The mechanism of Callistephus chinensis flavonoid compounds in the treatment of diabetes using network pharmacology and molecular docking

The purpose of this project is used for exploring the mechanism of Callistephus chinensis in the treatment of diabetes by network pharmacology and molecular docking methods.The target of Callistephus chinensis was obtained from SwissTargetPrediction database,while the target related to diabetes was obtained from GeneCards and OMIM databases.The target was added in String database to build the protein interaction network.GO biological process enrichment analysis and KEGG pathway enrichment analysis were carried out by Metascape software,then the target-pathway network was constructed.Molecular docking was carried out in Discovery Studio 2016 Client software to verify the binding force of Callistephus chinensis flavonoid compounds with key targets.In this study,10 potential active components were selected from the flavonoid monomer compounds of Callistephus chinensis.1847 biological processes(BP),126 cell compositions(CC)and 256 molecular functions(MF)were obtained by GO enrichment analysis;a total of 194 pathways were involved in KEGG enrichment analysis of 192 cross targets.Network analysis showed that quercetin was the main active component of flavonoids in the treatment of diabetes,AKT1,TNF,VEGFA,EGFR,SRC and other related signals were in relation to the treatment of diabetes.This study showed that Callistephus chinensis flavonoid compounds play a role in the treatment of diabetes by regulating multi-target and multi-pathway.

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.

Mechanism of action of Balanophora involucrata polyphenolic compounds in the treatment of myocardial injury based on network pharmacology and molecular docking techniques

The objective of this work was to investigate the mechanism of action of Balanophora involucrata polyphenolic compounds in the treatment of myocardial injury.In the present study,Balanophora involucrata was extracted by refluxing 75%of ethanol.The obtained extract was extracted with petroleum ether,ethyl acetate and n-butanol respectively.And the ethyl acetate layer was separated.The extract was prepared by silica gel column chromatography,sephadex LH-20 elution and thin layer chromatography.After that,the Swiss target prediction database was utilized to obtain the targets of Balanophora involucrata,and the Genecards,OMIM and TTD databases were used to predict and screen the targets of Balanophora involucrata for the treatment of myocardial injury.The active ingredient-target network was constructed using Cytoscape software,and the PPI network was mapped using String database and Cytoscape software.GO bioprocess enrichment analysis and KEGG pathway enrichment analysis were performed by Metascape software to predict the mechanism of action.Molecular docking was performed in Discovery Studio 2016 client software to verify the binding of Balanophora involucrata polyphenols to key targets.In this study,six polyphenolic compounds were isolated from Balanophora involucrata.By GO enrichment analysis,1614 biological processes(BP),127 cellular compositions(CC),and 215 molecular functions(MF)were obtained;a total of 155 cross-targets were involved in the KEGG enrichment analysis.The PPI network showed that quercetin was the main active component of polyphenolic compounds against myocardial injury and that AKT1,EGFR,STAT3,SRC,ESR1,MMP9,HSP90AA1 and other related signals were associated with myocardial injury treatment.Finally,the multi-component-multi-target-multi-pathway action of Balanophora involucrata was concluded,which provided new ideas and methods for further research on the mechanism of action of Balanophora involucrata in myocardial injury.

Molecular mechanism of Compound Qingdai Capsule in the treatment of psoriasis based on network pharmacology and molecular docking

Objective:Although Compound Qingdai Capsule(CQC)successfully treats psoriasis,the exact mechanism remains unclear.Our research used network pharmacology to investigate the molecular mechanism of CQC in treating psoriasis.Methods:The Traditional Chinese Medicine Systems Pharmacology platform was used to screen the bioactive chemical elements and identify gene targets,and the ingredient-target network was visualized by Cytoscape software.Genes associated with psoriasis were found in the Gene Expression Omnibus database.The protein-protein interaction network was created using STRING and Cytoscape,and the hub genes were identified using MCODE and topological analysis.Gene ontology and Kyoto encyclopedia of genes and genomes analyses were applied to obtain hub genes’biological processes and signaling pathways.Subsequently,the ingredient-target-pathway-disease network was visualized by Cytoscape.Results:Finally,an active ingredient-target network of CQC containing 130 active ingredients and 213 targets was built.Conclusion:The top 3 bioactive components were identified as quercetin,luteolin,and kaempferol,and the top 5 hub genes were identified as IL1B,CXCL8,STAT3,MMP9,and HMOX1.The critical pathways of CQC treatment in psoriasis were AGE-RAGE signaling,IL-17 signaling,TNF signaling,Fluid shear stress and atherosclerosis,and Toll-like receptor signaling pathway.Molecular docking confirmed a robust binding affinity between the main active ingredients of CQC with the hub target proteins.On this basis,additional animal or cellular research might be undertaken to investigate the targets and mechanisms of CQC treatment in psoriasis.

Research progress of modern pharmacological effects of Pueraria lobata and its compound clinical application

As a traditional Chinese medicine, Pueraria lobata has been widely recorded in Chinese herbal works of the past dynasties. Modern studies have found that its main chemical components are isoflavones, triterpenoids, saponins, etc., which have antipyretic, anti⁃inflammatory, anti⁃infection, blood pressure, blood sugar, blood lipid, and pharmacological effects such as improving reproductive function. Clinically, it is used in the treatment of diabetic diseases, gastrointestinal diseases, cardiovascular diseases, etc. in the form of traditional Chinese medicine compound prescriptions. This reseach aims to summarize related articles of Pueraria lobata in the past 5 years, focusing on its pharmacological effects and clinical application of the compound, and provide references for its further development and utilization.

A network pharmacology approach to explore the mechanism of action of Yiqi Fumai lyophilized injection in the treatment of novel coronavirus disease

Background:Shengmai decoction,which has been included in the diagnosis and treatment of coronavirus disease 2019(COVID-19),is effective in the early treatment of patients with severe COVID-19.Yiqi Fumai lyophilized injection(YQFM)is a modern Chinese medicine preparation of the Shengmai decoction.The mechanism of its intervention at the molecular level in the severe stage of COVID-19 remains unclear.Therefore,it is necessary to investigate the mechanism of YQFM in the treatment of patients with severe COVID-19.Methods:The corresponding target genes of the main active ingredients in YQFM and COVID-19 were obtained by using multiple databases and literature retrieval.A protein-protein interaction network was constructed,and enrichment analysis of the target was performed using Cytoscape 3.8.1.Lastly,the docking of all the identified compounds with angiotensin-converting enzyme II was confirmed by applying molecular docking technology.Results:YQFM has anti-inflammatory effects on RAW267.4 macrophages.The main active compounds of YQFM are all effective anti-inflammatory agents,and these active compounds also show beneficial physiological functions,such as anti-oxidation,anti-bacterial,and anticancer activities.Gene Ontology analysis showed enrichment in the following pathways:lipopolysaccharides,interleukins,NF-kappa B,interleukin-2 and others,revealing that YQFM may play a role in the treatment of patients with severe COVID-19 through these pathways.Conclusion:YQFM has multicomponent and multitarget characteristics,and it could reduce lung injury by inhibiting inflammatory reactions,promoting antiviral activities,and regulating immunity,among other functions,to treat patients with severe COVID-19.

Target Prediction and Molecular Mechanism of Compound Honggencao for Upper Respiratory Tract Infection Based on Network Pharmacology

Objective: The target prediction and molecular mechanism of compound Honggencao in the treatment of upper respiratory tract infection were investigated based on network pharmacology. Methods: In the database of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, chemical composition and potential targets of compound Honggencao were mined, and the target gene of upper respiratory tract infection of compound Honggencao was extracted from GeneCards databases. The protein-protein interaction of target genes was constructed. Then, the essential genes of enrichment of KEGG pathway analysis and functional analysis were analysed. Results: Compound Honggencao had 69 kinds of active ingredients. The upper respiratory tract infection of the target gene was 186 that built compound Honggencao on the relationship between upper respiratory tract infections of protein interaction networks, which had a total of 186 nodes, 3515 sides. Fifty-six essential genes were including IL-17, EGFR and CDND1, and so on. Gene ontology analysis had 2567 items, and pathway analysis was 166 items. The main signaling pathways involved with IL-17 signaling pathways, tumour necrosis factor signal pathway and human cytomegalovirus infection, and so on. Conclusion: The pharmacological action of compound Honggencao on upper respiratory tract infection was characterized by the synergistic effect of multiple components and multiple targets, which provided an absolute theoretical basis for the research on the pharmacological direction of molecular signaling pathway and a specific theoretical basis for clinical use.

Exploring the mechanism of hypolipidemic effect of polyphenols in wolfberry based on network pharmacology and molecular docking

To explore the mechanism of hypolipidemic action of wolfberry polyphenols by using network pharmacology and molecular docking.The active ingredients and targets of wolfberry were searched by TCMSP,and the Cytoscape 3.9.0 software was used to construct a“wolfberry component-target”network.The Gene Cards database was used to screen the hyperlipidemic targets and intersect them with the active targets of wolfberry to construct the PPI network using the STRING platform.The gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of the core targets were carried out on the Metascape platform,and molecular docking of the active ingredients to the core targets was performed using AutoDockTools software.A total of 33 active ingredients and 173 potential targets of wolfberry were screened,including 99 targets related to hyperlipidemia.The results of the analysis of 99 intersecting targets with the components of wolfberry identified the core active ingredients as quercetin,glycitein and atropine.The binding of the major components of wolfberry,including the polyphenolic compounds quercetin and glycitein,as well as atropine to the key targets AKT1,IL6 and TNF may be important mechanisms for the hypolipidemic therapeutic effect.GO functional enrichment analysis involves biological processes,cellular components,and molecular functions.The KEGG pathway enrichment analysis mainly involves the AGE-RAGE signaling pathway,fluid shear stress,and TNF signaling pathway.Molecular docking validated the good binding activity of the targets to the active ingredients.The binding of atropine and the polyphenolic compounds quercetin and glycitein to the key targets AKT1,IL6 and TNF may be an important mechanism for the hypolipidemic therapeutic effect of wolfberry.

Network pharmacology based method for mechanistic investigation of the Compound Xintahua in the treatment of atherosclerosis

目的:本研究采用网络药理学技术,从分子水平深入探讨复方新塔花抗动脉粥样硬化的作用机制。方法:利用TCMSP数据库和文献挖掘技术对复方新塔花中的主要活性成分进行筛选,通过Swiss TargetPrediction数据库进行主要活性成分的靶点预测分析。将目标靶点导入FunRich数据库进行靶点注释与分析,最后结合FunRich数据库进行通路分析,确定复方新塔花的作用机制。结果:共筛选得到316个化合物、117个靶点、290条信号通路,其中有16个活性成分、39个目标靶点、43条主要信号通路与动脉粥样硬化有关。结论:研究结果表明,复方新塔花黄酮类、酚类、有机酸、萜类成分可能通过参与调节脂质代谢,血管生成、氧化反应、炎症反应、内分泌代谢、细胞增殖与凋亡等过程,从而多成分、多靶点、多通路协同发挥抗动脉粥样硬化的作用。

Research Progress in the Application of Network Pharmacology in Traditional Chinese Medicine and Compound Prescriptions

Network pharmacology is a new discipline based on the theory of systems biology,mainly for network analysis of biological systems.It selects specific signal nodes for multi-target drug molecular design.This article summarizes the application of network pharmacology in traditional Chinese medicine and compound prescriptions in recent years from the research progress of network pharmacology,the current research status of single herbs,and the research and application of compound prescriptions.

Preliminary exploration of the mechanism of compound Qinlan oral liquid against new coronavirus pneumonia based on network pharmacology and molecular docking technology

Objective:Applying Traditional Chinese Medicine(TCM)network pharmacology and molecular docking technology to explore the mechanism of anti-coronary virus pneumonia(Corona Virus Disease 2019,COVID-19)of Compound Qinlan oral liquid.Methods:Traditional Chinese Medicines Integrated Database(TCMID),Traditional Chinese Medicine Systems Pharmacology(TCMSP),OMIM,GeneCards,String and others online databases were used for building a series of networks,and selecting the core targets and analyzing the signal pathways.Finally,Discovery Studio 2016 software was used to conduct molecular docking of the main compounds(Chinese Medicine Legal Quality Control Compound)of Compound Qinlan oral liquid with key targets ACE2,3CLpro,etc.Results:the results showed that Compound Qinlan oral liquid has specific effects in lung,heart and stomach diseases.The Compound Qinlan oral liquid compound-pneumonia target network contained 98 compounds and 184 corresponding targets,and the core targets involved INS,TP53,IL6,VEGFA,ALB and JUN.GO(GeneOntology)function enrichment analysis yielded 653 GO entries,and KEGG(KyotoEncyclopedia of Genes and Genomes)enrichment screening yielded 112 related pathways,including hypoxia inducible factor-1(HIF-1)and Toll-like receptor(TLRs)signaling pathway related to pneumonia,as well as Influenza A signaling pathway and Hepatitis B signaling pathway related to microbial infection.The results of molecular docking show that Isochlorogenic acid C,Baicalein,etc have good binding capacity with ACE2,3CLpro,AKT1 and other proteins.Conclusion:In this paper,we preliminarily explored the potential therapeutic mechanism for Compound Qinlan oral liquid to against coronavirus pneumonia(COVID-19)and predicted the active ingredients.We hope that the results will help to further study on the active ingredients and mechanism of Compound Qinlan oral liquid for anti-COVID-19.

Analyzing the effective compounds, potential targets and diseases of Jianpi Jiedu recipe based on network pharmacology and function validation of cytobiology

Objective: To analyze the active compounds, potential drug targets and therapy diseases of Jianpi Jiedu Recipe (JPJDR) based on network pharmacology and bioinformatics technology, and verify the biological function of some active compounds by cytology experiments. Methods: The online databases including TCMSP, TCMID, Cancer HSP, TCM-PTD, TCM Database@Taiwan and DrugBank were applied to screen the active compounds and the potential drug targets of JPJDR. Cytoscape 3.3 software was executed to construct the network between active compounds and drug targets. DAVID database was used to probe the effective diseases and analyze the involved KEGG pathways according to the predicted targets corresponding to JPJDR. Results: According to the rules of oral bioavailability (OB)>30% and drug-likeness (DL)>0.18, 58 of 513 effective compounds in JPJDR were screened out, as well as the corresponding 437 potential drug targets. By the analysis of DAVID database, all these key targets were associated closely with the occurrence and development of metabolic disorders and cancers, and all the targets were closely correlated with the pathways in cancer. Further analysis demonstrated that, there were a lot of effective compounds in JPJDR, such as Quercetin, Formononetin, Stigmasterol, Diosgenin,β-sitsterol, Oxymatrine, Kaempferol, Isorhamnetin and Ampelopsis. The results of cell proliferation experiments further showed that, among the selected nine key traditional Chinese medicine compounds, only Ampelopsis can dose-dependently inhibit the proliferation of colorectal cancer cells. Conclusions: Through network pharmacology analysis, we found that JPJDR contains many effective compounds which may directly target to the cancer-related proteins. 9 compounds were the major active compounds with high degrees of targets. Among the 9 screened compounds, Ampelopsis was validated for its inhibitory effect on the proliferation of colorectal cancer cells using CCK-8 assay. Network pharmacology is an effective approach to explore the functional mechanism of formula.

Network pharmacology-based analysis on bioactive compounds and mechanisms in Yiqifumai formula in the treatment of heart failure

Objective To predict the main bioactive components and potential mechanisms of Yiqifumai formula on heart failure by network pharmacology.Methods The bioactive compounds of Yiqifumai formula were screened by TCMSP database.The target genes of heart failure were obtained by entering PharmMapper and GeneCards database.R 3.6.3 was used to intercept intersection network for candidate targets.The network of“drug-compound-target-disease”was established via Cytoscape 3.7.2 and STRING platform.The DAVID database was used for GO enrichment analysis and KEGG pathway based on the candidate targets.Results Eleven key compounds(such as Schizandrin C,Gomisin G,ginsenoside rh2,Ruscogenin etc.,),426 non-repeated targets and 382 heart failure targets were obtained from Yiqifumai formula.There were 565 GO items(P<0.05),among which 412 were biological process(BP)items,63 were cell components(CC)items,and 93 were molecular function(MF)items.One hundred and seventeen signal pathways were enriched by KEGG pathway(P<0.05).Conclusion The bioactive compounds in Yiqifumai formula can play the“multi-target”role of enhancing resistance and eliminating pathogenic factors via regulation of angiogenesis and immune in the treatment of heart failure.

Study on pharmacodynamic mechanism of compound Shuanghuanglian in prevention and treatment of pneumonia based on network pharmacology and association analysis

Background:Platform for prediction and analysis of Chinese medicine against coronavirus disease 2019(TCMAntiCOVID-19 V1.0)was used to explore the active ingredients,key targets and mechanisms of the compound coronavirus disease 2019(COVID-19),It will provide a reference for the clinical application of this prescription as a broad-spectrum agent in the prevention and treatment of pneumonia.It will also win valuable time for finding symptomatic Chinese medicine prescriptions and vaccine research and development.Methods:Set Banxia Tianma Baizhu decoction as the negative control.Qingfei Paidu decoction as the positive control,and use TCMAntiCOVID-19 V1.0 platform to predict the potential efficacy of compound Shuanghuanglian.We used the quantitative evaluation algorithm of multi-target drugs for the network disturbance of disease,by comparing the changes of network topological characteristics before and after drug intervention,and using the disturbance rate to evaluate the drug’s dryness for disease prediction.Using batman-TCM,the credibility card value of the target sets 20,then the target of traditional Chinese medicine composition is predicted,the heterogeneous network of traditional Chinese medicine composition-drug target-disease target is established.The interaction of related network is realized by JavaScript Visualization is realized,and cycloscape is edited.The average connectivity,the average shortest path length,the centrality of connectivity and the centrality of network compactness are calculated by using R’s iGraph package,and nulldistribution is used as the overall distribution to correct the disturbance rate of drugs to the real network,so as to evaluate the stability of network topology and explore its mechanism.Results:The key targets of COVID-19 were Aif1,Ccl2,Cdc20,Cxcl13,Fcer1g,Ido1,Ifng,Il10,Il1rnIl6,Ncf4,Ptger4,Spi1,Tnf,Xcl1;after the intervention,the average connectivity,the average shortest path length,the network connectivity centrality and the network tightness centrality were(2.31e+1),(2.41e+0),(6.21e−1),(1.68e−2)respectively;the total scores of network stability evaluation of drug intervention diseases were 18.29,12.59 and 19.10 respectively.Conclusion:Compound Shuanghuanglian can effectively break the stability of the disease network of COVID-19,and the overall effect of prevention and treatment of COVID-19 is close to that of the positive control Qingfei Paidu decoction,which is significantly better than that of the negative control Banxia Tianma Baizhu decoction.That is because compound Shuanghuanglian mainly acts on Aif1,Ccl2,Cdc20,Cxcl13,Fcer1g and other key targets.Compound Shuanghuanglian plays important role of inhibiting the inflammatory response of patients with COVID-19 and alleviating lung injury,so as to achieve the purpose of treating COVID-19.At the same time,in the initial stage of COVID-19 and other sudden infectious pneumoniausing compound Shuanghuanglian can win valuable time before finding symptomatic Chinese medicine prescription and vaccine research.

Research Status of Serum Pharmacology and Serum Pharmacochemistry of Traditional Chinese Medicine

Serum pharmacochemistry of traditional Chinese medicine has become a more accurate and rapidly developing reasonable way to analyze the effective material basis of traditional Chinese medicine in recent years. Through this method, we can select very complex Chinese medicine components and clarify the effective substances consistent with the main functions, and then separate and purify effective ingredients in traditional Chinese medicine, so as to explain the material basis of the drug effect and prove the rationality and principle of action of Chinese medicine compounds. It can show the multi-component and multi-target characteristic of traditional Chinese medicine, and after analyzing the migrating components of serum, we can explore the direct effective substances that act on the patient’s body, so as to accelerate and accurately complete the in-depth study of the effective substances of Chinese medicine.

Multi-target mechanism of triphala in cardio-cerebral vascular diseases based on network pharmacology

OBJECTIVE Numerous references made clear that triphala is revered as a multiuse therapeutic and perhaps even panacea historically.Nevertheless,the protective mechanism of triphala on cardio-cerebral vascular diseases(CCVDs)remains not comprehensive understanding.Hence,a network pharmacology-based method was suggested in this study to address this problem.METHODS This study was based on network pharmacology and bioinformatics analysis.Information on compounds in herbal medicines of triphala formula was acquired from public databases.Oral bioavailability as well as drug-likeness were screened by using absorption,distribution,metabolism,and excretion(ADME)criteria.Then,components of triphala,candidate targets of each component and known therapeutic targets of CCVDs were collected.Compound-target gene and compounds-CCVDs target networks were created through network pharmacology data sources.In addition,key targets and pathway enrichment were analyzed by STRING database and DAVID database.Moreover,we verified three of the key targets(PTGS2,MMP9 and IL-6)predicted by using Western blotting analysis.RESULTS Network analysis determined 132 compounds in three herbal medicines that were subjected to ADME screening,and 23 compounds as well as 65 genes formed the principal pathways linked to CCVDs.And 10 compounds,which actually linked to more than three genes,are determined as crucial chemicals.Core genes in this network were IL-6,TNF,VEGFA,PTGS2,CXCL8,TP53,CCL2,IL-10,MMP9 and SERPINE1.And pathways in cancer,TNF signaling path⁃way,neuroactive ligand-receptor interaction,etc.related to CCVDs were identified.In vitro experiments,the results indi⁃cated that compared with the control group(no treatment),PTGS2,MMP9 and IL-6 were up-regulated by treatment of 10μg·L^-1 TNF-α,while pretreatment with 20-80 mg·L^-1 triphala could significantly inhibit the expression of PTGS2,MMP9 and IL-6.With increasing Triphala concentration,the expression of PTGS2,MMP9 and IL-6 decreased.CON⁃CLUSION Complex components and pharmacological mechanism of triphala,and obtained some potential therapeutic targets of CCVDs,which could provide theoretical basis for the research and development of new drugs for treating CCVDs.

Neuroglobin and neuroprotection:the role of natural and synthetic compounds in neuroglobin pharmacological induction

Neuroglobin(Ngb)is a 17 kDa monomeric hexa-coordinated heme protein belonging to the globin family.Ngb is mainly expressed in neurons of the central and peripheral nervous system,although moderate levels of Ngb have been detected in non-nervous tissues.In the past decade,Ngb has been studied for its neuroprotective role in a large number of neurological disorders such as Alzheimer’s disease,Huntington’s disease,brain ischemia and hypoxia.This review discusses and summarizes the natural compounds and the small synthetic molecules capable of modulating Ngb expression that exhibits a protective role against various neurodegenerative diseases.

<i>In Silico</i>Pharmacological Analysis of a Potent Anti-Hepatoma Compound of Mushroom Origin and Emerging Role as an Adjuvant Drug Lead

Mushrooms are well-known to possess a continuum of anticancer metabolites that are vital in the development of anticancer adjuvant drug leads based on natural products. Owing to the fact that conventional cancer therapeutic methods were failed to lessen mortality caused by cancer to the estimated level with occurrence of adverse side effects, anticancer agents isolated from natural mushroom sources unarguably make an experimental research area worth mass focus today. The current study was targeted on in vitro cytotoxicity and in silico predictive pharmacological analysis of a flavonoid compound isolated from Fulvifomes fastuosus mushroom. Targeted compound was isolated from the mushroom using different chromatographic methods and identified by NMR spectrometry and mass spectrometry. Cytotoxicity experiments were carried out using MTT assay and apoptotic cells were identified by ethidium bromide/acridine orange staining. The SwissADME tool, BOILED-Egg construction model and Swiss target protein prediction software have been used to perform in silico predictive pharmacological analysis. The isolated compound has been identified as 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione by spectrometric methods. The result of MTT assay showed that 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has potent anticancer activity for hepatoma against Hep-G2 cell line (IC50 = 20.8 μg/ml) being less toxic to normal CC-1 epithelial cells (IC50 = 167.00 μM). The cells treated with compound ex-hibited apoptotic features such as cellular shrinkage, nuclear fragmentation and condensed cytoplasm. In summary, 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has shown potent anticancer properties against hepatoma with less cytotoxicity effect on normal cells. Furthermore, in silico study has revealed that properties of 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione may contribute to making a high absorption and clearance of the test compound as not interfering with the therapeutic failure of the compound. The properties of 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo-[3,2-c]pyran-3,2'-furan]-3',4-dione were compatible with well-known anticancer drug lapatinib. In conclusion, 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has a high tendency to act as a good anticancer adjuvant drug in the treatment of hepatoma.

Network pharmacology-based strategy for predicting therapy targets of Sanqi and Huangjing in diabetes mellitus

BACKGROUND A comprehensive literature search shows that Sanqi and Huangjing(SQHJ)can improve diabetes treatment in vivo and in vitro,respectively.However,the combined effects of SQHJ on diabetes mellitus(DM)are still unclear.AIM To explore the potential mechanism of Panax notoginseng(Sanqi in Chinese)and Polygonati Rhizoma(Huangjing in Chinese)for the treatment of DM using network pharmacology.METHODS The active components of SQHJ and targets were predicted and screened by network pharmacology through oral bioavailability and drug-likeness filtration using the Traditional Chinese Medicine Systems Pharmacology Analysis Platform database.The potential targets for the treatment of DM were identified according to the DisGeNET database.A comparative analysis was performed to investigate the overlapping genes between active component targets and DM treatmentrelated targets.We constructed networks of the active component-target and target pathways of SQHJ using Cytoscape software and then analyzed the gene functions.Using the STRING database to perform an interaction analysis among overlapping genes and a topological analysis,the interactions between potential targets were identified.Gene Ontology(GO)function analyses and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted in DAVID.RESULTS We screened 18 active components from 157 SQHJ components,187 potential targets for active components and 115 overlapping genes for active components and DM.The network pharmacology analysis revealed that quercetin,beta-sitosterol,baicalein,etc.were the major active components.The mechanism underlying the SQHJ intervention effects in DM may involve nine core targets(TP53,AKT1,CASP3,TNF,interleukin-6,PTGS2,MMP9,JUN,and MAPK1).The screening and enrichment analysis revealed that the treatment of DM using SQHJ primarily involved 16 GO enriched terms and 13 related pathways.CONCLUSION SQHJ treatment for DM targets TP53,AKT1,CASP3,and TNF and participates in pathways in leishmaniasis and cancer.

Network pharmacology analysis of the mechanisms of Banxia Xiexin Decoction against Ulcerative Colitis

Banxia Xiexin Decoction(BXXXD),a traditional herbal formula,has been used to treat ulcerative colitis(UC)clinically.In this study,chemical compounds and putative targets of BXXXD and UC related therapeutic targets were screened from multiple databases.The protein-protein interaction(PPI)was conducted using String database,and 31 candidate targets were screened from CytoNCA database.The Database for Annotation,Visualization and Integrated Discovery(DAVID)and Metascape database were used for Kyoto Encyclopedia of Genes and Genomes(KEGG)channel and Gene Ontology(GO)enrichment analysis respectively,and the enrichment analysis results were visualized by OmicShare platform.Meanwhile,the interaction network among Chinese herbs,active compounds,candidate targets and pathways was built by Cytoscape 3.7.2 software,and the potential compounds of BXXXD in the treatment of UC were screened.Finally,molecular docking technology was used to verify the putative key compounds.Combined with literature research,5 key compounds for the treatment of UC were identified,which are mainly involved in TNF signaling pathway,cancer signaling pathway,inflammatory bowel disease(IBD),Toll-like receptor signaling pathway,and NF-κB signaling pathway.This study provides a scientific basis for BXXXD as an effective alternative therapeutic agent for UC from a new perspective,and also provides a feasible method for basic chemical research and pharmacological research of BXXXD.