Network Pharmacology, molecular docking technology integrated with pharmacodynamic study to reveal the potential targets of Schisandrol A in drug-induced liver injury by acetaminophen

2021 ◽  
pp. 105476
Author(s):  
Xiankuan Li ◽  
Jiaming Ge ◽  
Mengyuan Li ◽  
Sha Deng ◽  
Jiarong Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Liver Injury ◽  
Network Pharmacology ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Pharmacodynamic Study

Investigating the Mechanism of Action of Frankincense against Drug-Induced Liver Injury Using Network Pharmacology and Molecular Docking

2021 ◽  
Vol 18 ◽  
Author(s):  
Yu-cheng Liao ◽  
Jing-wen Wang ◽  
Qian Yang ◽  
Wen-jun Wanga ◽  
Chao Zhao ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Liver Injury ◽  
Mechanism Of Action ◽  
Target Genes ◽  
Network Pharmacology ◽  
Active Components ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Pathway Enrichment ◽  
Core Genes

Background: Frankincense has been used as a traditional medicine in many countries. It is an important herb with multiple targets and therapeutic effects including liver protection. However, its mechanism of action in drug-induced liver injury (DILI) remains unknown. Objective: The purpose of this work was to elucidate the active components, core genes, and molecular mechanism of frankincense in DILI through network pharmacology and molecular docking approaches. Method: The active components of frankincense and its target genes were obtained from the BATMAN-TCM database, and the DILI target genes were obtained from the GeneCards and DrugBank databases. Cytoscape was used to create the compound-shared gene target network. STRING and DAVID software were used to analyze key targets and pathway enrichment. Autodock Vina software was used for molecular docking. Results: Network analysis identified 16 compounds in frankincense and 103 target genes that are highly related to DILI. The core genes in the protein-protein interaction network are INS, IL6, TP53, TNF, SRC, PTGS2, IL1B, CAT, IL10, and IGF1. Furthermore, GO and KEGG pathway enrichment analyses indicated that the effect of frankincense on DILI is related to positive regulation of transcription from RNA polymerase II promoter and inflammatory response. Core pathways such as the HIF-1, TNF, FoxO, PI3K-Akt, and the sphingolipid signaling pathway are closely related to DILI. Conclusion: This study revealed the chemical constituents and pharmacological effects of frankincense and unveiled potential DILI healing targets. This study could provide insights for further development of drugs that specifically target DILI.

scholarly journals The Study on the Mechanism of Hugan Tablets in Treating Drug-Induced Liver Injury Induced by Atorvastatin

2021 ◽  
Vol 12 ◽  
Author(s):  
Shujing Lv ◽  
Honghong Yu ◽  
Xinyue Liu ◽  
Xiaoyan Gao
Keyword(s):  
Molecular Docking ◽  
Liver Injury ◽  
Protein Interactions ◽  
Enrichment Analysis ◽  
Lipid Lowering ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Drug Induced ◽  
Literature Research ◽  
Drug Induced Liver Injury

Atorvastatin is a widely used lipid-lowering drug in the clinic. Research shows that taking long-term atorvastatin has the risk of drug-induced liver injury (DILI) in most patients. Hugan tablets, a commonly used drug for liver disease, can effectively lower transaminase and protect the liver. However, the underlying mechanism of Hugan tablets alleviating atorvastatin-induced DILI remains unclear. To address this problem, comprehensive chemical profiling and network pharmacology methods were used in the study. First, the strategy of “compound−single herb−TCM prescription” was applied to characterize the ingredients of Hugan tablets. Then, active ingredients and potential targets of Hugan tablets in DILI treatment were screened using network pharmacology, molecular docking, and literature research. In the end, the mechanism of Hugan tablets in treating atorvastatin-induced DILI was elucidated. The results showed that Hugan tablets can effectively alleviate DILI induced by atorvastatin in model rats, and 71 compounds were characterized from Hugan tablets. Based on these compounds, 271 potential targets for the treatment of DILI were predicted, and 10 key targets were chosen by characterizing protein–protein interactions. Then, 30 potential active ingredients were screened through the molecular docking with these 10 key targets, and their biological activity was explained based on literature research. Finally, the major 19 active ingredients of Hugan tablets were discovered. In addition, further enrichment analysis of 271 targets indicated that the PI3K-Akt, TNF, HIF-1, Rap1, and FoxO signaling pathways may be the primary pathways regulated by Hugan tablets in treating DILI. This study proved that Hugan tablets could alleviate atorvastatin-induced DILI through multiple components, targets, and pathways.

scholarly journals Systematic Elucidation of the Potential Mechanism of Erzhi Pill against Drug-Induced Liver Injury via Network Pharmacology Approach

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Shao-jie Huang ◽  
Fei Mu ◽  
Fei Li ◽  
Wen-jun Wang ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Bioactive Compounds ◽  
Network Pharmacology ◽  
Potential Mechanism ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Research Orientation ◽  
Novel Approach ◽  
Apoptosis Process ◽  
Pathway Analyses

Objective. The purpose of this work was to investigate the bioactive compounds, core genes, and pharmacological mechanisms and to provide a further research orientation of Erzhi pill (EZP) on drug-induced liver injury (DILI). Methods. At first, we collected information of bioactive compounds of EZP from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and previous studies. And then, the targets related to bioactive compounds and DILI were obtained from 4 public databases. At last, Cytoscape was used to establish a visual network. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and network analysis were performed to investigate potential mechanism of EZP against DILI. Results. A total of 23 bioactive compounds and 89 major proteins of EZP were screened out as potential players against DILI. Association for bioactive compounds, core targets, and related pathways was analyzed, implying that core targets related to these pathways are ALB, AKT1, MAPK1, EGFR, SRC, MAPK8, IGF1, CASP3, HSP90AA1, and MMP9, and potential mechanisms of EZP acting on DILI are closely related to negative regulation of apoptosis process, improvement of lipid metabolism, and positive regulation of liver regeneration process. Conclusion. This study demonstrated the multicompound, multitarget, and multichannel characteristics of EZP, which provided a novel approach for further research the mechanism of EZP in the treatment of DILI.

Leberschaden unter oraler Antikoagulation, Statin- und ACE-Hemmertherapie

Praxis ◽  
2010 ◽  
Vol 99 (21) ◽  
pp. 1259-1265 ◽  
Author(s):  
Bruggisser ◽  
Terraciano ◽  
Rätz Bravo ◽  
Haschke
Keyword(s):  
Liver Injury ◽  
Wird Eine ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Ein 71-jähriger Patient stellt sich mit Epistaxis und ikterischen Skleren auf der Notfallstation vor. Der Patient steht unter einer Therapie mit Phenprocoumon, Atorvastatin und Perindopril. Anamnestisch besteht ein langjähriger Alkoholabusus. Laborchemisch werden massiv erhöhte Leberwerte (ALAT, Bilirubin) gesehen. Der INR ist unter oraler Antikoagulation und bei akuter Leberinsuffizienz >12. Die weiterführenden Abklärungen schliessen eine Virushepatitis und eine Autoimmunhepatitis aus. Nachdem eine Leberbiopsie durchgeführt werden kann, wird eine medikamentös-toxische Hepatitis, ausgelöst durch die Komedikation von Atorvastatin, Phenprocoumon und Perindopril bei durch Alkohol bereits vorgeschädigter Leber diagnostiziert. Epidemiologie, Pathophysiologie und Klink der medikamentös induzierten Leberschäden (drug induced liver injury, DILI), speziell von Coumarinen, Statinen und ACE-Hemmern werden im Anschluss an den Fallbericht diskutiert.

Drug-induced liver injury network (DILIN)

Hepatology ◽  
2004 ◽  
Vol 40 (4) ◽  
pp. 773-773 ◽  
Author(s):  
Jay H. Hoofnagle
Keyword(s):  
Liver Injury ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Drug induced liver injury associated with Flupirtine in 6 cases

2011 ◽  
Vol 49 (08) ◽  
Author(s):  
C Agne ◽  
K Rifai ◽  
HH Kreipe ◽  
MP Manns ◽  
F Puls
Keyword(s):  
Liver Injury ◽  
Drug Induced ◽  
Drug Induced Liver Injury
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