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.

FitDockApp:基于模板的分子对接PyMOL插件图形化计算软件

目的分子对接在预测分子之间的结合模式和亲和力方面起着至关重要的作用,是计算结构生物学和计算机辅助药物设计研究的重要方法。本研究团队近期开发了一款基于模板的新型对接方法FitDock,当存在近似的蛋白质配体模板时,它在准确性和速度方面都超过了业界常用的分子对接方法。为了增强FitDock方法的可用性,使其在分子模拟领域得到更广泛的应用,很有必要发展图像化的软件工具。方法基于Python图像化编程,本文开发了FitDockApp,这是分子可视化软件PyMOL的插件软件。结果FitDockApp能够通过操作窗口界面,实现基于模板的分子对接和配体结构比对,实时显示预测三维结构,并提供将对接文件上传到实验室服务器获取最优模板的便利。此外,FitDockApp还具备批量对接功能。结论FitDockApp通过用户友好的界面简化了对接过程,并提供丰富的功能,帮助研究人员获得精确的对接结果。FitDockApp是一款免费软件,兼容Windows和Linux系统,可在http://cao.labshare.cn/fitdock/下载。

A guidance strategy for rendezvous and docking to the space station in the Earth-Moon NRHO orbit

With the development of space technology,it is possible to build a space station in Earth-Moon space as a transit for Earth-Moon round-trip and entering in the deep space.Rendezvous and docking is one of the key technologies for building an Earth-Moon space station.A guidance strategy for rendezvous and docking from the Earth orbit to the space station in the Earth-Moon NRHO orbit is proposed in this paper,which is suitable for engineering applications.Firstly,the rendezvous and docking process is divided into three sections,i.e.,the large-range orbit transfer section,far-range guidance section,and close-range approaching section.The suitable terminal of large-range orbit transfer is selected according to the eigenvalue of NRHO orbit state transition matrix.The two-impulse guidance method based on the relative motion equation in the three-body problem is adopted for the far-range guidance section.The impulse time and amplitude are solved with the optimization algorithm.The linear constant three-body relative motion equation is proposed for the close-range approaching section,and the rendezvous and docking is completed by a two-stage linear approximation.Finally,a simulation analysis is carried out,and the simulation results show that the adopted dynamics equations and the designed guidance law are effective,and the three flight phases are naturally connected to accomplish the rendezvous and docking mission from the Earth orbit to the space station on the Earth-Moon NRHO.

Curcumin for gastric cancer:Mechanism prediction via network pharmacology,docking,and in vitro experiments

BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.AIM To elucidate the potential mechanisms of curcumin in the treatment of GC.METHODS Network pharmacological approaches were used to perform network analysis of Curcumin.We first analyzed Lipinski’s Rule of Five for the use of Curcumin.Curcumin latent targets were predicted using the PharmMapper,SwissTargetPrediction and DrugBank network databases.GC disease targets were mined through the GeneCard,OMIM,DrugBank and TTD network databases.Then,GO enrichment,KEGG enrichment,protein-protein interaction(PPI),and overall survival analyses were performed.The results were further verified through molecular docking,differential expression analysis and cell experiments.RESULTS We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets.The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways.Following PPI analysis,6 hub targets were identified,namely,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),cytochrome P450 family 3 subfamily A member 4(CYP3A4),mitogen-activated protein kinase 14(MAPK-14),cytochrome P450 family 1 subfamily A member 2(CYP1A2),and cytochrome p450 family 2 subfamily B member 6(CYP2B6).These factors are correlated with decreased survival rates among patients diagnosed with GC.Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes.The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation.mRNA levels of hub targets CYP3A4,MAPK14,CYP1A2,and CYP2B6 in BGC-823 cells were significantly increased in each dose group.CONCLUSION Curcumin can play an anti-GC role through a variety of targets,pathways and biological processes.

Antioxidant and lipoxygenase inhibitory properties of a novel flavonoid from Pistacia chinensis Bunge and its molecular docking analysis

Background:Pistacia chinensis Bunge has been traditionally used to manage various conditions,including asthma,pain,inflammation,hepatoprotection,and diabetes.The study was conducted to investigate the antioxidant and anti-lipoxygenase(LOX)properties of the isolated compound 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one from Pistacia chinensis.Methods:LOX assay and antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl(DPPH)assay were performed.Molecular docking studies were conducted using a molecular operating environment.Results:The LOX assay revealed significant inhibitory effects at 0.2µM concentration,with an IC50 value of 37.80µM.The antioxidant effect demonstrated dose-dependency across 5 to 100µg/mL concentrations,reaching 93.09%at 100µg/mL,comparable to ascorbic acid’s 95.43%effect.Molecular docking studies highlighted strong interactions with the lipoxygenase enzyme,presenting an excellent docking score of-10.98 kcal/mol.Conclusion:These findings provide valuable insights into Pistacia chinensis’chemical components and biological effects,reinforcing its traditional medicinal applications.

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 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.

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 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.

Docking of Human Band 3 Anion Transporter Proteins with Their Plasmodium falciparum Interactors Based on Short Linear Motifs

Plasmodium (P.) falciparum is a pathogen that causes severe forms of malaria. Protein interactions have been shown to occur between P. falciparum and human erythrocytes in human blood. The Band 3 Anion Transporter (B3AT) protein is considered the main invasive pathway for the parasite in erythrocytes that causes clinical symptoms for malaria in humans. The interactions between P. falciparum parasites and erythrocytes along this receptor have previously been explored. Short linear motifs (SLIMs) are short linear mediator sequences that involve several biological processes, acting as mediators of protein interactions identifiable by computational tools such as SLiMFinder. For a given protein, the identification of SLIMs allows predicting its interactors. Using the SLIMs approach, protein-protein interaction network analyses between P. falciparum and its human host, were used to identify a tryptophan-rich protein, A5K5E5_PLAVS as an essential interactor of B3AT. To better understand the interaction mechanism, a guided protein-protein docking approach based on SLIM motifs was performed for human B3AT and A5K5E5_PLAVS. The highlights of this important interaction between P. falciparum and its human host have the potential to pave the way to identify new therapeutic candidates.

Study on the interaction between volatile oil components and skin lipids based on molecular docking techniques

Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules;and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers.Methods In this study;210 different structural types of VOCs were selected from the VOCMM penetration enhancer database;and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2);cholesterol(CHL);and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control;Nootkatone;and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments;with three rats in each group.The donor pool solutions were 3%gastrodin;3%gas-trodin+3%nootkatone;and 3%gastrodin+3%3-butylidenephthalide;respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12;µg/cm²).Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA;and hydrogen bonded to the head group of CER2.Among them;sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings;benzene rings;and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis;most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09µg/cm2;and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5503.00±1080.00µg/cm²;P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98µg/cm²;P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2.Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers;and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.

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.

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.

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.

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 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.

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.

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 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.

Mechanism of Polygoni Cuspidati Rhizoma in treating atherosclerosis based on network pharmacology and molecular docking

Background:The incidence and prevalence of atherosclerosis(AS)is increasing every year and has becoming a major health issue of global concern.Polygoni Cuspidati Rhizoma(PCR)is a Chinese herb that is widely used clinically for the treating of AS.However,its pertinent targets and probable mechanisms,still need to be completely explored.Methods:Active compounds and targets for PCR and AS targets were screened using public databases.A“drug-component-disease target”network map was created and analyzed after using the Venn online tool to identify common targets and Cytoscape software to screen drug-disease core targets.Critical targets pathway enrichment analyses are conducted using the Metascape database.Using AutoDock Vina and Pymol software,docking validation and visualization of active components and core targets were carried out.Results:PCR was obtained for ten compounds with 105 AS-related targets.Rhein,quercetin,beta-sitosterol,and luteolin may be drug candidates,and the genes for AKT1,TNF,IL-6,EGFR,TP53,IL-1,RELA,and VEGFA are potential therapeutic targets,according to network analysis.PCR might modulate the AGE/RAGE,PI3K/Akt,IL-17 and NF-ᴋB signaling pathways against the development of AS.Molecular docking indicated that quercetin has high affinity for AKT1 and TNF gene targets.Conclusion:This study provides rare information and scientific basis for further exploration of PC in the treatment of AS.