scholarly journals Identify Key Active Ingredients and Molecular Mechanisms of Jiangzhi Decoction on Non-alcoholic Fatty Liver Disease by Network Pharmacology Analysis

2020 ◽  
Author(s):  
Lei Wang ◽  
Yin Zhi ◽  
Ying Ye ◽  
Miao Zhang ◽  
Xing Ma ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chinese Medicine ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Active Ingredients ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Background: Jiangzhi Decoction (JZD), a traditional herb mixture, has shown significant clinical efficacy against non-alcoholic fatty liver disease (NAFLD). However, its multicomponent and multitarget characteristics bring difficulty in deciphering its pharmacological mechanisms. Our study aimed to identify the key active ingredients and core molecular mechanisms of JZD against NAFLD. Methods: The active ingredients were searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Traditional Chinese Medicine Integrated Database (TCMID). The targets of those ingredients were identified using ChemMapper database based on 3D-structure similarity. NAFLD-related genes were searched from DisGeNET database and Gene Expression Omnibus (GEO) database. Then we obtained candidate targets of JZD against NAFLD by overlapping the active ingredient targets and NAFLD-related genes. We performed protein-protein interaction (PPI) analysis, functional enrichment analysis and constructed pathway networks of “herbs-active ingredients-candidate targets”, and identified the key active ingredients and core molecular mechanisms in the network. Results: We found 147 active ingredients in JZD, 1285 targets of active ingredients, 401 NAFLD-related genes, and 59 overlapped candidate targets of JZD against NAFLD. 22 core targets were obtained by PPI analysis. Finally, nuclear receptor transcription and lipid metabolism regulation were found as the core molecular mechanisms of JZD against NAFLD by functional enrichment analysis, and emodin, emodin anthrone, hyperin, questin, rhein, etc. were speculated as the key active ingredients of JZD. Conclusion: Our study will provide the scientific evidences of the clinical efficacy of JZD against NAFLD.

scholarly journals Identify Molecular Mechanisms of Jiangzhi Decoction on Nonalcoholic Fatty Liver Disease by Network Pharmacology Analysis and Experimental Validation

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Lei Wang ◽  
Yin Zhi ◽  
Ying Ye ◽  
Miao Zhang ◽  
Xing Ma ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Active Ingredients ◽  
Nonalcoholic Fatty Liver ◽  
The Core

Background. Jiangzhi Decoction (JZD), a traditional herb mixture, has shown significant clinical efficacy against nonalcoholic fatty liver disease (NAFLD). However, its multicomponent and multitarget characteristics bring difficulty in deciphering its pharmacological mechanisms. Our study is aimed at identifying the core molecular mechanisms of JZD against NAFLD. Methods. The active ingredients were searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Traditional Chinese Medicine Integrated Database (TCMID). The targets of those ingredients were identified using ChemMapper database based on 3D structure similarity. NAFLD-related genes were searched from DisGeNET database and Gene Expression Omnibus (GEO) database. Then, we performed protein-protein interaction (PPI) analysis, functional enrichment analysis, and constructed pathway networks of “herbs-active ingredients-candidate targets” and identified the core molecular mechanisms and key active ingredients in the network. Also, molecular docking was carried out to predict the ligands of candidate targets using SwissDock. Finally, the human hepatic L02 cell line was used to establish the NAFLD model in vitro. The effect and key molecules were validated by Oil Red O staining, biochemical assays, and quantitative real-time PCR (qRT-PCR). Results. We found 147 active ingredients in JZD, 1285 targets of active ingredients, 401 NAFLD-related genes, and 59 overlapped candidate targets of JZD against NAFLD. 22 core targets were obtained by PPI analysis. Finally, nuclear receptor transcription and lipid metabolism regulation were found as the core molecular mechanisms of JZD against NAFLD by functional enrichment analysis. The candidate targets PPARα and LXRα were both docked with hyperin as the most favorable interaction, and HNF4α was docked with linolenic acid ethyl ester. According to in vitro experiments, it was found that JZD had an inhibitory effect on lipid accumulation and regulatory effects on cholesterol and triglycerides. Compared with OA group, the mRNA expression levels of PPARα and HNF4α were significantly upregulated in JZD group ( P < 0.05 ), and LXRα was significantly downregulated ( P < 0.001 ). Conclusion. JZD might alleviate hepatocyte steatosis by regulating some key molecules related to nuclear receptor transcription and lipid metabolism, such as PPARα, LXRα, and HNF4α. Our study will provide the scientific evidences of the clinical efficacy of JZD against NAFLD.

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.

Molecular mechanisms of non-alcoholic fatty liver disease development

2021 ◽  
Vol 24 (4) ◽  
pp. 120
Author(s):  
T.S. Sall ◽  
E.S. Shcherbakova ◽  
S.I. Sitkin ◽  
T.Ya. Vakhitov ◽  
I.G. Bakulin ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Disease Development ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Traditional Chinese medicine Lingguizhugan decoction treating non-alcoholic fatty liver disease with spleen-yang deficiency pattern: Study protocol for a multicenter randomized controlled trial

2020 ◽  
Author(s):  
Jing-juan Xu ◽  
Rui-rui Wang ◽  
Sheng-fu You ◽  
Lei Zhang ◽  
Pei-yong Zheng ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Liver Function ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Clinical Symptoms ◽  
Efficacy And Safety ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a metabolic stress liver injury induced by excessive fat accumulation in liver, which is closely related to insulin resistance (IR). Traditional Chinese medicine (TCM) has showed good curative effects and unique advantages in the prevention and treatment of NADLD, particularly in improving IR, liver function and clinical symptoms. This study will examine the efficacy and safety of Lingguizhugan decoction (LGZG) in the treatment of non-alcoholic fatty liver disease with spleen-yang deficiency pattern, and assess the optimal dosage. Methods/design This study is a three-arm, dose-optimization, randomized, double-blinded, placebo-controlled clinical trial. A total of 243 NAFLD patients will be recruited and randomly assigned to standard dose Lingguizhugan decoction (SLGD) group, low dose Lingguizhugan decoction (LLGD) group, or the control group. The clinical indicator will be assessed during the 12-week intervention and follow-up 4 weeks. The primary outcome is the percentage of patients whose the decline of HOMA-IR reaches one standard unit. Secondary outcomes include body weight, body mass index, liver function, blood lipid metabolism, blood glucose metabolism, liver-kidney echo ratio, quantitative rating of clinical symptoms and signs, collecting sample(s) from participants, the medical outcomes study(MOS) item short from health survey(SF-36), Self-rating Depressive Scale(SAS), and Self-rating Anxiety Scale(SDS). Discussion This study will provide initial evidence regarding the efficacy and safety of LGZG in the treatment of NAFLD with spleen-yang deficiency pattern, meanwhile establish the demonstration technique, and promote its application in community healthcare center. In addition, potential mechanism will be explored based on research of oral and gut microbiota.

scholarly journals Hepatokines and Non-Alcoholic Fatty Liver Disease: Linking Liver Pathophysiology to Metabolism

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1903
Author(s):  
Tae Hyun Kim ◽  
Dong-Gyun Hong ◽  
Yoon Mee Yang
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Therapeutic Targets ◽  
Signaling Crosstalk ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The liver plays a key role in maintaining energy homeostasis by sensing and responding to changes in nutrient status under various metabolic conditions. Recently highlighted as a major endocrine organ, the contribution of the liver to systemic glucose and lipid metabolism is primarily attributed to signaling crosstalk between multiple organs via hepatic hormones, cytokines, and hepatokines. Hepatokines are hormone-like proteins secreted by hepatocytes, and a number of these have been associated with extra-hepatic metabolic regulation. Mounting evidence has revealed that the secretory profiles of hepatokines are significantly altered in non-alcoholic fatty liver disease (NAFLD), the most common hepatic manifestation, which frequently precedes other metabolic disorders, including insulin resistance and type 2 diabetes. Therefore, deciphering the mechanism of hepatokine-mediated inter-organ communication is essential for understanding the complex metabolic network between tissues, as well as for the identification of novel diagnostic and/or therapeutic targets in metabolic disease. In this review, we describe the hepatokine-driven inter-organ crosstalk in the context of liver pathophysiology, with a particular focus on NAFLD progression. Moreover, we summarize key hepatokines and their molecular mechanisms of metabolic control in non-hepatic tissues, discussing their potential as novel biomarkers and therapeutic targets in the treatment of metabolic diseases.

scholarly journals Hepatic Lipidomics and Molecular Imaging in a Murine Non-Alcoholic Fatty Liver Disease Model: Insights into Molecular Mechanisms

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1275
Author(s):  
Ricardo Rodríguez-Calvo ◽  
Sara Samino ◽  
Josefa Girona ◽  
Neus Martínez-Micaelo ◽  
Pere Ràfols ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Adipose Tissue ◽  
Liver Disease ◽  
Molecular Imaging ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Tissue Imaging ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

An imbalance between hepatic fatty acid uptake and removal results in ectopic fat accumulation, which leads to non-alcoholic fatty liver disease (NAFLD). The amount and type of accumulated triglycerides seem to play roles in NAFLD progression; however, a complete understanding of how triglycerides contribute to NAFLD evolution is lacking. Our aim was to evaluate triglyceride accumulation in NAFLD in a murine model and its associations with molecular mechanisms involved in liver damage and adipose tissue-liver cross talk by employing lipidomic and molecular imaging techniques. C57BL/6J mice fed a high-fat diet (HFD) for 12 weeks were used as a NAFLD model. Standard-diet (STD)-fed animals were used as controls. Standard liver pathology was assessed using conventional techniques. The liver lipidome was analyzed by liquid chromatography–mass spectrometry (LC–MS) and laser desorption/ionization–mass spectrometry (LDI–MS) tissue imaging. Liver triglycerides were identified by MS/MS. The transcriptome of genes involved in intracellular lipid metabolism and inflammation was assessed by RT-PCR. Plasma leptin, resistin, adiponectin, and FABP4 levels were determined using commercial kits. HFD-fed mice displayed increased liver lipid content. LC–MS analyses identified 14 triglyceride types that were upregulated in livers from HFD-fed animals. Among these 14 types, 10 were identified in liver cross sections by LDI–MS tissue imaging. The accumulation of these triglycerides was associated with the upregulation of lipogenesis and inflammatory genes and the downregulation of β-oxidation genes. Interestingly, the levels of plasma FABP4, but not of other adipokines, were positively associated with 8 of these triglycerides in HFD-fed mice but not in STD-fed mice. Our findings suggest a putative role of FABP4 in the liver-adipose tissue cross talk in NAFLD.

Integrated Bioinformatics Analysis Reveals Potential Mechanisms Associated with Intestinal Flora Intervention in Non-alcoholic Fatty Liver Disease

2020 ◽  
Author(s):  
Yingying Liu ◽  
Xinkui Liu ◽  
Wei Zhou ◽  
Jingyuan Zhang ◽  
Siyu Guo ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Signaling Pathway ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Intestinal Flora ◽  
Global Public Health ◽  
Alcoholic Fatty Liver ◽  
Key Genes ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease that imposes a huge economic burden on global public health. And the gut-liver axis theory supports the therapeutic role of intestinal flora in the development and progression of NAFLD. To this end, we designed bioinformatics study on the relationship between intestinal flora disorder and NAFLD, so as to explore the molecular mechanism of intestinal flora interfering with NAFLD. Methods Differentially expressed genes for NAFLD were obtained from GEO database. And the disease genes for NAFLD and intestinal flora disorder were obtained from the disease databases. Using string 11.0 database to establish protein-protein interaction network relationship and cytoscape 3.7.2 software visualization. Cytoscape plug-in MCODE and cytoHubba were used to screen the potential genes of intestinal flora disorder and NAFLD, so as to obtain potential targets for intestinal flora to interfere in the occurrence and process of NAFLD. Enrichment analysis of potential targets was carried out using R 4.0.2 software. Results The results showed that PTGS2, SPINK1 and C5AR1 may be the key genes for intestinal flora to interfere with NAFLD. CCL2, IL6, IL1B and FOS may be key genes for the development and progression of NAFLD. The gene function is mainly reflected in basic biological processes, including the regulation of metabolic process, epithelial development and immune influence. The pathway is mainly related to signal transduction, immune regulation and physiological metabolism. The TNF signaling pathway, AGE-RAGE signaling pathway in the diabetic activity, and NF-Kappa B signaling pathways are important pathways for intestinal flora to interfere with NAFLD. Conclusion According to the analysis results, there is a certain correlation between intestinal flora disorder and NAFLD. It is speculated that the mechanism by which intestinal flora may interfere with the occurrence and development of NAFLD is mainly related to inflammatory response and insulin resistance. Nevertheless, further research is needed to explore the specific molecular mechanisms.

Deciphering non-alcoholic fatty liver disease through metabolomics

2014 ◽  
Vol 42 (5) ◽  
pp. 1447-1452 ◽  
Author(s):  
Ainara Cano ◽  
Cristina Alonso
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Membrane Integrity ◽  
Alcoholic Fatty Liver ◽  
Metabolic Fluxes ◽  
Starting Point ◽  
Initial Symptoms ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders in industrialized countries. NAFLD develops in the absence of alcohol abuse and encompasses a wide spectrum of disorders ranging from benign fatty liver to non-alcoholic steatohepatitis (NASH). NASH often leads to fibrosis, cirrhosis and, finally, hepatocellular carcinoma (HCC). Therefore the earlier NAFLD is diagnosed, the better the patient's outlook. A tightly connected basic and applied research is essential to find the molecular mechanisms that accompany illness and to translate them into the clinic. From the simple starting point for triacylglycerol (TG) accumulation in the liver to the more complex implications of phospholipids in membrane biophysics, the influence of lipids may be the clue to understand NAFLD pathophysiology. Nowadays, it is achievable to diagnose non-invasively the initial symptoms to stop, revert or even prevent disease development. In this context, merging metabolomics with other techniques and the interpretation of the huge information obtained resembles the ‘Rosetta stone’ to decipher the pathological metabolic fluxes that must be targeted to find a cure. In the present review, we have tackled the application of metabolomics to find out the metabolic fluxes that underlie membrane integrity in NAFLD.

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