Management of Liver Disease in Thalassemia: Main Drug Targets for a Correct Therapy

AbstractIn the past decade, G protein-coupled receptors have emerged as drug targets, and their physiological and pathological effects have been extensively studied. Among these receptors, GPR119 is expressed in multiple organs, including the liver. It can be activated by a variety of endogenous and exogenous ligands. After GPR119 is activated, the cell secretes a variety of incretins, including glucagon-like peptide-1 and glucagon-like peptide-2, which may attenuate the metabolic dysfunction associated with fatty liver disease, including improving glucose and lipid metabolism, inhibiting inflammation, reducing appetite, and regulating the intestinal microbial system. GPR119 has been a potential therapeutic target for diabetes mellitus type 2 for many years, but its role in metabolic dysfunction associated fatty liver disease deserves further attention. In this review, we discuss relevant research and current progress in the physiology and pharmacology of the GPR119/incretin axis and speculate on the potential therapeutic role of this axis in metabolic dysfunction associated with fatty liver disease, which provides guidance for transforming experimental research into clinical applications.

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The Role of the Sodium-taurocholate Co-transporting Polypeptide (NTCP) and Bile Salt Export Pump (BSEP) in Related Liver Disease

Current Drug Metabolism ◽

10.2174/1389200220666190426152830 ◽

2019 ◽

Vol 20 (5) ◽

pp. 377-389 ◽

Cited By ~ 3

Author(s):

Xiaoyang Lu ◽

Lin Liu ◽

Wenya Shan ◽

Limin Kong ◽

Na Chen ◽

...

Keyword(s):

Liver Disease ◽

Structure Function ◽

Bile Salt ◽

Drug Targets ◽

Enterohepatic Circulation ◽

Sodium Taurocholate ◽

Bile Salt Export Pump ◽

Bile Acid Transporters ◽

Function Relationship ◽

Related Liver Disease

Background:Sodium Taurocholate Co-transporting Polypeptide (NTCP) and Bile Salt Export Pump (BSEP) play significant roles as membrane transporters because of their presence in the enterohepatic circulation of bile salts. They have emerged as promising drug targets in related liver disease.Methods:We reviewed the literature published over the last 20 years with a focus on NTCP and BSEP.Results:This review summarizes the current perception about structure, function, genetic variation, and regulation of NTCP and BSEP, highlights the effects of their defects in some hepatic disorders, and discusses the application prospect of new transcriptional activators in liver diseases.Conclusion:NTCP and BSEP are important proteins for transportation and homeostasis maintenance of bile acids. Further research is needed to develop new models for determining the structure-function relationship of bile acid transporters and screening for substrates and inhibitors, as well as to gain more information about the regulatory genetic mechanisms involved in the processes of liver injury.

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New drug targets for alcoholic liver disease

Hepatology International ◽

10.1007/s12072-014-9516-x ◽

2014 ◽

Vol 8 (S2) ◽

pp. 475-480 ◽

Cited By ~ 5

Author(s):

Mingjiang Xu ◽

Binxia Chang ◽

Stephanie Mathews ◽

Bin Gao

Keyword(s):

Liver Disease ◽

Alcoholic Liver Disease ◽

Drug Targets ◽

New Drug

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Non-alcoholic fatty liver disease, obesity and other illnesses

Clinical & Investigative Medicine ◽

10.25011/cim.v31i5.4876 ◽

2008 ◽

Vol 31 (5) ◽

pp. 290 ◽

Cited By ~ 6

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.

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

Nutrients ◽

10.3390/nu13114060 ◽

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.

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

Biointerface Research in Applied Chemistry ◽

10.33263/briac124.51875198 ◽

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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Prioritizing drug targets for non-alcoholic fatty liver disease based on comorbidity network analysis

Zeitschrift für Gastroenterologie ◽

10.1055/s-0036-1586961 ◽

2016 ◽

Vol 54 (08) ◽

Author(s):

TP Nguyen ◽

T Sauter ◽

L Caberlotto ◽

F Lammert ◽

JG Schneider

Keyword(s):

Liver Disease ◽

Network Analysis ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Drug Targets ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

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Alcoholic and Non-Alcoholic Liver Diseases: Promising Molecular Drug Targets and their Clinical Development

Current Drug Discovery Technologies ◽

10.2174/1570163817666200121143959 ◽

2020 ◽

Vol 17 ◽

Author(s):

Komal Thapa ◽

Ajmer Singh Grewal ◽

Neha Kanojia ◽

Lata Rani ◽

Neelam Sharma ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Liver Diseases ◽

Drug Targets ◽

Clinical Investigation ◽

Treatment Options ◽

Clinical Status ◽

Lipid Lowering ◽

Alcoholic Fatty Liver ◽

Alcoholic Liver Diseases

Alcoholic and non-alcoholic fatty liver diseases have become a serious concern whole over the world. Both these liver diseases have an identical pathology, starting from simple steatosis to cirrhosis and ultimately to hepatocellular carcinoma. Treatment options for alcoholic liver disease (ALD) are still same as it was 50 years ago which includes corticosteroids, pentoxifylline, antioxidants, nutritional support and abstinence; and for non-alcoholic fatty liver disease (NAFLD) weight loss, insulin sensitizers, lipid lowering agents and anti-oxidants are the only treatment options. Despite of broad research in understanding the disease pathophysiology, limited treatments are available for clinical use. Some therapeutic strategies based on targeting a specific molecule have been developed to lessen the consequences of disease and are under clinical investigation. Therefore, focus on multiple molecular targets will help to develop an efficient therapeutic strategy. This review comprises of brief overview of pathogenesis of ALD and NAFLD; recent molecular drug targets explored for ALD and NAFLD that may prove to be effective for multiple therapeutic regimens and also clinical status of these promising drug targets for liver diseases.

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