Shuai Wang , Yu Sun , Chunmei Zhang , Bohao Chen , Mei Zhong , Ruili Du , Yuhang Zhou , Guangdong Tong , Lidan Luo
{"title":"网络药理学、分子对接和实验验证揭示了益肝煎治疗急性肝衰竭的机理。","authors":"Shuai Wang , Yu Sun , Chunmei Zhang , Bohao Chen , Mei Zhong , Ruili Du , Yuhang Zhou , Guangdong Tong , Lidan Luo","doi":"10.1016/j.eujim.2023.102326","DOIUrl":null,"url":null,"abstract":"<div><p><em>Introduction</em>: The potential targets and action mechanism of Yiguanjian (YGJ) decoction in treating acute liver failure (ALF) were determined using network pharmacology, molecular docking and cell experiments.</p><p><em>Methods</em>: The Pharmacology of Traditional Chinese Medicine Systems (TCMSP) and BATMAN-TCM databases were used to find YGJ decoction targets. The Genecard database was employed to predict targets associated with ALF. Cytascape software was utilised to visualise and select common targets along with establishing a protein–protein interaction (PPI) network. Core targets were screened and putative function was assessed via gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyzes. Molecular docking was performed using AutodockTools, PyMoL and Discovery Studio software to verify the correlation between the YGJ decoction and selected targets. MTT assay was conducted to determine the effect of the YGJ decoction on the viability of Huh-7 human hepatoma cells. The effects of the YGJ decoction on the expression of putative targets in Huh-7 cells were determined via western blot and quantitative real-time polymerase chain reaction analyzes.</p><p><em>Results</em>: Overall, 9153 YGJ decoction and 576 ALF-related targets were obtained, and 469 YGJ decoction and ALF cross targets were obtained. Of these, 20 key targets, including AKT1, estrogen receptor 1 (ESR1), catalase (CAT), interleukin-1β (IL-1β) and discs large homolog 4 (DLG4), were selected from the PPI network. GO function enrichment analysis revealed that these targets were primarily associated with regulating system processes, cell body, oxidoreductase activity and other processes. An enrichment analysis using the KEGG pathway database revealed that the treatment of ALF using the YGJ decoction was primarily associated with the AGE-RAGE, cGMP-PKG and HIF-1 signalling pathways. Molecular docking indicated that quercetin, stigmasterol and β- sitosterol as well as AKT1, ESR1, CAT, IL-1β and DLG4 exhibited good binding affinity. <em>In vitro</em> experiments revealed that the YGJ decoction significantly reversed lipopolysaccharide (LPS)-induced apoptosis (<em>P</em> < 0.01), inhibited LPS-induced increase in IL-1β and ESR1 levels and upregulated LPS-induced decrease in AKT1, CAT and DLG4 levels (<em>P</em> < 0.05).</p><p><em>Conclusions</em>: The YGJ decoction alleviates ALF by regulating multiple targets and its action mechanism may be associated with ameliorating oxidative stress and inflammation.</p></div>","PeriodicalId":11932,"journal":{"name":"European Journal of Integrative Medicine","volume":"65 ","pages":"Article 102326"},"PeriodicalIF":1.9000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1876382023001026/pdfft?md5=e89666c92ce5e3f96dfef0890ca9ac0d&pid=1-s2.0-S1876382023001026-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Network pharmacology, molecular docking and experimental verification reveal the mechanism of Yiguanjian decoction in treating acute liver failure\",\"authors\":\"Shuai Wang , Yu Sun , Chunmei Zhang , Bohao Chen , Mei Zhong , Ruili Du , Yuhang Zhou , Guangdong Tong , Lidan Luo\",\"doi\":\"10.1016/j.eujim.2023.102326\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><em>Introduction</em>: The potential targets and action mechanism of Yiguanjian (YGJ) decoction in treating acute liver failure (ALF) were determined using network pharmacology, molecular docking and cell experiments.</p><p><em>Methods</em>: The Pharmacology of Traditional Chinese Medicine Systems (TCMSP) and BATMAN-TCM databases were used to find YGJ decoction targets. The Genecard database was employed to predict targets associated with ALF. Cytascape software was utilised to visualise and select common targets along with establishing a protein–protein interaction (PPI) network. Core targets were screened and putative function was assessed via gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyzes. Molecular docking was performed using AutodockTools, PyMoL and Discovery Studio software to verify the correlation between the YGJ decoction and selected targets. MTT assay was conducted to determine the effect of the YGJ decoction on the viability of Huh-7 human hepatoma cells. The effects of the YGJ decoction on the expression of putative targets in Huh-7 cells were determined via western blot and quantitative real-time polymerase chain reaction analyzes.</p><p><em>Results</em>: Overall, 9153 YGJ decoction and 576 ALF-related targets were obtained, and 469 YGJ decoction and ALF cross targets were obtained. Of these, 20 key targets, including AKT1, estrogen receptor 1 (ESR1), catalase (CAT), interleukin-1β (IL-1β) and discs large homolog 4 (DLG4), were selected from the PPI network. GO function enrichment analysis revealed that these targets were primarily associated with regulating system processes, cell body, oxidoreductase activity and other processes. An enrichment analysis using the KEGG pathway database revealed that the treatment of ALF using the YGJ decoction was primarily associated with the AGE-RAGE, cGMP-PKG and HIF-1 signalling pathways. Molecular docking indicated that quercetin, stigmasterol and β- sitosterol as well as AKT1, ESR1, CAT, IL-1β and DLG4 exhibited good binding affinity. <em>In vitro</em> experiments revealed that the YGJ decoction significantly reversed lipopolysaccharide (LPS)-induced apoptosis (<em>P</em> < 0.01), inhibited LPS-induced increase in IL-1β and ESR1 levels and upregulated LPS-induced decrease in AKT1, CAT and DLG4 levels (<em>P</em> < 0.05).</p><p><em>Conclusions</em>: The YGJ decoction alleviates ALF by regulating multiple targets and its action mechanism may be associated with ameliorating oxidative stress and inflammation.</p></div>\",\"PeriodicalId\":11932,\"journal\":{\"name\":\"European Journal of Integrative Medicine\",\"volume\":\"65 \",\"pages\":\"Article 102326\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1876382023001026/pdfft?md5=e89666c92ce5e3f96dfef0890ca9ac0d&pid=1-s2.0-S1876382023001026-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Integrative Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1876382023001026\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"INTEGRATIVE & COMPLEMENTARY MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Integrative Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1876382023001026","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
Network pharmacology, molecular docking and experimental verification reveal the mechanism of Yiguanjian decoction in treating acute liver failure
Introduction: The potential targets and action mechanism of Yiguanjian (YGJ) decoction in treating acute liver failure (ALF) were determined using network pharmacology, molecular docking and cell experiments.
Methods: The Pharmacology of Traditional Chinese Medicine Systems (TCMSP) and BATMAN-TCM databases were used to find YGJ decoction targets. The Genecard database was employed to predict targets associated with ALF. Cytascape software was utilised to visualise and select common targets along with establishing a protein–protein interaction (PPI) network. Core targets were screened and putative function was assessed via gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyzes. Molecular docking was performed using AutodockTools, PyMoL and Discovery Studio software to verify the correlation between the YGJ decoction and selected targets. MTT assay was conducted to determine the effect of the YGJ decoction on the viability of Huh-7 human hepatoma cells. The effects of the YGJ decoction on the expression of putative targets in Huh-7 cells were determined via western blot and quantitative real-time polymerase chain reaction analyzes.
Results: Overall, 9153 YGJ decoction and 576 ALF-related targets were obtained, and 469 YGJ decoction and ALF cross targets were obtained. Of these, 20 key targets, including AKT1, estrogen receptor 1 (ESR1), catalase (CAT), interleukin-1β (IL-1β) and discs large homolog 4 (DLG4), were selected from the PPI network. GO function enrichment analysis revealed that these targets were primarily associated with regulating system processes, cell body, oxidoreductase activity and other processes. An enrichment analysis using the KEGG pathway database revealed that the treatment of ALF using the YGJ decoction was primarily associated with the AGE-RAGE, cGMP-PKG and HIF-1 signalling pathways. Molecular docking indicated that quercetin, stigmasterol and β- sitosterol as well as AKT1, ESR1, CAT, IL-1β and DLG4 exhibited good binding affinity. In vitro experiments revealed that the YGJ decoction significantly reversed lipopolysaccharide (LPS)-induced apoptosis (P < 0.01), inhibited LPS-induced increase in IL-1β and ESR1 levels and upregulated LPS-induced decrease in AKT1, CAT and DLG4 levels (P < 0.05).
Conclusions: The YGJ decoction alleviates ALF by regulating multiple targets and its action mechanism may be associated with ameliorating oxidative stress and inflammation.
期刊介绍:
The European Journal of Integrative Medicine (EuJIM) considers manuscripts from a wide range of complementary and integrative health care disciplines, with a particular focus on whole systems approaches, public health, self management and traditional medical systems. The journal strives to connect conventional medicine and evidence based complementary medicine. We encourage submissions reporting research with relevance for integrative clinical practice and interprofessional education.
EuJIM aims to be of interest to both conventional and integrative audiences, including healthcare practitioners, researchers, health care organisations, educationalists, and all those who seek objective and critical information on integrative medicine. To achieve this aim EuJIM provides an innovative international and interdisciplinary platform linking researchers and clinicians.
The journal focuses primarily on original research articles including systematic reviews, randomized controlled trials, other clinical studies, qualitative, observational and epidemiological studies. In addition we welcome short reviews, opinion articles and contributions relating to health services and policy, health economics and psychology.