xploring Mechanism of Gardenia jasminoides against Non-Alcoholic Fatty Liver Disease by Network Pharmacology and Molecular Docking Method

2022 ◽  
Vol 11 (01) ◽  
pp. 51-63
Author(s):  
露 孙
Keyword(s):  
Molecular Docking ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Network Pharmacology ◽  
Alcoholic Fatty Liver ◽  
Gardenia Jasminoides ◽  
Docking Method ◽  
Alcoholic Fatty Liver Disease ◽  
Molecular Docking Method

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 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 Exploring the Mechanism of Danggui Shaoyao San in the treatment of Non-alcoholic Fatty Liver Disease: A Study based on Network Pharmacology and Molecular Docking

2022 ◽  
Author(s):  
luyun xia ◽  
Zheng Luo ◽  
Haiyan Zhu ◽  
Yu-qin Tang ◽  
Lili Huang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Liver Disease ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Fatty Liver ◽  
Signaling Pathway ◽  
Fatty Liver Disease ◽  
Active Ingredients ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver disease in the world, has yet to identify a particular medicine for treatment. Danggui Shaoyao San (DSS), a traditional Chinese medicine formula, has steadily been employed to treat NAFLD in recent years. Methods The active ingredients of the DSS were screened from the Traditional Chinese Medicine Systems Pharmacology (TCMSP), and the candidate targets of the ingredients were collected through the PharmMapper platform. NAFLD-related targets were acquired from NCBI, DisGeNet, Genecards databases. Venn diagram was used to identify possible DSS drug strategies in the treatment of NAFLD. Active ingredients - potential therapeutic targets network constructed in Cytoscape. The STRING database provides PPI networks. Metascape was used to evaluate targets using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, molecular docking simulations were performed using Pymol 2.4.0, AutoDuck Tools 1.5.6 and LigPlot 2.2.4 software to assess the affinity of key ingredients and targets. Results 51 compounds were screened in the DSS, including paeoniflorin, poric acid A and poric acid B. There are a total of 38 cross-targets between herbs and NAFLD. PPI network analysis identified AKT1, ALB, PPARG, and CASP3 as priority targets. GO analysis focused on vesicle lumen, nutrition levels, and nitrous-oxide synthase regulator activity. DSS may have therapeutic benefits via the pathways in cancer,foxo signaling pathway,IL-17 signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway according to KEGG analysis. Sitosterol and β- sitosterol were proven to be true promising compounds with excellent affinity in the final molecular docking. Conclusions DSS entails a number of components, targets, and routes, and it provides novel therapy and preventative alternatives for NAFLD.

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 Mechanism of Paeoniae Radix Alba in the Treatment of Non-alcoholic Fatty Liver Disease Based on Sequential Metabolites Identification Approach, Network Pharmacology, and Binding Affinity Measurement

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhiqiang Luo ◽  
Yang Liu ◽  
Xing Han ◽  
Wenning Yang ◽  
Guopeng Wang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Liver Disease ◽  
Fatty Liver Disease ◽  
Network Pharmacology ◽  
Alcoholic Fatty Liver ◽  
Blood Samples ◽  
Integrated Strategy ◽  
Identification Approach ◽  
Paeoniae Radix ◽  
Alcoholic Fatty Liver Disease

Screening functional food ingredients (FFI) from medicinal and edible plants (MEP) has still remained a great challenge due to the complexity of MEP and its obscure function mechanisms. Herein, an integrated strategy based on sequential metabolites identification approach, network pharmacology, molecular docking, and surface plasmon resonance (SPR) analysis was proposed for quickly identifying the active constituents in MEP. First, the sequential biotransformation process of MEP, including intestinal absorption and metabolism, and hepatic metabolism, was investigated by oral gavage, and intestinal perfusion with venous sampling method. Then the blood samples were analyzed by UPLC-Q Exactive Orbitrap HRMS. Second, the network pharmacology approach was used to explore the potential targets and possible mechanisms of the in vivo metabolites of MEP. Third, molecular docking and SPR approaches were used to verify the specific interactions between protein targets and representative ingredients. The proposed integrated strategy was successfully used to explore the heptoprotective components and the underlying molecular mechanism of Paeoniae Radix Alba (PRA). A total of 44 compounds were identified in blood samples, including 17 porotypes and 27 metabolites. The associated metabolic pathways were oxidation, methylation, sulfation, and glucuronidation. After further screening, 31 bioactive candidates and 377 related targets were obtained. In addition, the bioactive components contained in PRA may have therapeutic potentials for non-alcoholic fatty liver disease (NAFLD). The above results demonstrated the proposed strategy may provide a feasible tool for screening FFI and elaborating the complex function mechanisms of MEP.

Vitamin D levels are not associated with non-alcoholic fatty liver disease severity in a Brazilian population

2020 ◽  
pp. 1-8
Author(s):  
Jeniffer Danielle M. Dutra ◽  
Quelson Coelho Lisboa ◽  
Silvia Marinho Ferolla ◽  
Carolina Martinelli M. L. Carvalho ◽  
Camila Costa M. Mendes ◽  
...  
Keyword(s):  
Vitamin D ◽  
Liver Disease ◽  
Fatty Liver ◽  
Disease Severity ◽  
Fatty Liver Disease ◽  
Hypovitaminosis D ◽  
Alcoholic Fatty Liver ◽  
Vitamin D Levels ◽  
The Mean ◽  
Alcoholic Fatty Liver Disease

Abstract. Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were < 30 ng/mL in 78% of the patients, and < 20 ng/mL in 35%. The mean vitamin D level was 24.3 ± 6.8 ng/mL. The comparison between the clinical, biochemical and histological characteristics of the patients according to the levels of vitamin D showed no significant difference. Most patients with NAFLD had hypovitaminosis D, but low vitamin D levels were not related to disease severity and the presence of comorbidities.

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