Computer-Aid Molecular Docking Technology in Cereal Mycotoxin Analysis

Computer-aid molecular docking is a simulative process that receptors and ligands recognize each other through energy matching and geometric matching. It is widely used in bioactive compounds simulative screening and preliminary exploring the bioactivity and toxicity of molecular, which plays an important guiding role in toxicity and bioactivity study of molecular entities. In our study, we used the computer-aid molecular docking software-discovery studio 3.1 client to test the mechanism of aflatoxins such as aflatoxin B1, B2, M1, M2, G1, G2 and the results of our experiment help to illustrate the pathway of aflatoxin’s toxication. We also used this technology to test the preliminary toxicity of zearalenone (ZEN) and its two degradation products:α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL), which indicates that these three products possessed significant estrogenic activity. The order of the estrogenic activity is:α-zearalenol > zearalenone >β-zearalenol.

Novel umami peptides from two Termitomyces mushrooms and molecular docking to the taste receptor T1R1/T1R3

Wild edible Termitomyces mushrooms are popular in Southwest China and umami is important flavor qualities of edible mushrooms.This study aimed to understand the umami taste of Termitomyces intermedius and Termitomyces aff.bulborhizus.Ten umami peptides from aqueous extracts were separated using a Sephadex G-15 gel filtration chromatography.The intense umami fraction was evaluated by both sensory evaluation and electronic tongue.They were identified as KLNDAQAPK,DSTDEKFLR,VGKGAHLSGEH,MLKKKKLA,SLGFGGPPGY,TVATFSSSTKPDD,AMDDDEADLLLLAM,VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK.Seven peptides,except VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK were selectively synthesized to verify their taste characteristics.All these 10 peptides had umami or salt taste.The 10 peptides were conducted by molecular docking to study their interaction with identified peptides and the umami taste receptor T1R1/T1R3.All these 10 peptides perfectly docked the active residues in the T1R3 subunit.Our results provide theoretical basis for the umami taste and address the umami mechanism of two wild edible Termitomyces mushrooms.

Exploring the potential mechanism of WuFuYin against hypertrophic scar using network pharmacology and molecular docking

BACKGROUND Hypertrophic scar(HTS)is dermal fibroproliferative disorder,which may cause physiological and psychological problems.Currently,the potential mechanism of WuFuYin(WFY)in the treatment of HTS remained to be elucidated.AIM To explore the potential mechanism of WFY in treating HTS.METHODS Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.HTSrelated genes were obtained from the GeneCards,DisGeNET,and National Center for Biotechnology Information.The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome(KEGG)enrichment analysis.A protein+IBM-protein interaction(PPI)network was developed using STRING database and Cytoscape.To confirm the high affinity between compounds and targets,molecular docking was performed.RESULTS A total of 65 core genes,which were both related to compounds and HTS,were selected from multiple databases.PPI analysis showed that CKD2,ABCC1,MMP2,MMP9,glycogen synthase kinase 3 beta(GSK3B),PRARG,MMP3,and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG)were the hub targets and MOL004941,MOL004935,MOL004866,MOL004993,and MOL004989 were the key compounds of WFY against HTS.The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway.Moreover,by performing molecular docking,we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity.CONCLUSION The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941,MOL004989,and MOL004993 were the main compounds of WFY in HTS treatment.

Network pharmacology combined with molecular docking revealed the potential targets of Coridius chinensis in prostate cancer treatment

BACKGROUND Prostate cancer(PCa)has high morbidity and mortality rates in elderly men.With a history of thousands of years,traditional Chinese medicine derived from insects could be an important source for developing cancer-targeted drugs to prevent tumorigenesis,enhance therapeutic effects,and reduce the risk of recurrence and metastasis.Multiple studies have shown that Coridius chinensis(Cc)has anticancer effects.AIM To elucidate the mechanism of action of Cc against PCa via network pharma-cology and molecular docking.METHODS Potential targets for Cc and PCa were predicted using ChemDraw 19.0 software,the PharmMapper database and the GeneCards database.Then,the STRING database was used to construct the protein–protein interaction network.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment and molecular docking analyses were subsequently conducted to identify the key targets,active ingredients and pathways involved.RESULTS GO and KEGG analyses indicated that the PI3K-Akt signalling pathway was the critical pathway(P value<1.0×10-8).Multiple targeting ingredients that can affect multiple pathways in PCa have been identified in Cc.Seven active compounds(asponguanosines A,asponguanine B,asponguanine C,aspong-pyrazine A,N-acetyldopamine,aspongadenine B and aspongpyrazine B)were selected for molecular docking with 9 potential targets,and the results revealed that aspongpyrazine A and asponguanosine A are the main components by which Cc affects PCa(affinity<-5 kcal/mol,hydrogen bonding),but more studies are needed.CONCLUSION We used network pharmacology to predict the bioactive components and important targets of Cc for the treatment of PCa,supporting the development of Cc as a natural anticancer agent.

Exploring the Mechanism of Action of Glyasperin A in Intervening Menopause Based on Network Pharmacology and Molecular Docking Technology

[Objectives]To investigate the mechanism of action of glyasperin A(GAA)in intervening menopause using network pharmacology and molecular docking technology.[Methods]All target names of the active ingredients were screened using TCMSP,3D model molecules converted into SMILES online tool,Swiss target prediction and literature search.The relevant target genes corresponding to menopause were identified using the Genecards database.Venn 2.1.0 was then used to generate the corresponding Venn diagram.Finally,the protein-protein interaction(PPI)network was constructed using Cytoscape 3.9.1 software.The core targets that were screened underwent enrichment and analysis using the Gene Ontology(GO)biological process and KEGG pathways with the assistance of the DAVID database and bioinformatics.The molecular docking was then verified using AutoDock and Pymol software on the core targets.[Results]This study screened 100 target genes of active ingredients.In the PPI network,ESR1 and AKT1 were found to have a higher degree.The GO and KEGG enrichment analyses revealed that the biological processes primarily involved platelet activation,regulation of circadian rhythms,and regulation of mRNA stability.The signalling pathways included hepatitis B,cytotoxicity,and gastric cancer.The molecular docking results indicated that the key active ingredients and proteins bound well,as evidenced by their small binding energies.[Conclusions]Using a systematic network pharmacology approach,this study predicts the basic pharmacological effects and potential mechanisms of GAA in intervening menopause,which provides a foundation for further research on its pharmacological mechanisms.

Exploring the molecular mechanism of Suoquan pill in the treatment of diabetic kidney disease based on network pharmacology,molecular docking,in vitro experiment

Background:Diabetic kidney disease(DKD)is a microvascular complication of diabetes mellitus and is the main cause of end-stage renal failure.Suoquan pills(SQP)has a variety of pharmacological activities and multiple therapeutic effects,and it is used clinically as a basic formula for the treatment of DKD.Methods:Public databases were used to identify SQP compounds and the potential targets of SQP and DKD.A drug-component-therapeutic target network was constructed.Protein-protein interaction network analysis,Gene Ontology functional analysis,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyse the potential molecular mechanisms of SQP based on common targets of drugs and diseases.Molecular docking simulations were conducted to confirm the binding abity of the core compounds to key targets.The efficacy and predicted molecular mechanisms of SQP were validated using cell counting kit-8 assay,flow cytometry,and western blotting with HK-2 cells as a model.Results:Network pharmacology analysis showed that 26 compounds and 207 potential targets of SQP were involved in the treatment of DKD;boldine,denudatin B,pinocembrin,kaempferoid,and quercetin were considered core compounds,and epidermal growth factor receptor(EGFR)and proto-oncogene,non-receptor tyrosine kinase(SRC)were considered key targets.Gene Ontology enrichment analysis indicated that protein phosphorylation and negative regulation of apoptotic processes are important biological processes in the treatment of DKD by SQP.Molecular docking confirmed the excellent binding abilities of boldine,denudatin B,kaempferide,and quercetin to EGFR and SRC.The results of in vitro experiments showed that treatment with an ethanolic extract of SQP significantly protected HK-2 cells from high glucose-induced cell damage.In addition,the SQP ethanol extract inhibited the phosphorylation of EGFR and SRC,suppressed the apoptosis rate,and regulated apoptosis-related proteins in HK-2 cells under high glucose stress.Conclusion:This study systematically and intuitively illustrated the possible pharmacological mechanisms of SQP against DKD through multiple components,targets,and signalling pathways,especially the inhibition of EGFR and SRC phosphorylation and apoptosis.

Molecular Docking Studies on Streptomycin Antileishmanial Activity

Resistance to pentavalent antimonial drugs and the lack of vaccines make it urgent to find novel therapeutic options to treat Leishmaniasis, a tropical disease caused by the Leishmania protozoan parasite. The study reported here is to investigate if Streptomycin, an aminoglycoside, and Amphotericin B, the second-line treatment drug, exhibit antileishmanial activity through a similar mechanism. By using MOE (Molecular Operating Environment), we performed molecular docking studies on these drugs binding to a range of targets including ribosome targets in Leishmania and H. sapiens. Our study shows that the two drugs do not bind to the same pockets in Leishmania targets but to the same pockets in the human ribosome, with some differences in interactions. Moreover, our 2D maps indicated that Amphotericin B binds to the A-site in the human cytoplasmic ribosome, whereas streptomycin does not.

Mechanistic study of lipid metabolism disorders in diabetic kidney disease treated with GLQMP based on network pharmacology,molecular docking and in vitro experiments

Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.

Exploring the molecular mechanism of action of curcumin for the treatment of diabetic retinopathy,using network pharmacology,molecular docking,and molecular dynamics simulation

Background:Based on network pharmacology and molecular docking,the present study investigated the mechanism of curcumin(CUR)in diabetic retinopathy treatment.Methods:Based on the DisGeNET,Swiss TargetPrediction,GeneCards,Online Mendelian Inheritance in Man,Gene Expression Omnibus,and Comparative Toxicogenomics Database,the intersection core targets of CUR and diabetic retinopathy were identified.The intersection target was imported into the STRING database to obtain the protein-protein interaction map.According to the Database for Annotation,Visualization and Integrated Discovery database,the intersected targets were enriched in Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes pathways.Then Cytoscape 3.9.1 is used to make the drug-target-disease-pathway network.The mechanism of CUR and diabetic retinopathy was further verified by molecular docking and molecular dynamics simulation.Results:There were 203 intersecting targets of CUR and diabetic retinopathy identified.1320 GO entries were enriched for GO functions,which were primarily involved in the composition of cells such as identical protein binding,protein binding,enzyme binding,etc.It was found that 175 pathways were enriched using Kyoto Encyclopedia of Genes and Genomes pathway enrichment methods,which were mainly included in the lipid and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,pathways in cancer,etc.In the molecular docking analysis,CUR was found to have a good ability to bind to the core targets of albumin,IL-1B,and IL-6.The binding of albumin to CUR was further verified by molecular dynamics simulation.Conclusion:As a result of this study,CUR may exert a role in the treatment of diabetic retinopathy through multi-target and multi-pathway regulation,which indicates a possible direction of future research.

The Mechanism of Celastrol in the Treatment of Metastatic Lung Adenocarcinoma Revealed by Network Pharmacology and Molecular Docking

Background: Celastrol is an active ingredient extracted from Traditional Chinese Medicine (TCM), which can restrain the progression of lung cancer, whereas its underlying mechanism is unclear. In our study, the underlying mechanism of celastrol in the treatment of lung adenocarcinoma (LUAD) with metastasis was investigated by network pharmacology and molecular docking. Method: Potential targets of celastrol were collected from TCMSP, Batman-TCM and GeneCard database, and its potential targets were predicted using the STP platform and the TargetNet server. Metastasis marker genes (MGs) were obtained from the HCMDB. The genes correlated with LUAD were gathered from the GeneCard and OMIM database. And the common targets among celastrol potential targets, MGs and LUAD were analyzed. The protein-protein interaction (PPI) networks were obtained from the STRING database. SangerBox and the Xiantao bioinformatics tool were applied to visualize GO and KEGG analysis. Molecular docking tested the binding affinity between celastrol and core genes. Result: A total of 107 targets of celastrol against metastasis LUAD were obtained. The core targets were obtained from the PPI network, namely AKT1, JUN, MYC, STAT3, IL6, TNF, NFKB1, BCL2, IL1B, and HIF1A. GO and KEGG enrichment analysis indicated celastrol for the treatment of metastasis LUAD most refers to cellular response to chemical stress, DNA-binding transcription factor binding, transcription regulator complex and pathways in cancer. And some of these targets are associated with differential expressions and survival rates in LUAD. Moreover, Molecular docking shows celastrol can bind with BCL2 well by hydrogen bond and hydrophobic interaction. Conclusion: This finding roundly expounded the core genes and potential mechanisms of celastrol for the treatment of metastasis LUAD, offering the theoretical basis and antitumor mechanism of TCM in the treatment of lung cancer.

Mechanism of Anti-tumor Effects of Viola Medicinal Materials Based on Network Pharmacology and Molecular Docking

[Objectives]To explore the relationship between anti-tumor components,targets,and pathways involved in Viola medicinal materials,study its main active components,and evaluate its inhibitory activity.[Methods]Through network pharmacological analysis,molecular docking simulation experiments and in vitro experiments,the main components and corresponding targets of Viola were screened out,and their anti-tumor signaling pathways were confirmed.MTT colorimetric assay was used to investigate the inhibitory effect of different extraction layers of Viola on the growth of tumor cells.[Results]18 anti-tumor active components such as 2α,19α-Dihydroxyursolic acid,Corlumine,Madolin U,Trifolirhizin and etc.,and 52 action targets such as PTGS2,PTGS1,P2RX7,MMP1,and GABRB3,and anti-tumor signaling pathways were confirmed.The results of molecular docking showed that all the selected Viola compounds had good binding activity.The results of MTT colorimetric assay showed that the petroleum ether layer and n-butanol layer had a good inhibitory effect on the growth of tumor cell lines.[Conclusions]Viola medicinal materials have the potential of anti-tumor,triterpenoids and flavonoids may be the main active components,and the petroleum ether layer and n-butanol layer have better inhibitory effect on the growth of tumor cells.

Potential pharmacological mechanisms of digallate in the treatment of enteritis based on network pharmacology and molecular docking

Background:In order to investigate the possible pharmacological mechanism of digallate in Galla Chinensis for treating enteritis,providing reference for the search and exploration of effective drugs for treating enteritis.Method:Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PharmMapper,DisGeNET,DrugBank,and GeneCards databases were used to obtain drug and disease-related target information.Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were performed,and the main therapeutic pathways and targets were identified by combining protein-protein interaction networks and cytoHubba plug-in.Molecular docking was used to validate the results.Result:297 drug related targets,2436 disease related targets,and 66 target points related to digallate were predicted to be associated with enteritis.10 related signal pathways and 10 key genes were identified.Conclusion:Digallate may be utilized to treat enteritis by acting on similar pathways,such those related to pathways in cancer,lipid and atherosclerosis,proteoglycans in cancer,Rap1 signaling pathway,PI3K-Akt signaling pathway and other targets such as IGF1,EGFR,SRC,IGF1R,PPARG.

Molecular Docking Studies of Botanical Beverage Mix Berries (LIFEGREENTM) against Breast Cancer Cells from Targeted Protein 1QQG, 7B5Q & 7B5O & Uterine Fibroid from Targeted Protein 2AYR, 6T41 & 3GRF

Fibroids, also called leiomyomas or myomas, are communal tumors of the muscle or uterine wall that affect about 20% of females who are of reproductive age. They can look as if singly or in clusters, and they often cease to grow after menopause. Fibroids can be classified as intramural, sub serosal, pedunculated, or submucosal based on where they are positioned in the uterus. Although fibroids are benign, they can grow quickly and cause a range of symptoms, such as pelvic pressure, heavy menstrual flow, and infertility. As a result, fibroids are a main reason behind hysterectomy surgeries. The majority of cases of breast cancer are ductal and lobular cancers, making it the second utmost common cancer in women international. Gene mutations like those in BRCA1 or BRCA2 knowingly raise the risk of breast and other cancers, typically with an earlier cancer onset. Cancer risk is influenced by a complex interplay of genetic abnormalities, environmental factors, and lifestyle selections. Further research into these relations is domineering. Although they are common in uterine leiomyomas, especially multiple leiomyomas, MED12 mutations do not significantly correlate with tumor size. These mutations have also been noticed in smooth muscle tumors and leiomyosarcomas, two other types of uterine cancer. The identification of MED12 mutations as the sole genetic abnormality originates in leiomyomas raises the opportunity of a role in the genesis of cancer. 10% - 15% of women who are of reproductive age have endometriosis, which grants serious difficulties because of its chronic nature and range of clinical symptoms. Even after effective surgeries, issues reoccur often, adding to the enormous financial burden. The effects of MED12 mutations have been experiential in recent studies examining the molecular causes of endometriosis-associated infertility, which have shown anomalies in cellular connections and signaling cascades. Computational techniques were used in this study to investigate LifeGreenTM’s potential to prevent uterine fibroids and breast cancer. The efficacy of LifeGreenTM as a preventive measure or a treatment for common gynecological matters was examined and modeled. We investigated the mechanisms underlying LifeGreenTM’s benefits in the treatment of uterine fibroids and breast cancer using computational techniques. Our research contributes to our understanding of its potential therapeutic benefits for women’s health.

Based on network pharmacology,molecular docking and experimental validation to reveal the potential molecular mechanism of quercetin for the treatment of diarrheal irritable bowel syndrome

Objective:To explore the potential mechanism of action of quercetin in the treatment of diarrhea irritable bowel syndrome(IBS-D).Methods:The potential targets of quercetin were obtained from the TCMSP,SwissTar-getPrediction,and BATMAN-TCM databases.The targets of IBS-D were obtained by searching the GeneCards database with"diarrhea irritable bowel syndrome"as the keyword,and the targets of quercetin and IBS-D were intersected.The PPI network was constructed by Cytoscape 3.7.1 software.The intersected targets were imported into the DAVID database for GO functional analysis and KEGG pathway enrichment analysis.The binding ability of quercetin to the core targets was observed using molecular docking.Based on this,we established an IBS-D rat model,administered quercetin for intervention,and experimentally validated the network pharmacology prediction results by HE staining and ELISA assay.Results:Network pharmacology analysis showed that TP53,TNF-α,AKT1,VEGF-A,IL-6 factors and MAPK,PI3K-Akt signaling pathway as the core targets and pathways of quercetin for the treatment of IBS-D.The results of animal experiments revealed that quercetin could inhibit the secretion of TP53,TNF-α,AKT1,VEGF-A,IL-1βand IL-6,reduce the inflammatory response and improve IBS-D.Conclusion:Quercetin could protect colon tissue by regulating the expression of TP53,TNF-α,AKT1,VEGF-A,IL-1βand IL-6,thereby treating IBS-D.

Investigating the molecular mechanism of Chelidonii Herba against liver cancer using network pharmacology and molecular docking validation

Background:The molecular mechanism of Chelidonii Herba in treating hepatocellular carcinoma was investigated using network pharmacology and molecular docking validation.Methods:The main active components of Chelidonii Herba were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database,and the targets of these active ingredients were identified using the SwissTargetPrediction platform.Targets related to liver cancer were sourced from GeneCards,Therapeutic Targets Database,and Online Mendelian Inheritance in Man databases.Intersection targets between the active components of Chelidonii Herba and liver cancer were determined using the jvenn online platform.The protein interaction network was analyzed via STRING database and visualized using Cytoscape 3.9.1.Core targets were identified and further analyzed within the protein interaction network.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted for the intersection targets using the DAVID database to correlate gene functions.Sankey bubble diagrams for Gene Ontology enrichment analysis and circular diagrams for Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were generated using CNSknowall and SangerBox online platforms.Molecular docking and visualization were performed using AutoDockTools 1.5.7 and PyMOL 2.5.7 software,respectively.Overall survival and pan-cancer analysis of core targets were conducted using the GEPIA2 online platform.Results:Twelve active components of Chelidonii Herba were identified through screening.A total of 103 intersection targets and 12 core targets were found between these active constituents of Chelidonii Herba and liver cancer.Chelidonii Herba may exert its effects on liver cancer through these 12 core targets.Several signaling pathways are implicated,including chemical carcinogen-receptor activation,endocrine resistance,HIF-1 signaling pathway,and proteoglycans in cancer.Conclusion:Chelidonii Herba potentially intervenes in cancer-related signaling pathways for treating liver cancer by targeting AKT1,EGFR,and ERBB2.This action is facilitated by active ingredients such as(S)-chrysocorydaline,dihydrochelidonorubin,cryptopine,and oxysanguinarine.Chelidonii Herba may address liver cancer through a mechanism involving multiple components,targets,and pathways.

Exploring the molecular mechanism of Baoyuan decoction in the treatment of lung cancer based on network pharmacology and molecular docking

Background:Baoyuan decoction is used clinically as an adjuvant treatment for lung cancer.However,the underlying mechanism remains unclear.Therefore,this study aimed to explore the mechanism of action of Baoyuan decoction in lung cancer treatment using network pharmacology and molecular docking technology.Methods:The Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction databases were used to screen the active ingredients of Baoyuan decoction and their relevant targets.Lung cancer-related targets were obtained from the GeneCards,Online Mendelian Inheritance in Man,and DrugBank databases.Protein-protein interaction network of the common targets was constructed using the STRING database and analyzed using Cytoscape software 3.10.1.Furthermore,Gene Ontology enrichment,Kyoto Encyclopedia of Genes and Genomes pathway analyses and visualization of common genes were performed using the R software.Finally,molecular docking of the selected key ingredients and targets was performed,and the results were verified using AutoDock Vina software.Results:We identified 142 potential active ingredients,3624 potential lung cancer-related targets,and 341 common drug targets.A total of 72 core targets were identified,of which AKT1,TP53,interleukin-6,epithelial growth factor receptor,and signal transducer and activator of transcription 3 were key.A total of 4116 items were obtained via Gene Ontology enrichment analyses.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 189 related signaling pathways,including the PI3K-Akt,AGE-RAGE signaling pathways in diabetic complications,FOXO,and TH signaling pathways,which are involved in cell proliferation,autophagy,metastasis,invasion,radiation resistance,and chemotherapy resistance in the lung cancer microenvironment.The molecular docking results suggested that the key ingredients had a strong affinity for key targets.Conclusion:This study demonstrates that Baoyuan decoction plays a key therapeutic role in a complex manner involving multiple ingredients,targets,and pathways in lung cancer.Our findings are anticipated to provide new ideas for follow-up experimental research and clinical application.

Therapeutic Effects and Potential Mechanisms of Glyasperin A against Myocardial Ischemia Based on Network Pharmacology and Molecular Docking

[Objectives]To explore the therapeutic effects and potential mechanisms of Glyasperin A(GAA)on myocardial ischemia(MI)based on network pharmacology and molecular docking.[Methods]The molecular structure of GAA was downloaded from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and all targets of GAA were predicted by converting 3D model molecules into SMILES online tool and Swiss target prediction.Genecards database and DisGeNET database were used to find the targets related to MI,and then Venny 2.1.0 was used to generate the corresponding Wayne diagram,and then Cytoscape 3.9.1 software was used to construct the protein-protein interaction(PPI)network.With the help of DAVID database and Microbiology,the selected core targets were enriched and analyzed by gene ontology(GO),biological process(BP),and Kyoto Encyclopedia of Genes and Genomes(KEGG),and then the molecular docking between GAA and core targets was verified by AutoDock and Pymol software.[Results]A total of 1883 MI targets were screened,and in the protein-protein interaction network,AKT1,PTGS2,PPARG,ESR1,GSK3B were the proteins with higher values.Gene ontology and KEEG enrichment analysis showed that the biological processes involved mainly included inflammatory response,negative regulation of gene expression,and response to exogenous stimuli.Signaling pathways mainly include IL-17 signaling pathway,HIF-1 signaling pathway,and so on.The results of molecular docking showed that the binding energy of GAA and core protein was less than-5 Kcal/mol in four groups.These indicated that GAA with good binding had a certain therapeutic effect on myocardial ischemia.[Conclusions]Based on the systematic network pharmacology method,this study predicts the basic pharmacological effects and potential mechanisms of GAA in the treatment of MI,and reveals that GAA may treat MI through multiple targets and signaling pathways.It is expected to provide a basis for further study of its pharmacological mechanisms.

Effects of ginkgo flavone aglycone on atherosclerosis based on network pharmacology,molecular docking,and in vitro experiments

Background:Ginkgo flavone aglycones(GA),a Ginkgo(Ginkgo biloba)extract,has been proven to have good biological activity in atherosclerosis(AS)treatment.Moreover,its active compounds and the corresponding mechanism for the treatment of AS remain unclear.Methods:To evaluate and identify the potential pharmacological mechanisms of GA in AS treatment,the program Cytoscape was used to generate network mappings of the GA-AS-potential target gene.GO and KEGG enrichment analyses were performed to further investigate the potential mechanism of AS and the pharmacological properties of GA.A molecular docking approach was utilized to determine the GA components that interact with Akt.In vitro experiments were carried out to identify the anti-atherosclerotic effects of GA by targeting Akt.Results:Network pharmacological research determined that the active components of GA(quercetin,kaempferol,and isorhamnetin)correlated with AS target genes such as AKT1,EGFR,SRC,ESR1,PTGS2,MMP9,KDR,GSK3B,APP,and MMP2,respectively.GO enrichment and KEGG analysis showed that PI3K-Akt signaling may play an important role in GA treatment.Molecular docking experiments indicated that quercetin,kaempferol,and isorhamnetin integrate into the binding pockets of the most potentially beneficial GA-AS target protein(Akt).Consequently,cell experiments were conducted to support the anti-atherosclerotic activity of GA on AS by inhibiting the phosphorylation of AKT1 and its downstream signaling molecules,which regulated the proliferation of HASMCs.Conclusion:Our results detailed GA's active ingredients,potential targets,and molecular basis against AS.GA may exert anti-atherosclerotic effects by suppressing Akt phosphorylation and inhibiting the proliferation of HASMCs.It also proposed a viable approach to determining the scientific foundation and therapeutic mechanism of Chinese herbal medicine extracts in disease therapy.

Exploring the effect and mechanisms of Epimedium on diabetic testicular injury using network pharmacology,molecular docking,and cell experiments

Background:Studying the potential targets and mechanisms of Epimedium for anti-diabetic testicular injury using network pharmacology,molecular docking,and cell experiments.Methods:Acquisition of major components and targets of Epimedium was based on TCMSP,TCMID,and Symmap databases and retrieval of diabetic testicular injury targets by OMIM,GeneCards,Pharmgkb,and Drugbank databases.Intersecting targets were obtained from the Venny 2.1.0 database and input SRTING data to construct a protein-protein interaction(PPI)network,and key targets were screened in Cytoscape 3.8.0 software.Then the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of intersecting targets were conducted through the DAVID database.Further,AutoDock software was used to verify docking between the main components and the core target proteins.In addition,a Cell Counting Kit-8(CCK-8)assay was used to determine the survival effect of quercetin,the main component of Epimedium,on TM4 sertoli-like cells exposed to palmitic acid(PA).Results:Quercetin,kaempferol and luteolin in epimedium were identified as the main components in the treatment of diabetic testicular injury.It has core target proteins including MMP9,AKT1,and TNF.The biological process mainly involves the regulation of the apoptotic signaling pathway.The key pathways of KEGG are the AGE-RAGE signaling pathway in diabetic complications,PI3K-Akt and MAPK signaling pathway.Molecular docking results showed that quercetin had the strongest binding ability to MMP9.Also,PA-challenged cells had a lower survival rate,which was alleviated by the administration of quercetin.Conclusion:Our findings suggest that Epimedium attenuates diabetes mellitus(DM)-induced testicular injury through AGE-RAGE,PI3K-Akt and MAPK signaling pathway.These insights offer a potential therapeutic strategy for managing DM-induced testicular injury,will be the basis for future clinical research.

Predicting bioactive compounds and cancer-related molecular targets of lotus seedpod (Receptaculum Nelumbinis) based on network pharmacology and molecular docking

Background:Lotus seedpod(Receptaculum Nelumbinis)is the abundant by-products produced during lotus seed processing,and the sources are usually considered to be wastes and are abandoned outdoors or incinerated.This study aims at predicting its bioactive compounds and cancer-related molecular targets against six cancers,including lung cancer,gastric cancer,liver cancer,breast cancer,ovarian cancer and cervical cancer.Methods:Network pharmacology and molecular docking methods were performed.Results:Network pharmacology results indicated that 14 core compounds(liensinine,tetrandrine,lysicamine,tricin,sanleng acid,cireneol G,ricinoleic acid,linolenic acid,5,7-dihydroxycoumarin,apigenin,luteolin,morin,quercetin and isorhamnetin)and 10 core targets(AKT1,ESR1,HSP90AA1,JUN,MAPK1,MAPK3,PIK3CA,PIK3R1,SRC and STAT3)were screened for lotus seedpod against the six cancers.Molecular docking analysis suggested that the binding abilities between the core compounds and the core targets were mostly strong.GO analysis revealed that the intersected targets between the bioactive compounds of lotus seedpod and the six cancers were significantly related to biological processes,cell compositions and molecular functions.KEGG analysis showed that PI3K-Akt,TNF,Ras,MAPK,HIF-1 and C-type lectin receptor signaling pathways were notably involved in the anti-cancer activities of lotus seedpod against the six cancers.Conclusions:14 core compounds and 10 core targets were screened for lotus seedpod against lung cancer,gastric cancer,liver cancer,breast cancer,ovarian cancer and cervical cancer.This study supports the application of lotus seedpod in treating cancers,and promotes the recycling and the high-value utilization.