Network Pharmacology of Yougui Pill Combined with Buzhong Yiqi Decoction for the Treatment of Sexual Dysfunction

Purpose. We aimed to find the possible key targets of Yougui pill and Buzhong Yiqi decoction for the treatment of sexual dysfunction. Materials and Methods. The composition of Yougui pill combined with Buzhong Yiqi decoction was obtained, and its effective components of medicine were screened using ADME; the component target proteins were predicted and screened based on the TCMSP and BATMAN databases. Target proteins were cross-validated using the CTD database. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for target proteins using the Cytoscape plugin ClueGO + CluePedia and the R package clusterProfiler, respectively. Subsequently, protein-protein interaction (PPI) analyses were conducted using the STRING database. Finally, a pharmacological network was constructed. Results. The pharmacological network contained 89 nodes and 176 relation pairs. Among these nodes, there were 12 for herbal medicines (orange peel, licorice, Eucommia, Aconite, Astragalus, Chinese wolfberry, yam, dodder seed, ginseng, Cornus officinalis, Rehmannia, and Angelica), 9 for chemical components (18-beta-glycyrrhetinic acid, carvacrol, glycyrrhetinic acid, higenamine, nobilin, quercetin, stigmasterol, synephrine, and thymol), 62 for target proteins (e.g., NR3C1, ESR1, PTGS2, CAT, TNF, INS, and TP53), and 6 for pathways (MAPK signaling pathway, proteoglycans in cancer, dopaminergic synapse, thyroid hormone signaling pathway, cAMP signaling pathway, and neuroactive ligand-receptor interaction). Conclusion. NR3C1, ESR1, PTGS2, CAT, TNF, INS, and TP53 may be important targets for the key active elements in the decoction combining Yougui pill and Buzhong Yiqi. Furthermore, these target proteins are relevant to the treatment of sexual dysfunction, probably via pathways associated with cancer and signal transduction.

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Exploration of the Modulatory Property Mechanism of ELeng Capsule in the Treatment of Endometriosis Using Transcriptomics Combined With Systems Network Pharmacology

Frontiers in Pharmacology ◽

10.3389/fphar.2021.674874 ◽

2021 ◽

Vol 12 ◽

Author(s):

Weilin Zheng ◽

Jie Wang ◽

Jiayi Wu ◽

Tao Wang ◽

Yangxue Huang ◽

...

Keyword(s):

Chinese Medicine ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Active Role ◽

Mapk Signaling ◽

Network Pharmacology ◽

Receptor Interaction ◽

Mesenchymal Transition ◽

Beneficial Effects ◽

Function Modules

Endometriosis is a common gynecological disease and causes severe chronic pelvic pain and infertility. Growing evidence showed that traditional Chinese medicine (TCM) plays an active role in the treatment of endometriosis. ELeng Capsule (ELC) is a Chinese medicine formula used for the treatment of endometriosis for several years. However, the mechanisms of ELC have not been fully characterized. In this study, network pharmacology and mRNA transcriptome analysis were used to study various therapeutic targets in ELC. As a result, 40 compounds are identified, and 75 targets overlapped with endometriosis-related proteins. The mechanism of ELC for the treatment of endometriosis is based on the function modules of inducing apoptosis, inhibiting angiogenesis, and regulating immunity mainly through signaling molecules and interaction (neuroactive ligand–receptor interaction), immune system–associated pathways (toll-like receptor signaling pathway), vascular endothelial growth factor (VEGF) signaling, and MAPK signaling pathway based on network pharmacology. In addition, based on RNA-sequence analysis, we found that the mechanism of ELC was predominantly associated with the regulation of the function modules of actin and cytoskeleton, epithelial–mesenchymal transition (EMT), focal adhesion, and immunity-associated pathways. In conclusion, ELC exerted beneficial effects on endometriosis, and the potential mechanism could be realized through functional modules, such as inducing apoptosis and regulating angiogenesis, cytoskeleton, and EMT. This work not only provides insights into the therapeutic mechanism of TCM for treating endometriosis but also offers an efficient way for drug discovery and development from herbal medicine.

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Uncovering the Mechanisms and Molecular Targets of Weibing Formula 1 against Gastritis: Coupling Network Pharmacology with GEO Database

BioMed Research International ◽

10.1155/2021/5533946 ◽

2021 ◽

Vol 2021 ◽

pp. 1-18

Author(s):

Ke Chen ◽

Luojian Zhang ◽

Zhen Qu ◽

Feng Wan ◽

Jia Li ◽

...

Keyword(s):

Real Time ◽

Signaling Pathway ◽

Quantitative Pcr ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Gene Expression Omnibus ◽

Network Pharmacology ◽

Receptor Interaction ◽

Pathway Enrichment Analysis ◽

Real Time Quantitative Pcr

Weibing Formula 1, a classic traditional formula, has been widely used clinically to treat gastritis in recent years. However, the potential pharmacological mechanism of Weibing Formula 1 is still unclear to date. A network pharmacology-based strategy was performed to uncover the underlying mechanisms of Weibing Formula 1 against gastritis. Furthermore, we structured the drug-active ingredients-genes–disease network and PPI network of shared targets, and function enrichment analysis of these targets was carried out. Ultimately, Gene Expression Omnibus (GEO) datasets and real-time quantitative PCR were used to verify the related genes. We found 251 potential targets corresponding to 135 bioactive components of Weibing Formula 1. Then, 327 gastritis-related targets were known gastritis-related targets. Among which, 60 common targets were shared between potential targets of Weibing Formula 1 and known gastritis-related targets. The results of pathway enrichment analysis displayed that 60 common targets mostly participated in various pathways related to Toll-like receptor signaling pathway, MAPK signaling pathway, cytokine-cytokine receptor interaction pathway, chemokine signaling pathway, and apoptosis. Based on the GSE60427 dataset, 15 common genes were shared between differentially expressed genes and 60 candidate targets. The verification results of the GSE5081 dataset showed that except for DUOX2 and VCAM1, the other 13 genes were significantly upregulated in gastritis, which was consistent with the results in the GSE60427 dataset. More importantly, real-time quantitative PCR results showed that the expressions of PTGS2, MMP9, CXCL2, and CXCL8 were significantly upregulated and NOS2, EGFR, and IL-10 were downregulated in gastritis patients, while the expressions of PTGS2, MMP9, CXCL2, and CXCL8 were significantly downregulated and NOS2, EGFR, and IL-10 were upregulated after the treatment of Weibing Formula 1. PTGS2, NOS2, EGFR, MMP9, CXCL2, CXCL8, and IL-10 may be the important direct targets of Weibing Formula 1 in gastritis treatment. Our study revealed the mechanism of Weibing Formula 1 in gastritis from an overall and systematic perspective, providing a theoretical basis for further knowing and application of this formula in the future.

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The role of andrographolide and its derivative in COVID-19 associated proteins and immune system

10.21203/rs.3.rs-35800/v1 ◽

2020 ◽

Author(s):

Yadu Nandan Dey ◽

Pukar Khanal ◽

B. M. Patil ◽

Manish M. Wanjari ◽

Bhavana Srivast ◽

...

Keyword(s):

Immune System ◽

Signaling Pathway ◽

Immune Modulation ◽

Killer Cell ◽

Mapk Signaling ◽

Binding Energies ◽

Gene Set Enrichment Analysis ◽

Spike Protein ◽

Network Pharmacology ◽

Receptor Interaction

Abstract Aim: In view of the strong immunomodulatory and antiviral activity of andrographolide and its derivative, the present study aimed to investigate the binding affinities of andrographolide and its derivative 14-deoxy-11,12-didehydroandrographolide with 3 major targets of COVID-19 i.e. 3CLpro, PLpro and spike protein followed by their gene-set enrichment analysis with special reference to immune modulation.Materials and methods: SMILES of the compounds were retrieved from DigepPred database and the proteins identified were queried in STRING to evaluate the protein-protein interaction and modulated pathways were identified concerning the KEGG database. Drug-likeness and ADMET profiles were evaluated using MolSoft and admet SAR 2.0, respectively. Molecular docking was carried using autodock 4.0.Results: Andrographolide and 14-Deoxy-11,12-didehydroandrographolide were predicted to have a high binding affinity with papain-like protease i.e. -6.7 kcal/mol and -6.5 kcal/mol, respectively while they interact with equal binding energies with 3clpro (-6.8 kcal/mol) and spike protein (-6.9 kcal/mol). Network pharmacology analysis revealed that both compounds modulated the immune system through the regulation of chemokine signaling pathway, Rap1 signaling pathway, Cytokine-cytokine receptor interaction, MAPK signaling pathway, NF-kappa B signaling pathway, Rassignaling pathway, p53 signaling pathway, HIF-1 signaling pathway, and Natural killer cell-mediated cytotoxicity. Although the 14-deoxy-11,12-didehydroandrographolide scored higher drug-likeness character, it showed less potency to interaction with targeted proteins of COVID-19.Conclusion: The study suggests the strong interaction of the andrographolide and its derivative 14-deoxy-11,12-didehydroandrographolide against target proteins associated with COVID-19. Further, network pharmacology analysis elucidated the different pathways of immunomodulation. However, clinical research should be conducted to confirm the current findings.

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Exploring the Mechanisms Underlying the Therapeutic Effect of Xixin Decoction on Alzheimer's Disease Based on Network Pharmacology and Molecular Docking

10.21203/rs.3.rs-562321/v1 ◽

2021 ◽

Author(s):

Zhuo Zhang ◽

Jiang-lin Xu ◽

Ming-qing Wei ◽

Ting Li ◽

Jing Shi

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

Signaling Pathway ◽

Therapeutic Effect ◽

Mapk Signaling ◽

Network Pharmacology ◽

Receptor Interaction ◽

Ppi Network ◽

Active Compounds

Abstract Background and objective: Alzheimer’s disease (AD) has been a worldwide problem, not only the treatment but also the prevention. As a commonly used Chinese Herbal Formula, Xixin Decoction (XXD) has significant therapeutic effect on AD but without clear mechanism. This study was aimed to predict the main active compounds and targets of XXD in the treatment of AD and to explore the potential mechanism by using network pharmacology and molecular docking. Methods: The compounds of XXD were searched in the TCMSP and the TCMID database, and the active compounds were screened based on the ADME model and SwissADME platform. SwissTargetPrediction platform was used to search for the primary candidate targets of XXD. The common targets related to AD obtained by two databases (GeneCards and DisGeNET) were determined as candidate proteins involved in AD. To acquire the related targets of XXD in the treatment of AD, the target proteins related to AD were intersected with the predicted targets of XXD. Then these overlapping targets were imported into the STRING database to build PPI network including hub targets; Cytoscape 3.7.2 software was used to construct the topology analysis for the herb-compound-target network diagram while one of it’s plug-in called CytoNCA was used to calculate degree value to screen the main active compounds of XXD. GO and KEGG pathway enrichment analyses were conducted to explore the core mechanism of action and biological pathways associated with the decoction via Metascape platform. We used AutoDock Vina and PyMOL 2.4.0 softwares for molecular docking of hub targets and main compounds.Results: We determined 114 active compounds which meet the conditions of ADME screening, 973 drug targets, and 973 disease targets. However, intersection analysis screened out 208 shared targets. PPI network identified 9 hub targets, including TP53, PIK3CA, MAPK1, MAPK3, STAT3, AKT1, etc. The 10 main active compounds play a major role in treatment of AD by XXD. Hub targets were found to be enriched in 10 KEGG pathways, involving the Pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, Alzheimer's disease, Neuroactive ligand-receptor interaction, Dopaminergic synapse, Serotonergic synapse and MAPK signaling pathway. The docking results indicated that the 8 hub targets exhibit good binding activity with the 9 main active compounds of XXD.Conclusions: We found the advantages of multi-compounds-multi-targets-multi-pathways regulation to reveal the mechanism of XXD for treating AD based on network pharmacology and molecular docking. Our study provided a theorical basis for further clinical application and experimental research of XXD for anti-AD in the future.

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Exploring the Pharmacological Mechanism of Duhuo Jisheng Decoction in Treating Osteoporosis Based on Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5510290 ◽

2021 ◽

Vol 2021 ◽

pp. 1-21

Author(s):

Zhencheng Xiong ◽

Can Zheng ◽

Yanan Chang ◽

Kuankuan Liu ◽

Li Shu ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Hub Genes ◽

Active Compounds ◽

Treatment Of Osteoporosis ◽

Target Proteins

Objective. The purpose of this work is to study the mechanism of action of Duhuo Jisheng Decoction (DHJSD) in the treatment of osteoporosis based on the methods of bioinformatics and network pharmacology. Methods. In this study, the active compounds of each medicinal ingredient of DHJSD and their corresponding targets were obtained from TCMSP database. Osteoporosis was treated as search query in GeneCards, MalaCards, DisGeNET, Therapeutic Target Database (TTD), Comparative Toxicogenomics Database (CTD), and OMIM databases to obtain disease-related genes. The overlapping targets of DHJSD and osteoporosis were identified, and then GO and KEGG enrichment analysis were performed. Cytoscape was employed to construct DHJSD-compounds-target genes-osteoporosis network and protein-protein interaction (PPI) network. CytoHubba was utilized to select the hub genes. The activities of binding of hub genes and key components were confirmed by molecular docking. Results. 174 active compounds and their 205 related potential targets were identified in DHJSD for the treatment of osteoporosis, including 10 hub genes (AKT1, ALB, IL6, MAPK3, VEGFA, JUN, CASP3, EGFR, MYC, and EGF). Pathway enrichment analysis of target proteins indicated that osteoclast differentiation, AGE-RAGE signaling pathway in diabetic complications, Wnt signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, calcium signaling pathway, and TNF signaling pathway were the specifically major pathways regulated by DHJSD against osteoporosis. Further verification based on molecular docking results showed that the small molecule compounds (Quercetin, Kaempferol, Beta-sitosterol, Beta-carotene, and Formononetin) contained in DHJSD generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes. Conclusion. This study reveals the characteristics of multi-component, multi-target, and multi-pathway of DHJSD against osteoporosis and provides novel insights for verifying the mechanism of DHJSD in the treatment of osteoporosis.

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Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Angelicae Pubescentis Radix in the treatment of rheumatoid arthritis

10.21203/rs.3.rs-445750/v1 ◽

2021 ◽

Author(s):

yanni yang ◽

yirixiati aihaiti ◽

peng xu ◽

haishi zheng

Keyword(s):

Rheumatoid Arthritis ◽

Molecular Docking ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Receptor Interaction ◽

Active Components ◽

Target Proteins ◽

Go Enrichment ◽

Go Enrichment Analysis

Abstract Purpose:To explore the potential target proteins underlying the effect of Angelicae Pubescentis Radix(APR) on rheumatoid arthritis (RA) using a network pharmacology and molecular docking approach .Methods:First, the active components and target proteins of APR and RA related disease targets were obtained from the TCMSP, Gene Card,OMIM,DisGeNET and STRING databases. Then the active ingredient target in the RA network diagram was drawn using Cytoscape 3.7.1 software. Protein-protein interaction analysis, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analyses were carried out using the STRING and David databases. The crystal structures of RA related targets were retrieved from the RCSB PDB database. Finally, the potential active compounds and their related targets were validated using molecular docking technology.Results: Five active components of Angelicae Pubescentis Radix(APR) were screened out, including ammidin, isoimperatorin, beta-sitosterol, O-acetylcolumbianetin and angelicone and 80 key targets including MAPK8,EGFR,PTGS2,CASPASE3,MTOR,SRC,KDR,MAPK1,NOS3 and MAPK14, etc were obtained. GO enrichment analysis showed that 222 biological processes, 34 cell components and 72 molecular functions were identified; KEGG analysis showed that the targets of APR in the treatment of RA were significantly enriched in pathways in cancer, the PI3K−Akt signaling pathway, Proteoglycans in cancer, osteoclast differentiation, neuroactive ligand−receptor interaction, tuberculosis,TNF signaling pathway, serotonergic synapse, Rap1 signaling pathway,cAMP signaling pathway. The results of molecular docking showed that ammidin, isoimperatorin, beta-sitosterol, O-acetylcolumbianetin and angelicone had strong affinity for PTGS2, EGFR and MAPK8.Conclusion: APR treats RA through the characteristics of multi-component, multi-target and multi-pathway regulation.

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Studies of the Anti-Diabetic Mechanism of Pueraria lobata Based on Metabolomics and Network Pharmacology

Processes ◽

10.3390/pr9071245 ◽

2021 ◽

Vol 9 (7) ◽

pp. 1245

Author(s):

Shu Zhang ◽

Qi Ge ◽

Liang Chen ◽

Keping Chen

Keyword(s):

Signaling Pathway ◽

Diabetes Complications ◽

Mapk Signaling ◽

Network Pharmacology ◽

Pueraria Lobata ◽

Insulin Deficiency ◽

Active Ingredients ◽

Foxo Signaling Pathway ◽

Anti Inflammation

Diabetes mellitus (DM), as a chronic disease caused by insulin deficiency or using obstacles, is gradually becoming a principal worldwide health problem. Pueraria lobata is one of the traditional Chinese medicinal and edible plants, playing roles in improving the cardiovascular system, lowering blood sugar, anti-inflammation, anti-oxidation, and so on. Studies on the hypoglycemic effects of Pueraria lobata were also frequently reported. To determine the active ingredients and related targets of Pueraria lobata for DM, 256 metabolites were identified by LC/MS non targeted metabonomics, and 19 active ingredients interacting with 51 DM-related targets were screened. The results showed that puerarin, quercetin, genistein, daidzein, and other active ingredients in Pueraria lobata could participate in the AGE-RAGE signaling pathway, insulin resistance, HIF-1 signaling pathway, FoxO signaling pathway, and MAPK signaling pathway by acting on VEGFA, INS, INSR, IL-6, TNF and AKT1, and may regulate type 2 diabetes, inflammation, atherosis and diabetes complications, such as diabetic retinopathy, diabetic nephropathy, and diabetic cardiomyopathy.

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Network Pharmacology Study of The Mechanism of Anti-Pneumonia Action Mechanism of Gentiana Rhodantha Franch

10.21203/rs.3.rs-539959/v1 ◽

2021 ◽

Author(s):

Jun Luo ◽

Xiusheng Tang ◽

Guotao Shu ◽

Dongxin Tang ◽

Jia Yu ◽

...

Keyword(s):

Chinese Medicine ◽

Signaling Pathway ◽

High Throughput Sequencing ◽

Biological Information ◽

Network Pharmacology ◽

Chemical Components ◽

Sequencing Analysis ◽

Data Set ◽

Annotation Database ◽

Functional Richness

Abstract Background: Serum dragon bile is a Chinese medicine used to treat pneumonia, but its mechanism of action is not clear. Meanwhile, due to the development of microarray and RNA‐sequencing technology, high-throughput sequencing analysis is being used increasingly, and it has been applied as an indispensable tool in many medical fields. Therefore, in this article, we want to employed the bioinformatics approach to explore the relevant pharmacological mechanism of dragon serum bile in the treatment of pneumonia through network pharmacology.Methods: In this paper, the active chemical composition and action target of serum dragon bile are obtained through the pharmacology database (TCMSP) of Chinese medicine system and the literature, and the data set of the intersection of active ingredient and disease target is established, and the protein interoperability network of serum gallbladder action target and pneumonia action target is analyzed by using protein interaction network (PPI). Using the Biological Information Annotation Database (DAVID) for gene ontology (GO) functional richness analysis and based on kyoto Gene and Genomics Encyclopedia (KEGG) pathogenic rich analysis, to predict the mechanism of the role of seroclon bile against pneumonia. Results: Through the network pharmacological prediction, it is shown that the main chemical components of serum dragon bile are quercetin, isoorientin, luteolin, Stigmasterol, vanillic acid, etc, all of which have anti-pneumonia effects. The anti-pneumonia effect of serum dragon bile is mainly regulated by pathways in cancer, Bradder cancer, TNF signaling pathway, Hepatitis B and Non-small cell lung cancer, among which the TNF signaling pathway is more associated with pneumonia. Conclusions: It is concluded from the network pharmacological prediction that serum dragon bile may play an anti-pneumonia role by promoting apoptosis, survival, immunity, etc. Its anti-pneumonia path is closely related to key targets IL6, FOS, CASP3 and AKT1. This study provides theoretical support for the follow-up study of the anti-pneumonia mechanism of serum gentian bile.

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Explore the active ingredients and mechanisms in Musa basjoo pseudostem juice against diabetes based on animal experiment, gas chromatography-mass spectrometer and network pharmacology

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207324666210827112233 ◽

2021 ◽

Vol 24 ◽

Author(s):

Feng Xu ◽

Xiangpei Wang ◽

Xiujuan Wei ◽

Teng Chen ◽

Hongmei Wu

Keyword(s):

Gas Chromatography ◽

Molecular Docking ◽

Signaling Pathway ◽

Mass Spectrometer ◽

Diabetic Rats ◽

Network Pharmacology ◽

Receptor Interaction ◽

Oral Glucose ◽

Active Ingredients ◽

Polar Parts

Background: Musa basjoo pseudostem juice (MBSJ) is a well-known Chinese medicine, and Miao people use MBSJ to treat diabetes. In this work, the active ingredients and molecular mechanism of MBSJ against diabetes were explored. Methods: Anti-diabetic activity of MBSJ was evaluated using diabetic rats, and then the ingredients in the small-polar parts of MBSJ were analyzed by gas chromatography-mass spectrometer (GC-MS). Targets were obtained from several databases to develop the "ingredient-target-disease" network by Cytoscape. A collaborative analysis was carried out using the tools in Cytoscape and R packages, and molecular docking was also performed. Results: MBSJ improved the oral glucose tolerance and insulin tolerance, and reduced fasting blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride, and low-density lipoprotein levels in the serum of diabetic rats. 13 potential compounds were identified by GC-MS for subsequent analysis, including Dibutyl phthalate, Oleamide, Stigmasterol, Stigmast-4-en-3-one, etc. The anti-diabetic effect of MBSJ was related to multiple signaling pathways, including Neuroactive ligand-receptor interaction, Phospholipase D signaling pathway, Endocrine resistance, Rap1 signaling pathway, EGFR tyrosine kinase inhibitor resistance, etc. Molecular docking at least partially verified the screening results of network pharmacology. Conclusion: MBSJ had good anti-diabetic activity. The small-polar parts of MBSJ were rich in anti-diabetic active ingredients. Furthermore, the analysis results showed that the anti-diabetic effect of the small-polar parts of MBSJ may be the result of multiple components, multiple targets, and multiple pathways. The current research results can provide important support for studying the active ingredients and exploring the underlying mechanism of MBSJ against diabetes.

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Anticancer Effects of Emodin on HepG2 Cell: Evidence from Bioinformatic Analysis

BioMed Research International ◽

10.1155/2019/3065818 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Rui-sheng Zhou ◽

Xiong-Wen Wang ◽

Qin-feng Sun ◽

Zeng Jie Ye ◽

Jian-wei Liu ◽

...

Keyword(s):

Signaling Pathway ◽

Hepg2 Cells ◽

Molecular Mechanisms ◽

Mapk Signaling ◽

Ion Concentration ◽

Receptor Interaction ◽

Pathway Enrichment Analysis ◽

Mrna Levels ◽

Hub Genes ◽

Positive Regulation

Hepatocellular carcinoma (HCC) is a primary cause of cancer-related death in the world. Despite the fact that there are many methods to treat HCC, the 5-year survival rate of HCC is still at a low level. Emodin can inhibit the growth of HCC cells invitroand invivo. However, the gene regulation of emodin in HCC has not been well studied. In our research, RNA sequencing technology was used to identify the differentially expressed genes (DEGs) in HepG2 cells induced by emodin. A total of 859 DEGs were identified, including 712 downregulated genes and 147 upregulated genes in HepG2 cells treated with emodin. We used DAVID for function and pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed using STRING, and Cytoscape was used for module analysis. The enriched functions and pathways of the DEGs include positive regulation of apoptotic process, structural molecule activity and lipopolysaccharide binding, protein digestion and absorption, ECM-receptor interaction, complement and coagulation cascades, and MAPK signaling pathway. 25 hub genes were identified and pathway analysis revealed that these genes were mainly enriched in neuropeptide signaling pathway, inflammatory response, and positive regulation of cytosolic calcium ion concentration. Survival analysis showed that LPAR6, C5, SSTR5, GPR68, and P2RY4 may be involved in the molecular mechanisms of emodin therapy for HCC. A quantitative real-time PCR (qRT-PCR) assay showed that the mRNA levels of LPAR6, C5, SSTR5, GPR68, and P2RY4 were significantly decreased in HepG2 cells treated with emodin. In conclusion, the identified DEGs and hub genes in the present study provide new clues for further researches on the molecular mechanisms of emodin.

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