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 Non-alcoholic fatty liver disease, obesity and other illnesses

2008 ◽  
Vol 31 (5) ◽  
pp. 290 ◽  
Author(s):  
Giovanni Tarantino
Keyword(s):  
Liver Disease ◽  
General Population ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Drug Targets ◽  
Common Mechanism ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The estimated prevalence of NonAlcoholic Fatty Liver Disease in the general population in western countries is about 30%, but it is higher among obese and diabetic people. It is likely that more sophisticated approaches are required to understand its pathogenesis and to develop drug targets. In the meantime, the range of associations between NAFLD and other illnesses broadens. Although association does not mean causation, the link between some diseases and NAFLD suggests a common mechanism.

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 Strategies of Cell Signaling and Critical Focus on Etiology of Hepatocellular Carcinoma

2021 ◽  
Vol 12 (4) ◽  
pp. 5187-5198
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Signaling Pathways ◽  
Fatty Liver Disease ◽  
Drug Targets ◽  
Incidence Rates ◽  
Therapeutic Drug ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Hepatocellular carcinoma is an atypical biological cell process that is frequently identified at an advanced stage, with no promising therapeutic options available. Hepatocarcinogenesis is connected to a range of cellular signaling pathways, notably Wnt-β-catenin (canonical Wnt pathway), nuclear factor-B, and YAP-HIPPO (Yes-associated protein Salvador-Warts-Hippo pathway); each of these is considered a potential pharmacological candidate. Inflammation in the liver for a long time and damage play a big role in the incidence and development of HCC. HCC incidence rates go up by the many variables such as sex, age, ethnicity, and demographics are all factors to consider, and the leading causes of infection by the chronic or hepatitis B virus (HBV), hepatitis C virus (HCV), nutrient pollutants, ecological poisons, tobacco smoldering, and genetic disorders, which are all carcinogens. In this review, we expanded on our existing empathetic of the signaling pathways involved in the development and genesis of HCC. We also encapsulated the etiology of HCC, with a focus on HCC triggered by non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD). In this review, we forecasted potential therapeutic drug targets.

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