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 Assessment of non-alcoholic fatty liver disease (NAFLD) severity with novel serum-based markers: A pilot study

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260313
Author(s):  
Atul Goyale ◽  
Anjly Jain ◽  
Colette Smith ◽  
Margarita Papatheodoridi ◽  
Marta Guerrero Misas ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Positive Likelihood Ratio ◽  
Public Health Issue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Roc Curve Analysis ◽  
Cross Sectional ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Background/Aims Non-alcoholic fatty liver disease (NAFLD) represents a significant public health issue. Identifying patients with simple steatosis from those with non-alcoholic steatohepatitis (NASH) is crucial since NASH is correlated with increased morbidity and mortality. Serum-based markers, including adipokines and cytokines, are important in the pathogenesis and progression of NAFLD. Here we assessed the usefulness of such markers in patients with NAFLD. Methods This prospective, cross-sectional study included 105 adult patients with varying severity of NAFLD. Twelve serum-based markers were measured by 3 biochip platforms and 2 enzyme-linked immunosorbent assay (ELISA) methods. We also developed a NAFLD individual fibrosis index (NIFI) using the serum-based markers mostly correlated with fibrosis severity. Results Sixty-one out of 105 patients were male (58.1%) with mean age was 53.5 years. Higher Interleukin-6 (IL-6) increased (p = 0.0321) and lower Matrix Metalloproteinase-9 (MMP-9) serum levels (p = 0.0031) were associated with higher fibrosis as measured by Fibroscan® in multivariable regression analysis. Using receiver-operating characteristic (ROC) curve analysis for the NIFI, area under the curve for predicting Fibroscan values ≥ 7.2 kPa was 0.77 (95%CI: 0.67, 0.88, p<0.001), with sensitivity of 89.3%, specificity of 57.9% and a positive likelihood ratio of 2.8. Conclusions Increasing fibrosis severity in NAFLD is associated with differential expression of IL-6 and MMP-9. NIFI could be valuable for the prediction of advanced NAFLD fibrosis and potentially help avoid unnecessary interventions such as liver biopsy in low-risk patients.

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.

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 CCL25 mediates inflammatory crosstalk between adipose and liver in non-alcoholic fatty liver disease

2021 ◽  
Author(s):  
Richard Parker ◽  
John Drake ◽  
Chris Weston ◽  
David H Adams
Keyword(s):  
Gene Expression ◽  
Liver Disease ◽  
Fatty Liver ◽  
Liver Tissue ◽  
Fatty Liver Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Leukocyte Trafficking ◽  
Alcoholic Fatty Liver ◽  
Hepatic Sinusoid ◽  
Alcoholic Fatty Liver Disease

Background and Aims: Obesity is closely associated with non-alcoholic fatty liver disease (NAFLD). We investigated expression of the CC-chemokine CCL25 in adipose tissue (AT) and its relation to hepatic inflammation. Methods: Primary human tissue was used for all experiments. CCL25 concentration in serum was measured with enzyme-linked immunosorbent assay (ELISA). Gene expression of CCL25 was measured with polymerase chain reaction. Protein expression was assessed with ELISA and immunohistochemistry. Leukocyte trafficking was investigated in a dynamic assay to model the hepatic sinusoid. Expression of CCR9 on liver-infiltrating leukocytes analysed with flow cytometry. Results: Circulating CCL25 was increased in obesity. Gene expression of CCL25 in AT was several-fold higher than in liver, although protein levels of CCL25 were comparable. Soluble CCL25 in flow media increased leukocyte trafficking across hepatic endothelium. Greater numbers of CCR9+ cells were seen in liver tissue from patients with NAFLD, where the greatest difference was in the number of CD14+CD16+ monocytes. Conclusions: CCL25 and its cognate receptor CCR9 mediate a novel pathway of inflammatory crosstalk between adipose and liver tissue in 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 Low serum Maresin-1 levels are associated with non-alcoholic fatty liver disease: a cross-sectional study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xia Fang ◽  
Hongya Wang ◽  
Ting Ye ◽  
Xiaolan Fu ◽  
Xiaozhen Tan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cross Sectional Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sectional Study ◽  
Cross Sectional ◽  
Alcoholic Fatty Liver ◽  
Maresin 1 ◽  
Alcoholic Fatty Liver Disease

Abstract Background Maresin-1 (MaR1) is an anti-inflammatory pro-resolving mediator and is considered a potential regulator of metabolic diseases. Non-alcoholic fatty liver disease (NAFLD) is a very common metabolic liver disease. However, little information is available on the relationship between MaR1 and NAFLD in humans. Therefore, the study explored the association between serum MaR1 levels and NAFLD. Methods A cross-sectional study was conducted in 240 Chinese people, including 116 non-NAFLD subjects and 124 NAFLD patients. Serum MaR1 levels were determined by enzyme-linked immunosorbent assay (ELISA). The association between MaR1 and NAFLD was assessed. Results Circulating MaR1 levels in NAFLD patients were markedly lower than those in non-NAFLD subjects (63.63 [59.87–73.93] vs 73.11 [65.12–84.50] pg/mL, P = 0.000). The percentages of patients with NAFLD gradually decreased with the increase of MaR1 quartiles (P < 0.001). Furthermore, serum MaR1 levels were positively associated with aspartate aminotransferase/alanine aminotransferase (AST/ALT), albumin, the albumin-globulin-ratio, and high-density lipoprotein cholesterol (HDL-C) (all P < 0.05) and negatively associated with body mass index (BMI), waist circumference, hip circumference, the waist-to-hip ratio, ALT, gamma-glutamyl transpeptidase (GGT), uric acid, triglyceride (TG), and fasting blood glucose (FBG) (all P < 0.05) after adjusting for sex and age. Binary logistic regression analysis revealed that serum MaR1 levels were significantly associated with NAFLD. Conclusions Circulating MaR1 levels were decreased in patients with NAFLD, and a negative correlation was identified between NAFLD and serum MaR1 concentrations. Decreased MaR1 might be involved in the development of NAFLD.

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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