Integrating Network Pharmacology and RT-qPCR Analysis to Investigate the Mechanisms Underlying ZeXie Decoction-Mediated Treatment of Non-alcoholic Fatty Liver Disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Wu J
PROVIDER: S-EPMC8458890 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundChronic atrophic gastritis (CAG) is an important stage in the normal gastric mucosa's transformation into gastric cancer. Huazhuojiedu decoction (HZJD), a Chinese herbal preparation, has proven clinically effective to treat CAG. However, few studies have explored the mechanism of HZJD in CAG treatment.PurposeThis study aimed to shed light on the mechanisms underlying HZJD decoction CAG treatment using a network pharmacology approach and experimental validation.MethodsThe active components of HZJD decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Their targets were predicted through the SwissTargetPrediction database. Disease targets were screened using the GeneCards database. The disease and drug prediction targets were intersected to select the common potential therapeutic targets, which then were input into the Search Tool for the Retrieval of Interacting Genes to build a protein-protein interaction network. The "herb-compound-target-disease" and the "herb-target-pathway" network diagrams were constructed in Cytoscape 3.3.0. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of effective targets were performed using the Database for Annotation, Visualization, and Integrated Discovery. Finally, the core targets were preliminarily verified by CAG rat model. The gastric mucosa's histopathological changes were observed via hematoxylin-eosin staining. The expressions of MAPK1, AKT1, TNF, VEGFA, and EGFR were detected by western blot and quantitative real-time reverse transcription-polymerase chain reaction.ResultsA total of 155 nodes, including 20 putative targets of HZJD decoction, were selected as core hubs based on topological importance and were closely associated with the regulation of cell proliferation, apoptotic process, and cancer-related pathways (AKT1, TNF, VEGFA, and EGFR) in CAG. Further animal experiments showed that the expression of AKT1 in CAG rats was significantly increased, which was suppressed by HZJD decoction. TNF and VEGFA expression increased in the model group, but did not change in the HZJD group. MAPK1 and EGFR expression showed no significant differences among control, model, and HZJD groups.ConclusionTaken together, the results suggest that the components of HZJD decoction can alleviate and prevent the severity of gastric precancerous lesions via AKT1 inhibition in CAG.
| S-EPMC7735863 | biostudies-literature
Project description:BackgroundNon-alcoholic fatty liver (NAFLD) is a chronic disease worldwide, which poses a huge threat to human health. Xiaochaihu decoction is a well-known traditional Chinese medicine prescription. It has been proven effective in treating NAFLD but its mechanism is still unclear.ObjectiveMultiple mechanisms of Xiaochaihu decoction are explored by identifying and connecting potential targets and active ingredients in the treatment of NAFLD.MethodsActive ingredients and related targets of seven herbs were collected from TCMSP database. The related targets of NAFLD were obtained from Genes cards database, TDD and OMIM database. The intersected targets of disease targets and drug targets were input into STRING database to construct protein-protein interaction network. DAVID database was used for GO enrichment analysis and KEGG enrichment analysis.ResultsAfter screening and removal of duplicates, a total of 145 active ingredients and 105 potential targets were obtained. PPI network manifested that AKT1, IL6, JUN MAPK8 and STAT3 were the key target proteins. The results of GO enrichment analysis mainly involved cytokine receptor binding, cytokine activity, and heme binding. The results of KEGG analysis suggested that the mechanism mainly involved in AGE-RAGE signaling pathway in diabetic complications, Hepatitis C, fluid shear stress and atherosclerosis. The signaling pathways were further integrated as network manner, including AGE-RAGE signaling pathway in diabetic complications, Fluid shear stress and atherosclerosis, Insulin resistance, HIF-1 signaling pathway, Th17 cell differentiation and IL-17 signaling pathway. The network contained immunity regulation, metabolism regulation and oxidative stress regulation.ConclusionXiaochaihu decoction plays a key role in the treatment of NAFLD with multiple targets and pathways. Immunity regulation, metabolism regulation and oxidative stress regulation consist of the crucial regulation cores in mechanism.Graphical abstractDesign and workflow of this study.
| S-EPMC7450930 | biostudies-literature
Project description:BackgroundDenglao Qingguan decoction (DLQGD) has been extensively utilized for the treatment of colds, demonstrating significant therapeutic efficacy. Human Coronavirus 229E (HCoV-229E) is considered a crucial etiological agent of influenza. However, the specific impact and underlying mechanisms of DLQGD on HCoV-229E remain poorly understood.MethodsActive ingredients and targets information of DLQGD were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), literature search, and Swiss ADEM database. The Genecard database was used to collect HCoV-229E related targets. We built an "ingredient-target network" through Cytoscape. Protein - Protein interaction (PPI) networks were mapped using the String database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were enriched using the DAVID database. Then, we used molecular docking techniques to verify the binding activity between the core compounds and the core gene targets. Finally, in vitro experiments were conducted to validate DLQGD's antiviral activity against HCoV-229E and assess its anti-inflammatory effects.ResultsIn total, we identified 227 active components in DLQGD. 18 key targets involved in its activity against HCoV-229E. Notably, the core active ingredients including quercetin, luteolin, kaempferol, β-sitosterol, and apigenin, and the core therapeutic targets were CXCL8, RELA, MAPK14, NFKB1, and CXCL10, all associated with HCoV-229E. KEGG enrichment results included IL-17 signaling pathway, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway and so on. The core active ingredients and the core therapeutic targets and Human Aminopeptidase N (ANPEP) all showed good binding activity by molecular docking verification. In vitro, DLQGD exhibited anti-HCoV-229E activity and anti-inflammatory effects.ConclusionOur study suggests that DLQGD has both effects of anti-HCoV-229E and anti-inflammatory. The core active ingredients (quercetin, luteolin, kaempferol, β-sitosterol, apigenin) and the core therapeutic targets (CXCL8, RELA, MAPK14, NFKB1, CXCL10) may play key roles in the pharmacological action of DLQGD against HCoV-229E.
| S-EPMC10963236 | biostudies-literature
Project description:BackgroundHuangqi Sijunzi decoction (HQSJZD) is a commonly used conventional Chinese herbal medicine prescription for invigorating Qi, tonifying Yang, and removing dampness. Modern pharmacology and clinical applications of HQSJZD have shown that it has a certain curative effect on Alzheimer's disease (AD).MethodsThe active components and targets of HQSJZD were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The genes corresponding to the targets were retrieved using UniProt and GeneCard database. The herb-compound-target network and protein-protein interaction (PPI) network were constructed by Cytoscape. The core targets of HQSJZD were analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The main active compounds of HQSJZD were docked with acetylcholinesterase (AChE). In vitro experiments were conducted to detect the inhibitory and neuroprotective effects of AChE.ResultsCompound-target network mainly contained 132 compounds and 255 corresponding targets. The main compounds contained quercetin, kaempferol, formononetin, isorhamnetin, hederagenin, and calycosin. Key targets contained AChE, PTGS2, PPARG, IL-1B, GSK3B, etc. There were 1708 GO items in GO enrichment analysis and 310 signalling pathways in KEGG, mainly including the cAMP signalling pathway, the vascular endothelial growth factor (VEGF) signalling pathway, serotonergic synapses, the calcium signalling pathway, type II diabetes mellitus, arginine and proline metabolism, and the longevity regulating pathway. Molecular docking showed that hederagenin and formononetin were the top 2 compounds of HQSJZD, which had a high affinity with AChE. And formononetin has a good neuroprotective effect, which can improve the oxidative damage of nerve cells.ConclusionHQSJZD was found to have the potential to treat AD by targeting multiple AD-related targets. Formononetin and hederagenin in HQSJZD may regulate multiple signalling pathways through AChE, which might play a therapeutic role in AD.
| S-EPMC8510793 | biostudies-literature
Project description:ObjectiveThis study aims to explore the therapeutic efficacy of San Zi Yang Qin Decoction (SZ) and its potential mechanism in the treatment of non-alcoholic fatty liver disease (NAFLD) based on network pharmacology and in vivo experiments.MethodsEffective chemicals and targets of SZ were searched in online databases, according to the drug-likeness of compounds and the binomial distribution of targets. A disease-target-chemical network was established using NAFLD-associated genes screened through GeneCards database, Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, animal experiments were conducted to verify the efficacy and mechanism of SZ predicted by network pharmacology. The NAFLD mouse model was established with C57BL/6J mice fed with a high-fat diet for 22 weeks. The mice in the control group were fed with a chow diet. From the 23rd week, the NAFLD mice were treated with intragastric SZ or normal saline for 8 weeks. After the glucose tolerance was measured, the mice were sacrificed, followed by the collection of serum and liver tissues. Pathological changes in liver tissues were examined by H&E staining. Additionally, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum fast blood glucose, and insulin levels were detected. Expression levels of TNF-α of serum and liver tissues were determined by ELISA and qRT-PCR, respectively. Western blot was used to detect the activation of AKT in liver tissues.ResultsA total of 27 effective compounds and 20 targets of SZ were screened. GO analysis uncovered a significant correlation between the targets of SZ and those of NAFLD. KEGG analysis presented the signaling pathways enriched in SZ and NAFLD, including NAFLD, TNF-α, and apoptosis pathways. The area under the curve of major GO and KEGG pathways indicated the potential role of SZ in improving NAFLD. In vivo experiments demonstrated that SZ significantly alleviated hepatosteatosis and inflammatory cell infiltration in liver tissues, reduced serum transaminases, and improved insulin resistance and glucose tolerance of NAFLD mice. The protein level of phospho-AKT was upregulated by SZ. Additionally, SZ treatment obviously impaired the TNF-α level in the serum and liver tissue of NAFLD mice.ConclusionsAccording to the network pharmacology analysis and in vivo experiments, SZ could have therapeutic efficacy for NALFD. The mechanism mainly involves pathways relative to insulin resistance, TNF-α, and apoptosis. Our results provide a scientific basis for SZ in the clinical treatment of NAFLD.
| S-EPMC7810527 | biostudies-literature
Project description:Ashitaba seems to improve glucose intolerance and decrease triglyceride (TG) and total cholesterol (TC), which contribute to the development of non-alcoholic fatty liver disease (NAFLD). However, it remains to be explored the mechanism of Ashitaba in managing NAFLD. We determined the impact of Ashitaba on NAFLD, particularly its underlying mechanisms at the bioinformatic level. The established NAFLD mouse model was treated with or without Ashitaba, and the underlying mechanism was explored using transcriptomics paired with metabolomics. Ashitaba reduced obesity and liver steatosis in NAFLD mice. It identified 429 differentially expressed genes (DEGs) and verified 45 differential metabolites, especially those that alleviate NAFLD via the FXR signaling pathway. Our data may provide insight into the therapeutic impact of Ashitaba in the management of NAFLD and may be useful in clinical interventions for NAFLD.
| S-EPMC10618682 | biostudies-literature
Project description:Herbal drugs have drawn substantial interest as effective analgesic agents; however, their therapeutic mechanisms remain to be fully understood. To address this question, we performed a network pharmacology study to explore the system-level mechanisms that underlie the analgesic activity of Jakyak-Gamcho decoction (JGd; Shaoyao-Gancao-Tang in Chinese and Shakuyaku-Kanzo-To in Japanese), an herbal prescription consisting of Paeonia lactiflora Pallas and Glycyrrhiza uralensis Fischer. Based on comprehensive information regarding the pharmacological and chemical properties of the herbal constituents of JGd, we identified 57 active chemical compounds and their 70 pain-associated targets. The JGd targets were determined to be involved in the regulation of diverse biological activities as follows: calcium- and cytokine-mediated signalings, calcium ion concentration and homeostasis, cellular behaviors of muscle and neuronal cells, inflammatory response, and response to chemical, cytokine, drug, and oxidative stress. The targets were further enriched in various pain-associated signalings, including the PI3K-Akt, estrogen, ErbB, neurotrophin, neuroactive ligand-receptor interaction, HIF-1, serotonergic synapse, JAK-STAT, and cAMP pathways. Thus, these data provide a systematic basis to understand the molecular mechanisms underlying the analgesic activity of herbal drugs.
| S-EPMC7732394 | biostudies-literature
Project description:BackgroundAsthma is a chronic inflammatory disease characterized by Th2-predominant inflammation and airway remodeling. Modified Guo Min decoction (MGMD) has been an extensive practical strategy for allergic disorders in China. Although its potential anti-asthmatic activity has been reported, the exact mechanism of action of MGMD in asthma remains unexplored.MethodsNetwork pharmacology approach was employed to predict the active components, potential targets, and molecular mechanism of MGMD for asthma treatment, including drug-likeness evaluation, oral bioavailability prediction, protein-protein interaction (PPI) network construction and analysis, Gene Ontology (GO) terms, and Reactome pathway annotation. Molecular docking was carried out to investigate interactions between active compounds and potential targets.ResultsA total of 92 active compounds and 72 anti-asthma targets of MGMD were selected for analysis. The GO enrichment analysis results indicated that the anti-asthmatic targets of MGMD mainly participate in inflammatory and in airway remolding processes. The Reactome pathway analysis showed that MGMD prevents asthma mainly through regulation of the IL-4 and IL-13 signaling and the specialized pro-resolving mediators (SPMs) biosynthesis. Molecular docking results suggest that each bioactive compounds (quercetin, wogonin, luteolin, naringenin, and kaempferol) is capable to bind with STAT3, PTGS2, JUN, VEGFA, EGFR, and ALOX5.ConclusionThis study revealed the active ingredients and potential molecular mechanism by which MGMD treatment is effective against airway inflammation and remodeling in asthma through regulating IL-4 and IL-13 signaling and SPMs biosynthesis.
| S-EPMC8100455 | biostudies-literature
Project description:ObjectiveTo investigate the protective effects and molecular mechanisms of Lizhong decoction (, LZD) against non-alcoholic fatty liver disease (NAFLD).MethodsMale Wistar rats were fed a high-fat diet for four weeks to induce NAFLD, and were administered LZD by gavage for four weeks. Potential therapeutic targets for NAFLD were analyzed using network pharmacology. Liver pathology was evaluated using Oil Red O and hematoxylin-eosin staining. Furthermore, mitochondrial function, lipid metabolism, oxidative stress, and inflammatory response were examined.ResultsRats with NAFLD exhibited high levels of hepatic damage and cholesterol deposition. Moreover, apoptosis was increased, superoxide dismutase and glutathione content were reduced, malondialdehyde content was increased, and the protein expression of inflammatory cytokines and p-c-Jun N-terminal kinase was increased. The LZD treatment ameliorated mitochondrial dysfunction, reduced liver damage, inhibited oxidative stress and inflammatory response, upregulated peroxisome proliferator-activated receptor (PPAR)-γ expression, and suppressed dipeptidyl peptidase 4 (DPP4) expression in the liver.ConclusionIt was found that LZD alleviates NAFLD by activating PPAR-γ and inhibiting DPP4.
| S-EPMC9924662 | biostudies-literature
Project description:Background and aimChuanxiong Renshen decoction (CRD) is a traditional Chinese medicine compound used to treat Alzheimer's disease (AD). However, the effects and active ingredients of CRD and its mechanism have not been clarified. We aimed to determine the neuroprotective effects of CRD in a triple-transgenic mouse model of AD (3 × Tg-AD) and investigate the possible active ingredients and their mechanisms.MethodsMorris water maze (MWM) tests were used to determine the protective effect of CRD on learning and memory ability. Afterward, we used brain tissue staining, immunofluorescent staining and western blotting to detect the neuroprotective effects of CRD. Ultraperformance liquid-chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) was applied to determine the ingredients of CRD, and the potential AD targets were obtained from DisGeNET and the GeneCards database. The protein‒protein interaction (PPI) network was built with the additional use of STRING 11.0. Metascape was used in the pathway enrichment analysis. Discovery Studio 2016 (DS) software was used to analyze the binding ability of CRD and AD-related genes. Finally, we verified the regulatory effect of CRD on the predicted core targets EGFR and CASP3 by western blotting.ResultsOur study indicated that CRD can significantly improve learning and memory, reduce the expression of Aβ and protect neurons. A total of 95 ingredients were identified in the CRD. Then, 25 ingredients were identified in serum, and 5 ingredients were identified in the brain tissue homogenate. PPI network analysis identified CASP3, EGFR, APP, CNR1, HIF1A, PTGS2 and MTOR as hub targets. KEGG and GO analyses revealed that the TNF signaling pathway and MAPK signaling pathway were enriched in multiple targets. The results of molecular docking proved that the binding of the ingredients with potential key targets was excellent. The western blotting results showed that CRD could significantly reduce the expression of CASP3 and EGFR in the hippocampus of 3 × Tg-AD mice. Combined with literature analysis, we assumed the neuroprotective effect of CRD on AD may occur through regulation of the MAPK signaling pathway.ConclusionCRD significantly alleviated injury in 3 × Tg-AD mice. The possible active ingredients are ferulic acid, rutin, ginsenoside Rg1 and panaxydol. The therapeutic effect of CRD on AD is achieved through the downregulation of CASP3 and EGFR. The neuroprotective effect of CRD on AD may occur through regulation of the MAPK signaling pathway.
| S-EPMC9789652 | biostudies-literature