Interpreting the Molecular Mechanisms of Yinchenhao Decoction on Hepatocellular Carcinoma through Absorbed Components Based on Network Pharmacology.
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ABSTRACT:
SUBMITTER: Sun J
PROVIDER: S-EPMC8159653 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hepatocellular carcinoma (HCC) is one of the most fatal cancers across the world. Chinese medicine has been used as adjunctive or complementary therapy for the management of HCC. Huachansu belongs to a class of toxic steroids isolated from toad venom that has important anti-cancer property. This study was aimed to identify the bioactive constituents and molecular targets of Huachansu capsules (HCSCs) for treating HCC using network pharmacology analysis and experimental assays. The major bioactive components of HCSCs were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A series of network pharmacology methods including target prediction, pathway identification, and network establishment were applied to identify the modes of action of HCSCs against HCC. Furthermore, a series of experiments, including MTT, clonogenic assay, 3-D transwell, wound healing assay, as well as flow cytometry, were conducted to verify the inhibitory ability of HCSCs on HCC in vitro. The results showed that 11 chemical components were identified from HCSCs. The network pharmacological analysis showed that there were 82 related anti-HCC targets and 14 potential pathways for these 11 components. Moreover, experimental assays confirmed the inhibitory effects of HCSCs against HCC in vitro. Taken together, our study revealed the synergistic effects of HCSCs on a systematic level, and suggested that HCSCs exhibited anti-HCC effects in a multi-component, multi-target, and multi-pathway manner.
| S-EPMC7145978 | biostudies-literature
Project description:BackgroundCholangiocarcinoma refers to an epithelial cell malignancy with poor prognosis. Yinchenhao decoction (YCHD) showed positive effects on cancers, and associations between YCHD and cholangiocarcinoma remain unclear. This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma.MethodsBy the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods.Results32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions.ConclusionsAs predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effectsthrough multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.
| S-EPMC7818939 | biostudies-literature
Project description:BACKGROUND:Globally, more than 170 million people are infected with hepatitis C virus, a major cause of cirrhosis and hepatocellular carcinoma. The Yinchenhao Decoction (YCHD) is a classic formula comprising three herbal medicines. This decoction have long been used in China for clinically treating acute and chronic infectious hepatitis and other liver and gallbladder damp heat-accumulation disorders. METHODS:In this study, we identified 32 active ingredients and 200 hepatitis C proteins and established a compound-predicted target network and a hepatitis C protein-protein interaction network by using Cytoscape 3.6.1. Then, we systematically analyzed the potential targets of the YCHD for the treatment of hepatitis C. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by the Kyoto Encyclopedia of Genes and Genomes and gene ontology analyses. RESULTS:This study adopted a network pharmacology approach, mainly comprising target prediction, network construction, module detection, functional enrichment analysis, and molecular docking to systematically investigate the mechanisms of action of the YCHD in hepatitis C. The targets of the YCHD in the treatment of hepatitis C mainly involved PIK3CG, CASP3, BCL2, CASP8, and MMP1. The module and pathway enrichment analyses showed that the YCHD had the potential to influence varieties of biological pathways, including the TNF signaling pathway, Ras signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, and pathways in cancer, that play an important role in the pathogenesis of hepatitis C. CONCLUSION:The results of this study preliminarily verified the basic pharmacological effects and related mechanisms of the YCHD in the treatment of hepatitis C.
| S-EPMC7076901 | biostudies-literature
Project description:Shuanglian decoction (SLD) is traditionally used to treat hepatocellular carcinoma (HCC) in the clinical practice of traditional Chinese medicine. However, its mechanisms of action and molecular targets for the treatment of HCC are not clear. The active compounds of SLD were collected and their targets were identified. HCC-related targets were obtained by analyzing the differentially expressed genes between HCC patients and healthy individuals. Protein-protein interaction (PPI) data were then obtained and PPI networks of SLD putative targets and HCC-related targets were visualized and merged to identify the candidate targets for SLD against HCC. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out. The gene-pathway network was constructed to screen the key target genes. In total, 35 active compounds and 31 targets of SLD were identified. In total, 245 differentially expressed genes with P values <0.005 and |log2 (fold change)| > 1 were identified between HCC patients and control groups, and 68 target genes associated with HCC were finally identified. Twenty-one pathways including cellular senescence, p53 signaling pathway, and cell cycle were significantly enriched. CYP3A4 was the core gene and other several genes including CYP1A2, PPP3CA, PTGS2, CCCNB1, and CDK1 were the key genes in the gene-pathway network of SLD for the treatment of HCC. The results indicated that SLD's effects against HCC may relate to the regulation of an antioxidant function through specific biological processes and related pathways. This study demonstrates the application of network pharmacology in evaluating mechanisms of action and molecular targets of complex herbal formulations.
| S-EPMC7808160 | biostudies-literature
Project description:Sho-saiko-to is a well-known traditional Chinese medicine compound and is considered to have therapeutic effects against many diseases, including thyroid cancer (TC). However, the mechanisms and therapeutic targets of Sho-saiko-to against TC remain unclear. In this study, network pharmacology, molecular docking, and cell experiments were combined to predict and verify the targets and mechanisms of the active ingredients of Sho-saiko-to against TC. The results demonstrated that the main chemical ingredients of Sho-saiko-to could suppress the viability and proliferation of TC cells, promote apoptosis through the caspase3 pathway, and induce autophagy through the PI3K-AKT pathway. In addition, Sho-saiko-to could also induce the redifferentiation of anaplastic thyroid cancer. Our study provides a novel approach for treating differentiated thyroid cancer (DTC) or radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC).
| S-EPMC8991932 | biostudies-literature
Project description:BackgroundPneumonia is a common respiratory disorder, which brings an enormous financial burden to the medical system. However, the current treatment options for pneumonia are limited because of drug resistance and side effects. Our previous study preliminarily confirmed that Yinlai Decoction (YD), a common prescription for pneumonia in clinical practice, can regulate the expression of inflammatory factors, but the mechanisms are unknown yet.MethodsIn our work, a method named network pharmacology was applied, which investigated the underlying mechanisms of herbs based on a variety of databases. We obtained bioactive ingredients of YD on TCMSP database and collected potential targets of these ingredients by target fishing. Then the pneumonia-related targets database was built by TTD, Drugbank, HPO, OMIM, and CTD. Based on the matching targets between YD and pneumonia, the PPI network was built by STRING to analyze the interactions among these targets and then input into Cytoscape for further topological analysis. DAVID and KEGG were utilized for GO and pathway enrichment analysis. Then rat model based on LPS stimulated pneumonia was used to verify the possible mechanism of YD in treating pneumonia.ResultsSixty-eight active ingredients, 103 potential targets and 8 related pathways, which likely exert a number of effects, were identified. Three networks were constructed using Cytoscape, which were herb-component-network, YD-pneumonia target network, and herb-component-YD target-pneumonia network. YD was verified to treat LPS-induced pneumonia by regulating the inflammatory factor IL-6, which was a predicted target.ConclusionNetwork analysis indicated that YD could alleviate the symptoms and signs of pneumonia through regulating host immune inflammatory response, angiogenesis and vascular permeability, the barrier function of the airway epithelial cells, hormone releasing and cell growth, proliferation, and apoptosis.
| S-EPMC7267769 | biostudies-literature
Project description:ObjectivesTo determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma (HCC) by network pharmacology and experimental in vitro validation.MethodsThe predictive targets of curcumin or HCC were collected from several databases. the identified overlapping targets were crossed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Two of the candidate pathways were selected to conduct an experimental verification. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay was used to determine the effect of curcumin on the viability of HepG2 and LO2 cells. The apoptosis and autophagy of HepG2 cells were respectively detected by flow cytometry and transmission electron microscopy. Besides, western blot and real-time polymerase chain reaction (PCR) were employed to verify the p53 apoptotic pathway and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) autophagy pathway. HepG2 cells were pretreated with pifithrin-α (PFT-α) and GSK690693 for further investigation.ResultsThe 167 pathways analyzed by KEGG included apoptosis, autophagy, p53, and AMPK pathways. The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug, regulation of apoptotic pathway, and so on. The in vitro experiments also confirmed that curcumin can inhibit the growth of HepG2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway. Furthermore, the protein and messenger RNA (mRNA) of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group. The damage-regulated autophagy modulator (DRAM) in the PFT-α-pretreated group was downregulated, and p62 in the GSK690693-pretreated group was upregulated.ConclusionsCurcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1 (ULK1) autophagy pathway, in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.
| S-EPMC9381327 | biostudies-literature
Project description:ObjectiveArsenic trioxide (Pishuang, Pishi, arsenolite, As2O3, and CAS 1327-53-3), a naturally occurring and toxic mineral as a drug for more than 2000 years in China, has been found to have a valuable function in hepatocellular carcinoma (HCC) in recent years. However, its exact mechanism remains to be elucidated. Therefore, this study was intended to explore the potential anti-HCC mechanism of arsenic trioxide through network pharmacology.MethodsThe potential targets of arsenic trioxide were collected from PubChem and TargetNet. HCC targets were obtained from the GeneCards database. Then, a protein-protein interaction (PPI) network of arsenic trioxide and HCC common targets was established using STRING. GO and KEGG pathway enrichment analyses were performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Finally, an arsenic trioxide-target-pathway-HCC network was built by Cytoscape 3.2.1, and network topological analysis was carried out to screen the key candidate targets.ResultsA total of 346 corresponding targets of arsenic trioxide and 521 HCC-related targets were collected. After target mapping, a total of 52 common targets were obtained. GO analysis showed that the biological process was mainly involved in the negative regulation of cellular senescence, response to tumor necrosis factor, and cellular response to hypoxia. Molecular functions included NF-kappa B binding, enzyme binding, p53 binding, and transcription factor binding. Cellular components mainly were replication fork, ESC/E(Z) complex, RNA polymerase II transcription factor complex, and organelle membrane. KEGG pathways were mainly enriched in the PI3K-Akt signaling pathway, VEGF signaling pathway, p53 signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, AMPK signaling pathway, NF-kappa B signaling pathway, FoxO signaling pathway, ErbB signaling pathway, and MAPK signaling pathway. In the arsenic trioxide-target-pathway-HCC network, targets such as AKT1, RAF1, RELA, TP53, and PTEN had a higher degree. Conclusions. Our study showed that key targets of arsenic trioxide were mainly involved in multiple biological processes and pathways. It provided a theoretical basis for the screening of drug targets.
| S-EPMC8648446 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a complex and refractory malignant tumor, ranking the third cause of cancer-related deaths worldwide. Lenvatinib is currently employed to treat advanced, unresectable HCC as a first-line drug. The purpose of this study was to explore the pharmacological mechanisms of lenvatinib acting on HCC through the analysis of differential expressed genes based on network pharmacology. The target genes of lenvatinib were collected from PubChem, SwissTargetPrediction, PharmMapper, and BATMAN-TCM online public databases. In addition, related gene targets for HCC were obtained using NCBI Gene Expression Omnibus (NCBI-GEO) database. Afterward, the protein-protein interaction (PPI) network was established to visualize and understand the interaction relationships of overlapping gene targets from both lenvatinib and HCC. Furthermore, according to the data obtained, Gene Ontology (GO) analysis indicated that these intersectant genes were mainly enriched in response to xenobiotic stimulus, gland development, ion channel complex, membrane raft, and steroid binding. Besides, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that the therapeutic effects of lenvatinib on HCC probably involved bile secretion, MAPK signaling pathway, cGMP-PKG signaling pathway, PI3K-Akt signaling pathway, and Ras signaling pathway. Moreover, a total of six key differential genes, namely, ALB, CCND1, ESR1, AR, CCNA2, and AURKA, were identified as most significant targets associated with lenvatinib treating HCC and further verified by molecular docking, which demonstrated that lenvatinib had a strong binding efficiency with these six key gene-encoded proteins. Taken together, this study systematically provided new insights for researchers to determine the intervention mechanisms of lenvatinib in HCC therapy.
| S-EPMC9205703 | biostudies-literature
Project description:Type-2 diabetes mellitus (T2DM) and therapy options have been studied increasingly due to their rising incidence and prevalence. The trend of applying traditional Chinese medicine (TCM) to treat T2DM is increasing as a crucial medical care for metabolic dysfunctions. Gegen Qinlian decoction (GQL), a well-known classical TCM formula used in China, has been clinically applied to treat various types of chronic metabolic diseases. However, antidiabetic effects of GQL administration during T2DM have never been studied systematically. We assessed physiological and molecular targets associated with therapeutic effects of GQL by evaluating network topological characteristics. The GQL-related biological pathways are closely associated with antidiabetic effects, including the TNF and PI3K-AKT signaling pathways. Associated primary biological processes such as RNA polymerase II promoter transcription participate in the inflammatory response, oxidative stress reduction, and glucose metabolic process, thereby exerting multiple biological effects on the antidiabetic mechanism. Furthermore, our results showed that GQL can affect blood glycemic levels and ameliorate inflammatory symptoms, and liver and pancreas tissue injury in high-fat diet plus streptozotocin-induced diabetic mice. In vivo and in vitro experiments confirmed that antidiabetic effects of GQL were associated with a modulation of the TNF and PI3K-AKT-MTOR pathways.
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