liver and histopathological samples. Feeding with MFGD and HFGD in Wistar rats or HFGD in Sprague-Dawley rats induced small-droplet or mixed steatosis without focal inflammation or necrosis. Compared to the standard diet, there were no significant differences in serum biochemical parameters, except lower concentrations of triacylglycerols in HFGD and MFGD groups. Liver GSH was decreased in rats fed HFGD for 3 weeks in comparison with ST-1. Higher hepatic malondialdehyde was found in both strains of rats fed HFGD for 6 weeks and in Sprague-Dawley groups using MFGD or HFGD for 3 weeks vs. the standard diet. Expression of UCP-2 mRNA was increased in Wistar rats fed MFGD and HFGD for 6 weeks and in Sprague-Dawley rats using HFGD for 6 weeks compared to ST-1. The present study showed that male Wistar and Sprague-Dawley rats fed by HFGD developed comparable simple steatosis without signs of progression to non-alcoholic steatohepatitis under our experimental conditions.

scholarly journals Network Pharmacology Exploration Reveals Anti-Apoptosis as a Common Therapeutic Mechanism for Non-Alcoholic Fatty Liver Disease Treated with Blueberry Leaf Polyphenols

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4060
Author(s):  
Cai-Ren Wang ◽  
Hong-Wei Chen ◽  
Yan Li ◽  
Ming-Yue Zhou ◽  
Vincent Kam-Wai Wong ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Drug Targets ◽  
Cell Model ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Alcoholic Fatty Liver ◽  
Apoptosis Pathway ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease characterized by excessive fat accumulation in the liver. The aim of this study is to elucidate the multi-target mechanism of polyphenols in blueberry leaves (PBL) on NAFLD by network pharmacology and to validate its results via biological experiments. Twenty constituents in PBL were preliminarily determined by liquid chromatography-tandem mass spectrometry. Subsequently, 141 predicted drug targets and 1226 targets associated with NAFLD were retrieved from public databases, respectively. The herb-compound-target network and the target protein–protein interaction network (PPI) were established through Cytoscape software, and four compounds and 53 corresponding targets were identified. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed to explore the biological processes of the predicted genes. The results of cell experiments demonstrated that PBL could significantly improve the viability of the NAFLD cell model, and the protein expressions of caspase-3 and Bcl-2 were consistent with the expected mechanism of action of PBL. Those results systematically revealed that the multi-target mechanism of PBL against NAFLD was related to the apoptosis pathway, which could bring deeper reflections into the hepatoprotective effect of PBL.

scholarly journals Diet-Induced Rat Model of Gradual Development of Non-Alcoholic Fatty Liver Disease (NAFLD) with Lipopolysaccharides (LPS) Secretion

Diagnostics ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 205 ◽  
Author(s):  
Dominika Maciejewska ◽  
Agnieszka Łukomska ◽  
Karolina Dec ◽  
Karolina Skonieczna-Żydecka ◽  
Izabela Gutowska ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cholesterol Concentration ◽  
Control Group ◽  
Sprague Dawley ◽  
Alcoholic Fatty Liver ◽  
Gradual Development ◽  
Stage 1 ◽  
Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders in industrialized Western countries. The prevalence of the disease is estimated to range from 4% to 46% worldwide. The aim of study was to develop an animal model with gradual NAFLD development. Methods: Sprague-Dawley rats were fed a high-fat and high-cholesterol (HFHCh) diet. The rats from the study and control groups were sacrificed after 2, 4, 8, 12, 16, and 20 weeks of dietary exposure. Results: Analysis of biochemical parameters showed that after only two weeks, ALT and cholesterol concentration in serum were elevated. After 4 weeks, TNF-α and HOMA-IR were significantly higher compared to the control group. NAFLD progression started after 12 weeks of diet-weight gain and increased LPS secretions were noticed. During the experiment, rats induced steatosis (from stage 0/1 after 4 weeks to stage 2/3 after 20 weeks), inflammation (from stage 0/1 after 4 weeks to stage 1/2 after 20 weeks), and fibrosis (from stage 1 after 12 weeks to stage 2 after 20 weeks). Conclusion: We can assume that the presented model based on the HFHCh diet induced gradual development of NAFLD. We confirmed that the animal NAFLD model increases LPS secretions during disease progression.

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