A Network Pharmacology Study On The Treatment Of Malignant Pleural Effusion Of Lung Cancer With High Frequency Chinese Herbs Used In Clinical Chinese Herbal Compound

Objective: In order to explore and sort out the high-frequency traditional Chinese medicines used in the treatment of malignant pleural effusion of lung cancer by clinical Chinese medicine compound.Collecting the main active components and targets of the drugs is going to explore the relationship and mechanism between the targets and malignant pleural effusion of lung cancer.So that we can provide reference for clinical practitioners and related researchers.Methods: 1.Research on high-frequency Chinese medicine in clinical Chinese medicine compound: Screening Chinese medicine compound for clinical treatment of malignant pleural effusion of lung cancer,standardizing the name of Chinese medicine,applying the systems of "clinical collection","platform management","statistical report" and "data analysis" of Chinese medicine inheritance auxiliary platform(V2.5)software,analyzing the age and sex of patients and the four qi,five flavors,meridian tropism,frequency and prescription rules of Chinese medicine,and summarizing the high-frequency Chinese medicine.2.Research on network pharmacology of high-frequency Chinese medicine core drug group: Screening active components of drugs basing on TCMSP database and predicting action targets,and using Uniprot database to convert protein gene names to obtain drug targets;The disease targets of malignant pleural effusion of lung cancer were obtained by Genecards database and OMIM database.Using Venney2.1.0software to screen the intersection targets of drugs and diseases.GO function enrichment analysis and KEGG pathway enrichment analysis were carried out on intersection targets by DAVID6.8 software.The drug-component-target-pathway-disease network diagram was established by using cytoscape3.9.1 visualization software.The interaction network diagram of common target protein was constructed by using String software,and the network diagram of core target protein was constructed by using cytoscape3.9.1 software.Using KEGG software,the enrichment map of main signal paths is displayed.Results: 1.Study on clinical Chinese medicine compound prescription:A total of 303 clinical Chinese medicine compound prescriptions involving238 Chinese medicines were screened out.(1)Patients with malignant pleural effusion of lung cancer are mostly over 54 years old,with more males than females.(2)The ranking order of four gas frequencies of compound drugs is warm > cold > flat > cool > hot,mainly warm,cold and flat.The ranking order of five flavors is sweet > bitter > pungent > salty > astringent,with sweet,bitter and pungent flavors as the main ones.The ranking order of meridian tropism frequency is spleen,lung,stomach,liver,heart,kidney,bladder,large intestine,gallbladder,small intestine,pericardium and triple energizer,with spleen,lung,stomach,liver,heart and kidney meridians as the main ones,while spleen,lung and stomach meridians tend to be the top three.(3)43 medicines were used among the 303 prescriptions,which was more than 10%.And the top 10 drugs were Poria,Atractylodes macrocephala,Glycyrrhiza,Pinellia ternata,Ramulus Cinnamomi,Radix Astragali,Pericarpium Citri Tangerinae,Jujube,Codonopsis pilosula and Lepidium.(4)Setting the support degree to 60,and screening out a total of 12high-frequency combinations of Poria,Atractylodes macrocephala,Glycyrrhiza uralensis,Pinellia ternata,Ramulus Cinnamomi,Radix Astragali,Pericarpium Citri Tangerinae,Fructus Jujubae,Radix Codonopsis,Semen Lepidii,Fructus Crataegi and Fructus Hordei Germinatus.The confidence level of 0.9 verified the high correlation of nine drugs were Poria cocos,Atractylodes macrocephala,Pinellia ternata,Ramulus Cinnamomi,Radix Astragali,Pericarpium Citri Tangerinae,Fructus Jujubae,Radix Codonopsis,and Semen Lepidii.Three different confidence levels of 10%,20% and 30%were setted.10 traditional Chinese medicines including Poria,Atractylodes macrocephala,Glycyrrhiza uralensis,Pinellia ternata,Cinnamomum cassia twig,Astragalus membranaceus,Pericarpium Citri Tangerinae,Jujube,Codonopsis pilosula and Lepidium Seed,were obtained as high-frequency core medicine combinations.2.Study on network pharmacology: Six high-frequency core Chinese medicines,Poria cocos,Atractylodes macrocephala,Glycyrrhiza uralensis Fisch,Ramulus Cinnamomi,Jujube and Lepidium,contain 132 effective active ingredients,which including quercetin,kaempferol,β-sitosterol,isorhamnetin and naringin.There are 198 common drug targets.There are 2108 disease targets in malignant pleural effusion of lung cancer.Drugs and diseases have 108 intersecting targets.There were 628 biological processes,53 cell compositions,108 molecular functions were obtained by GO enrichment analysis and 166 signal pathways by KEGG enrichment among 108 intersecting targets.The core targets of six kinds of high-frequency core Chinese medicines in the treatment of malignant pleural effusion of lung cancer are STAT3,TNF,TP53,RXRA,CRP,IL6 and so on,which mainly involve tumor pathway,lipid and AGE-RAGE signaling pathway in atherosclerosis and diabetic complications.Conclusions: 1.Warm drugs are the main drugs in the treatment of malignant pleural effusion caused by lung cancer,and Linggui Shugan decoction is contained in the high-frequency core drug group,which embodies Zhang Zhongjing’s treatment principle that "those who are sick with phlegm should be treated with warm drugs".The compound treatment is mainly based on drugs that are sweet and belong to spleen meridian.And the high-frequency core drug group contains Liujunzi decoction,which embodies the therapeutic principles of "deficiency is to replenish the mother" and "strengthening the soil and generating gold".2.Six kinds of high-frequency core Chinese medicines including Poria,Atractylodes macrocephala,Glycyrrhiza uralensis Fisch,Ramulus Cinnamomi,Jujube and Lepidium Seed,which are mainly used to treat malignant pleural effusion of lung cancer through multi-components,multi-targets and multi-channels,involving the main active ingredients such as quercetin,kaempferol,β-sitosterol,isorhamnetin and naringin.STAT3,TNF,TP53,RXRA,CRP,IL6,and JAK-STAT,PI3K-Akt,PPAR,MAPK,Toll-like receptor and other signal pathways may play a role by influencing the proliferation,differentiation,apoptosis and immunomodulation of tumor cells and the generation,growth and metastasis of tumor cells.