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.

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.

Chemical composition and pharmacological activities of Atractylodes lancea:A review

Atractylodes lancea(called Cangzhu in China)is a medicinal plant that has long been used as tonic agent in various ethno-medical systems in East Asia,especially in China,for the treatment of gastrointestinal dysfunction,cancer,osteoporosis,obesity and fetal irritability.We used the TCMSP database to search for the main active ingredients and traditional Chinese medicine targets of Atractylodes macrocephala.There are a total of 38 related articles,of which 27 are closely related to chemical composition and activity.This study reviews the chemical components and pharmacological effects of A.lancea,aiming to provide reference for its further research and development.

Effects of Different Initial Processing Methods on Atractylodin Content of Atractylodes chinensis

[Objectives]The paper was to compare the effects of different initial processing methods on atractylodin content of Atractylodes chinensis.[Methods]The atractylodin content of A.chinensis obtained by different initial processing methods was determined by HPLC.The loss rate on drying was determined by weighing.[Results]In the study of drying methods,the atractylodin content varied significantly among different thicknesses of slices,and the overall content of the product with the slice thickness of 5 mm was higher.Among different drying methods,constant temperature vacuum drying and shade drying of 5 mm slice resulted in the highest content of atractylodin.In the experiment of root impacting,root impacting twice received the best effect,and there was no significant difference in the atractylosin content of A.chinensis between drying in the sun and drying in the shade after root impacting twice(P>0.05).[Conclusions]Constant temperature vacuum drying or drying in the shade with the slice thickness of 5 mm,and root impacting twice is the best initial processing method,which leads to high atractylodin content of A.chinensis and good quality of medicinal materials.

Actinidia chinensis Planch.root extract downregulates the Wnt/β-catenin pathway to treat gastric cancer:a mechanism study based on network pharmacology

Background:Actinidia chinensis Planch.roots(AcRoots)have been applied as an anti-inflammatory and antitumor drug in the treatment of gastric cancer(GC).However,their mechanisms against GC cells remain unclear.To investigate the anticancer effect of AcRoots in GC and the possible underlying mechanism by using network pharmacology.Methods:Differentially expressed genes between gastric precancerous lesions and cancer were analyzed in Gene Expression Omnibus datasets,and these genes were overlapped with potential targets of AcRoots.Potential targets and pathways for AcRoots treatment of GC predicted by network pharmacology.Furthermore,we used the GC cell line HGC27 to explore the molecular mechanisms in the context of hub genes in apoptosis,invasion,metastasis,and epithelial to mesenchymal transition-promoting factors.Molecular docking between hub targets and active drug components was also performed.Results:Network pharmacological analysis suggested that the potential mechanism was related to the Wnt pathway and predicted nine hub genes.In in vitro studies,AcRoots significantly decreased HGC27 cell viability and promoted apoptosis by upregulating caspase3 and downregulating Bcl2.Moreover,it suppressed invasion and metastasis as well as the expression of epithelial to mesenchymal transition-related factors.In addition,AcRoots affected the phosphorylation level of GSK3β(Ser9)in the Wnt pathway to promote the degradation ofβ-catenin,resulting in the downregulation of the downstream target genes c-myc,cyclin D1 and snail.All the experimental results were consistent with the network pharmacology results.Conclusion:This study combined network pharmacology with in vitro experiments to provide valid evidence for the clinical promotion of AcRoots.

Lignans are the main active components of Schisandrae Chinensis Fructus for liver disease treatment:a review

As a traditional Chinese herbal medicine,Schisandrae Chinensis Fructus(SC)has been used in medicine and food industry due to its health care and therapeutic effects.Over the past 20 years,the use of SC and its active ingredient lignans in the prevention and treatment of liver diseases has been increasing,and their hepatoprotective effects has increased the interest of the public and academia.Therefore,in the present work,we first determined the effectiveness of SC in the treatment of liver diseases such as metabolic associated fatty liver disease,alcoholic liver disease,cholestatic liver disease and acute liver injury.Subsequently,the pharmacological effects and molecular mechanisms of lignans,the active components of SC,for liver disease treatment were comprehensively summarized for the first time.The results showed that the lignans in SC could achieve hepatoprotective effects by regulating lipid metabolism,anti-fibrosis,anti-inflammation,anti-oxidation,anti-tumor and regulating bile acid metabolism.The mechanism mainly involved adenosine 5’-monophosphate-activated protein kinase,endoplasmic reticulum stress,sterol regulatory element binding protein 1c,autophagy,transforming growth factor-β,mitogen-activated protein kinase,microRNA,nuclear factor kappa-B,nuclear factor erythroid-2-related factor 2,heat shock proteins and pregnane X receptor signaling pathways.These results can lay a scientific foundation for the development of hepatoprotective drugs or functional foods from SC/lignans.

Network pharmacology and molecular dynamics study of the effect of the Astragalus-Coptis drug pair on diabetic kidney disease

BACKGROUND Diabetic kidney disease(DKD)is the primary cause of end-stage renal disease.The Astragalus-Coptis drug pair is frequently employed in the management of DKD.However,the precise molecular mechanism underlying its therapeutic effect remains elusive.AIM To investigate the synergistic effects of multiple active ingredients in the Astragalus-Coptis drug pair on DKD through multiple targets and pathways.METHODS The ingredients of the Astragalus-Coptis drug pair were collected and screened using the TCMSP database and the SwissADME platform.The targets were predicted using the SwissTargetPrediction database,while the DKD differential gene expression analysis was obtained from the Gene Expression Omnibus database.DKD targets were acquired from the GeneCards,Online Mendelian Inheritance in Man database,and DisGeNET databases,with common targets identified through the Venny platform.The protein-protein interaction network and the“disease-active ingredient-target”network of the common targets were constructed utilizing the STRING database and Cytoscape software,followed by the analysis of the interaction relationships and further screening of key targets and core active ingredients.Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichments were performed using the DAVID database.The tissue and organ distributions of key targets were evaluated.PyMOL and AutoDock software validate the molecular docking between the core ingredients and key targets.Finally,molecular dynamics(MD)simulations were conducted to simulate the optimal complex formed by interactions between core ingredients and key target proteins.RESULTS A total of 27 active ingredients and 512 potential targets of the Astragalus-Coptis drug pair were identified.There were 273 common targets between DKD and the Astragalus-Coptis drug pair.Through protein-protein interaction network topology analysis,we identified 9 core active ingredients and 10 key targets.GO and KEGG pathway enrichment analyses revealed that Astragalus-Coptis drug pair treatment for DKD involves various biological processes,including protein phosphorylation,negative regulation of apoptosis,inflammatory response,and endoplasmic reticulum unfolded protein response.These pathways are mainly associated with the advanced glycation end products(AGE)-receptor for AGE products signaling pathway in diabetic complications,as well as the Lipid and atherosclerosis.Molecular docking and MD simulations demonstrated high affinity and stability between the core active ingredients and key targets.Notably,the quercetin-AKT serine/threonine kinase 1(AKT1)and quercetin-tumor necrosis factor(TNF)protein complexes exhibited exceptional stability.CONCLUSION This study demonstrated that DKD treatment with the Astragalus-Coptis drug pair involves multiple ingredients,targets,and signaling pathways.We propose a novel approach for investigating the molecular mechanism underlying the therapeutic effects of the Astragalus-Coptis drug pair on DKD.Furthermore,we suggest that quercetin is the most potent active ingredient and specifically targets AKT1 and TNF,providing a theoretical foundation for further exploration of pharmacologically active ingredients and elucidating their molecular mechanisms in DKD treatment.

Pulsatilla chinensis:phytochemistry,pharmacology and new drug development

Pulsatilla chinensis is a widely used traditional Chinese herb,which contains 56 types of chemical constituents,mainly including triterpenoid saponins,organic acids,coumarins and lignans.The largest portion of the ingredients in Pulsatilla chinensis is the family of triterpenoid saponins,in which anemoside B4 is the major effective compound and indexing component.The main components of Pulsatilla chinensis can metabolize into a vast array of active products in vivo,which play vital roles in its biological activity.Mounting evidence reveals that Pulsatilla chinensis exerts a wide range of therapeutic activities,such as anti-cancer,immunoregulation,anti-inflammation and anti-schistosome,with fewer adverse reactions,via various signaling pathways and multiple targets.It was documented that the active ingredient of Pulsatilla chinensis can lessen the drug resistance and synergize the effects of other natural products including paclitaxel,as well as ameliorate the clinical efficacy of chemical drugs,such as adriamycin.However,Pulsatilla chinensis was also reported to be possibly the main cause of hemolysis and chronic liver injury.The efforts should be made to deeply investigate the pharmacological actions and underlying mechanisms of Pulsatilla chinensis,with a focus on the anti-cancer efficacy,and develop new drugs based on the components of Pulsatilla chinensis for future utilization in the clinical setting.

Study on the Mechanism of Atractylodes lancea in the Treatment of Diabetes Based on Network Pharmacology

[Objectives]To predict the mechanism of Atractylodes lancea in the treatment of diabetes by using the method of network pharmacology.[Methods]The active constituents of A.lancea were mined and their action targets were predicted by using TCMSP database,and the targets of diabetes were screened out by GeneCards,and OMIM databases.The"constituent-target-pathway-disease"network of A.lancea in the treatment of diabetes was constructed by using Cytoscape software.The target protein-related interaction network was constructed by STRING database,and the biological function annotation and pathway analysis of key targets were carried out.[Results]The 4 active constituents of A.lancea could treat diabetes by intervening in 47 targets,95 GO biological processes and 116 main biological pathways.[Conclusions]The wogonin,NSC63551,3β-acetoxy atractylone andβ-carotene in A.lancea may regulate nuclear receptor activity,transcription factor activity(directly bind to the ligand-regulated sequence-specific DNA),steroid receptor,G protein-coupled amine receptor activity,sodium-chloride transporter activity,neurotransmitter receptor activity and other pharmacological effects,by mediating AGE-RAGE pathway,IL-17 pathway,PI3K-Akt pathway,p53 pathway,etc.,so as to treat diabetes.

Quality Evaluation of Atractylodes chinensis(DC.)Koidz.in Chengde Region Based on Dual Component Analysis

[Objectives]To evaluate the quality of Atractylodes chinensis(DC.)Koidz.in Chengde region.[Methods]35 samples of A.chinensis from different growth years were collected,and a high performance liquid chromatography(HPLC)method was established for the dual components of atractylodin and atractylone,and the quality evaluation was conducted on the cultivated A.chinensis from Chengde region in terms of moisture,ash and volatile oil content.[Results]The moisture content of all samples met the regulations,and the content of volatile oil was relatively high.Among them,seven samples with atractylodin content lower than 0.3%were unqualified products(accounting for 20%),and one sample had excessive ash content(accounting for 3%).[Conclusions]The established method for the determination of the dual components of Atractylodis Rhizoma is stable,simple,fast,precise and reusable.Besides,according to the Pearson correlation analysis among the indicators,it is concluded that the atractylodin and atractylone content are significantly related to the growth period and the volatile oil content.In addition,the quality evaluation indicators of A.chinensis in Chengde region show that there are differences in the quality of Atractylodis Rhizoma,but the overall pass rate is relatively high.It is necessary to further study the reasons for the differences.

Pharmacodynamic Substance and Mechanism of Atractylodes macrocephala in Treating PD Based on LC-MS and Network Pharmacology Technology

[Objectives]The paper was to explore the pharmacodynamic substances and mechanism of Atractylodes macrocephala in treating primary dysmenorrhea(PD).[Methods]The components of A.macrocephala were qualitatively identified by ultra high performance liquid chromatography quadrupole-time of flight mass spectrometry(UPLC-MS)combined with analyst TF 1.7.1 and peakview 2.2 software with reference to internal databases and literatures.The chemical components of A.macrocephala and the target of PD were collected by using network pharmacological data.The common genes were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)of genes and genomes with the help of String database and Metascape platform,and the affinity between core molecules and key targets was verified.[Results]A total of 23 chemical components of A.macrocephala were identified,and 301 gene targets of chemical components of A.macrocephala,614 targets of PD,and 25 intersection targets were obtained.GO analysis results obtained 505 biological processes,11 cellular components,and 33 molecular functions.KEGG pathway analysis showed that it mainly involved TNF signaling pathway,IL-17 signaling pathway,estrogen receptor signaling pathway and arachidonic acid metabolism.The top 4 targets of PPI network centrality and the top 5 compounds of A.macrocephala-component-target-disease network centrality were selected for docking.The docking results showed that atractylenolide I,Selinar-4(15),7(11)-dien-8-one,and atractylenolide II had strong binding ability.[Conclusions]A.macrocephala may exert a curative effect on PD by targeting atractylenolide I,Selinar-4(15),7(11)-dien-8-one,and atractylenolide II on key targets such as TNF,IL6,IL1β,PTGS2 to regulate cellular TNF signaling pathway,IL-17 signaling pathway,estrogen receptor signaling pathway,and arachidonic acid metabolism.

Study on the Mechanism of Angelica sinensis-Phellodendri Chinensis Cortex in the Treatment of Chronic Prostatitis Based on Network Pharmacology

[Objectives]To explore the mechanism of Angelica sinensis-Phellodendri Chinensis Cortex in the treatment of chronic prostatitis(CP)based on the method of network pharmacology.[Methods]The active components and action targets of Angelica sinensis-Phellodendri Chinensis Cortex were screened by(TCMSP),a systematic pharmacological analysis platform of traditional Chinese medicine,combined with literature search.The target was corrected by Uniprot database,and the disease CP target was screened by GeneCards and OMIM database.The common targets of drugs and diseases were screened by R language software,and the visual network map of drugs-active components-targets-diseases was constructed by Cytoscape 3.5.1 software.The common target protein-protein interaction(PPI)network was constructed by using STRING platform.The R language software was used to annotate and analyze the gene function and pathway of the core target through geneontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).[Results]46 active components of Angelica sinensis-Phellodendri Chinensis Cortex were screened,and 212 related targets were predicted,of which 159 were related to disease.These targets were mainly involved in biological processes such as heterologous biological stimulation,oxidation and anti-oxidation,and were mainly concentrated in PI3K-Akt,mitogen-activated protein kinase(MAPK),hypoxia inducible factor-1(HIF-1)and other related signaling pathways.[Conclusions]The multi-component,multi-target and multi-pathway action characteristics of Angelica sinensis-Phellodendri Chinensis Cortex were confirmed by network pharmacology,and the possible mechanism of Angelica sinensis-Phellodendri Chinensis Cortex in the treatment of CP was predicted,which provided a theoretical basis for further experiments to verify its action mechanism.

A network pharmacology-based study on the anti-hepatoma effect of Phellodendri Chinensis Cortex

Traditional Chinese medicine(TCM)Phellodendri Chinensis Cortex(PCC)has been used for the treatment of human hepatocellular carcinoma,but the underlying mechanisms are still unclear.In this study,15 active compositions of PCC were obtained from Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),and 505 putative identified targets of PCC were screened by Swiss Target Prediction server.Next,HCC data was downloaded from Drugbank and GeneCards databases.Furtherly,45 common targets were revealed.The network diagrams of the active component-target network,protein-protein interaction(PPI)network and active component-target-pathway network were constructed using Cytoscape software.The analysis of the network results showed that the active ingredients of PCC,such as berberine,obacunone,rutaecarpine,candletoxin A,palmatine,isocorypalmine,quercetin,and(S)-Canadine,had a good binding activity with more targets.Additionally,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses revealed that common targets were significantly enriched in Ras signaling pathway,ErbB signaling pathway,and Mammalian target of rapamycin(mTOR)signaling pathway.Altogether,the multi-component,multi-target,and multi-pathway characteristics of PCC provided a reference for the in-depth study of the mechanism of PCC in the treatment of HCC.

Therapeutic potential and pharmacological activities of Atractylodes lancea (Thunb.) DC.

The rhizome of Atractylodes Iancen(A.lancea)(Thunb.) DC.(AL)is extensively used in Chinese,Thai,and Japanese traditional medicines as crude extracts/decoctions or a component in various herbal formulations.Various pharmacological activities of Al.and its major constituents have been demonstrated in ritro.ex ciro.and in animal models.Results from the toxicity studies in animal models suggest safety profile of AL,and its active constituents.Despite extensive use with positive impression in many diseases,there has not been a clinical study that can conclusively support its efficacy and safely profile in human.This review comprehensively summarizes current information on the pharmacological activities of AL and their active constituents including anticancer,anti-inflammatory,antimicrobial and antipyretic activities,as well as activities on central nervous,cardiovascular,and gastrointestinal systems.

Effects of plug tray cell size on the growth of Atractylodes Chinensis (DC) Koidz seedlings

Atractylodes Chinensis(DC)Koidz is a perennial herb often used as a prescription medicine for influenza,to invigorate the spleen and remove dampness.The quality of the herb is determined by the quality of the seedlings.The traditional A.chinensis seedling production technique has nonuniform seedlings and low mechanisation.The plug seedling technique was used to produce A.Chinensis seedlings.This study was conducted to determine the growth characteristics of A.Chinensis seedlings according to the cell size of plug trays and number of days after sowing.Plant height,stem diameter,rhizome diameter,number of leaves,leaf area,and shoot dry and fresh weight of A.Chinensis seedlings were significantly higher in the P32-D treatment than in the P72,P50,and P32 treatments,but not significantly different from the P28-D treatment 60 d after sowing.The P28-D treatment resulted in a considerable drop in rhizome fresh weight and healthy seedling index,both of which are key indicators for assessing seedling quality.Although the differences in Pn among treatments were not significantly different,Tr was considerably greater in A.Chinensis seedlings treated with P32-D and P28-D than in the other three treatments.The P32-D and P28-D treatments had considerably greater potential maximum photochemical efficiency of PSII,quantum yield of photosystem II,photochemical quenching and electron transport rate than the other three treatments.Root vitality of A.Chinensis seedlings was significantly stronger in the P32-D treatment than in the other four treatments,and it was 1.9 times higher than in the P28-D treatment.The soluble protein,soluble sugar,and starch contents of A.Chinensis seedlings were highest in the P32-D treatment,but the differences among treatments were not significant.LUE,EUE,PY and EY were significantly higher in the P32-D treatment than in the other four treatments,being 1.3,1.3,1.4 and 1.4 times higher than in P28-D,respectively.On the other hand,as for the change in the growth of A.Chinensis seedlings according to the number of days after sowing,the growth of shoots and rhizome was most vigorous at the 60 d after sowing,while the fresh weight of the rhizome,which can be considered as an indicator of root growth,increased steadily during the experiment but slowed down after 60 d.As a result,32-cell deepened plug trays and a seedling nursery for a period of 60-75 d are recommended for commercial cultivation of A.Chinensis seedlings.This will provide technical support for production in A.Chinensis seedling.

Advances in research on chemical constituents,pharmacological actions and processing of atractylodes macrocephala

Rhizome atractylodes macrocephalae is the dry roots of Atractylodes macrocephala Koidz.It is one of commonly used Chinese medicine.In the "Shennong′s Herbal",it was listed as the top grade.It mainly contains volatile oil,atractylenolides,atractylodes polysaccharides,glycosides and amino acids.And it has the medical functions of good for spleen and intestine,diuretic and dehumidification,hidroschesis,miscarriage prevention and soon.In order to provide references for further development and utilization,this paper systematic arranged the Chinese medicine atractylodes chemical composition,pharmacological effects,processing technology and effect of processing technology on chemical composition and pharmacological action.

Study of Total Alkaloids from Rhizoma Coptis Chinensis on Experimental Gastric Ulcers

Objective： To study the effects of total alkaloids （TA） extracted from Rhizoma Coptis Chinensis on experimental gastric ulcer models. Methods： Four kinds of experimental ulcer models were established respectively by water-immersion stress, intragastric ethanol, acetic acid erosion, and pylorus ligation. The anti-ulcer effects of TA were evaluated, and compared with that of berberine （Bet） and cimetidine （Oim）. Results： TA showed significant inhibitory effects on ulcerative formation induced by water-immersion stress, intragastric ethanol, and pylorus l igation in dose-dependent manner, and showed therapeutic effect on acetic acid erosion-inducing ulcer, in comparison with the control group. The anti-ulcer activity of Bet was less than TA containing equal content of Bet. TA significantly reduced the free acidity, total acidity and total acid output, but didn＇t affect the gastric juice volume, gastric pepsin activity, adherent mucus quantity of stomach wall and free mucus dissolving in gastric juice. The suppressive activities of TA on gastric acid secretion didn＇t occur when it was administered into dodecadactylon at a dose of 360 mg/kg wt. Moreover, when compared with Oim, the inhibitory effect of TA on gastric acid secretion isn＇t proportional to the inhibitory effects on the formation of the 4 kinds of experimental ulcers. Conclusion： TA is a potent candidate in therapeutic drugs for treating gastric ulcer. Its anti-ulcer effective components and mechanism is not only related to Bet and inhibition of gastric acid, but also to other ingredients of TA and mechanism so far unknown.

Research Progress of Pholidota chinensis Lindl.

Pholidota chinensis Lindl. is a plant in Pholidota of Orchidaceae family~[1],as well as a traditional edible and medicinal plant in Guangxi Province,and has the effects of clearing away heat and nourishing yin,and preventing phlegm form forming and stopping coughing. In this paper,the research on the herbal medicine,medicinal identification,chemical composition and extraction process of some chemical components,trace elements,clinical application and pharmacological action,antibacterial effect were reviewed. The existing problems in the current research were analyzed,and its future research direction were prospected,with an attempt to provide reference for its future research and development and utilization.

Study on the mechanism of“Salvia chinensis and Radix Ranunculi Ternati”drug pair in the treatment of lung cancer

Objective:To explore the molecular biological mechanism of the"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer based on network pharmacology.Methods:Searching the TCMSP database and previous literatures to screen the active compounds which resist lung cancer activity in salvia chinensis and radix ranunculi ternati.The candidate compounds were unified in the DrugBank to find the corresponding drug targets which were corrected to the standard gene names by the UniProt database.The Swiss Target Prediction platform was used to predict other targets.Searching GeneCards,OMIM and DrugBank to obtain genes related to lung cancer.After taking the intersection,the candidate gene target of drug pair in the treatment of lung cancer could be obtained.The"herbs-compounds-targets-disease"network was bulit with Cytoscape,and the PPI network was bulit on the STRING platform while the core network nodes were screened.GO and KEGG analysis on candidate genes was implemented through Metacape platform,and a"pathways-targets"network was bulit to further screen key genes.Results:A total of 16 active compounds in salvia chinensis,18 active compounds in radix ranunculi ternati,164 candidate targets,2443 GO functions and 170 KEGG pathways was obtained.Conclusion:The effective compounds of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer are quercetin,ursolic acid,β-sitosterol and caffeic acid.The key targets are MAPK1,AKT1,PIK3R1,RAF1 and EGFR.GO functions mainly include cytokines,oxidative stress,plasma membrane transmission,protein kinase binding and activity,apoptosis.KEGG could directly regulate pathways in cancer,non-small cells lung cancer pathway and small cell lung cancer pathway.KEGG also involves EGFR tyrosine kinase inhibitor resistance,IL-17,TNF,PI3K-AKT signaling pathway and apoptosis.This study reveals the molecular biological mechanism of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer.It is reasoned that its potential targets affect multiple signaling pathways and ultimately resist the proliferation,differentiation,invasion,metastasis and promote apoptosis of lung cancer cells.Evidence for further experimental study is provided by this study.

Protective effects of Pulsatilla chinensis Regel against isoproterenol-induced heart failure in mice

Objective:To study the cardioprotective effect of Baitouwen(Pulsatilla chinensis Regel,PR)in isoproterenol(ISO)induced heart failure in mice,and investigated the molecular targets using network pharmacological prediction and experimental validation.Methods:PR were orally administered to ISO induced HF mice for two weeks.The cardiac function was analyzed by echocardiography.Hematoxylin-eosinstaining(HE)was used to evaluate the pathological changes.The PR targets for HF were predicted by bioinformatics analysis tool(BATMAN-TCM).The expression of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),and HF related genes Phosphodiesterase(PDEs),were detected by real-time fluorescence quantitative PCR or Immunohistochemical staining in heart tissues.Results:Cardiac hypertrophy was observed after ISO treatment,and hypertrophic cardiomyocytes were arranged in disorder.Moreover,the expression of ANP and BNP gene in myocardium were upregulated(P<0.05).Treatment of HF mice with PR aqueous extract improved cardiac function characterized by enhanced ejection fraction(EF)and fraction shortening(FS).Furthermore,PR extract also downregulated the expression of ANP and BNP in the heart tissues.Arrangement of cardiomyocytes was also improved.Furthermore,administration of PR group decreased target genes PDE5 and PDE1C expression in the hearts.In addition,PR treatment also improved myocardial fiber distribution and decreased myocardial thickness in the hearts of HF mice.Conclusion:PR treatment may suppress cardiac hypertrophy and improve myocardial function in HF mice via inhibiting the predicted targets PDE5 expression.These results suggest the potential of using PR in preventing the development of HF.