Exploration On The Medication Rules And Mechanisms Of Chinese Herbal Decoctions In Preventing And Treating Leukopenia Caused By Platinum-containing Chemotherapy For Malignant Tumor

PurposeBased on clinical research literature,data mining method was used to explore the clinical prescription medication rule of traditional Chinese medicine decoction for the prevention and treatment of platinum-containing chemotherapy leukopenia for malignant tumors,and network pharmacology was applied to explore the mechanism of action of core drug groups in the treatment of this disease,providing reference for the clinical medication for the prevention and treatment of platinum-containing chemotherapy leukopenia and further basic experiments.MethodRelevant literatures in CNKI,WanFang,VIP,China Biomedical Literature Database(CBM)and other databases will be comprehensively searched from the establishment of the database to February 2023.Literature was screened and data information was summarized to establish a database.IBM SPSS Modeler 18.0 software and IBM SPSS Statistics 25.0 software were used to discover the prescription medication rules of TCM decoction for preventing and treating leukopenia in platinum-containing chemotherapy for malignant tumors.The active ingredients and their targets of core drug groups were retrieved from the TCM Systematic Pharmacology Database and Analysis Platform(TCMSP)database,and disease targets from GeneCards and online human Mendelian genetics(OMIM)database were collected.The intersection targets of the two were selected to construct the network diagram of"TCM effective ingredients-core targets".Cytoscape 3.9.1 software was used to construct the protein interaction(PPI)network.Gene ontology(GO)and KEGG enrichment analysis were carried out on R4.2.3 software to explore the main mechanism of PPI network.Result1.Through screening,a total of 228 platinum-containing literatures were included in this study,involving 220 TCM prescriptions.Among them,there were 113 literatures specifying cisplatin in chemotherapy regimens,including 110 prescriptions.A total of 78 literatures have identified oxaliplatin in chemotherapy regimens,including 77 prescriptions.The following results are obtained:(1)The top 5 most frequently used platinum-containing chemotherapy for the prevention and treatment of malignant tumors were Radix astragalus,Poria codonopsis,atractylodes atractylodes and angelica sinensis.The high frequency associated drug pairs were mainly angelica-Astragalus,Ligustrum fructus-Astragalus,Coix seed-Astragalus,Angelica-white Rhizoma-Astragalus,etc.The four Qi of traditional Chinese medicine are mainly warm and flat.The five flavors of Chinese medicine are mainly sweet,bitter and acrid.Traditional Chinese medicine to the spleen meridian,lung meridian mainly.The top 5 drug frequency for prevention and treatment of cisplatin-containing chemotherapy leukopenia were Radix Astragalus,atractylodes atractylodes,angelica sinensis,poria codonopsis,respectively.The high frequency associated drug pairs were mainly Codonopsis Radix Astragalus,Fructus ligustrum Radix Astragalus,Radix rehmanniae Radix angelica,Tangerine peel Radix Angelica Radix Astragalus,etc.The top 5 drug frequency for prevention and treatment of oxaliplatin containing chemotherapy leukopenia were poria cocos,Astragalus,codonopsis codonopsis,atractylophala and tangerine peel.The high frequency associated drug pairs were mainly atractylodes-Astragalus and atractylodes-Poria.(2)Four clustering results were obtained by cluster analysis,which were as follows:the first group:Herba Hedyotidis,Scutellaria barbata,Coix seed,yam,Rhizoma atractyloides and licorice;The second group:Poria cocos,bran fried atractylodes,roasted licorice,codonopsis codonopsis,tangerine peel;The third group was paeony,ligusticum Chuanxiong,angelica sinensis,Rehmannia rehmannii and ginseng.The fourth group:Ligustrum Fructus,Radix pseudostellariae,wolfberry,caulis spatholobi,Astragalus.Three clustering results were obtained for the prevention and treatment of leukopenia after chemotherapy containing cisplatin,which were as follows:the first group:Paeony,Ligusticum Chuanxiong,angelica sinensis,Rehmannia rehmannii,licorice and ginseng.The second group:Pinellia pinellia,Coix seed,yam,atractylodes,Codonopsis codonopsis,poria cocos,tangerine peel.The third group:Herba Hedyotidis,Radix pseudostellariae,wolfberry,caulis spatholobi,Fructus ligustrum,Fructus ligustrum,Fructus psoraleae,Radix Astragalus,Cornus officinalis and licorice.Three clustering results were obtained for the prevention and treatment of leukopenia in chemotherapy containing oxaliplatin,respectively:the first group:cooked Rehmannia,ligusticum Chuanxiong,paeoniae paeoniae,angelica sinensis,roasted licorice,ginseng.The second group:Ligustrum Fructus,wolfberry,Radix pseudostellariae,atractylodes atractylodes,caulis spatholobi,Astragalus.The third group:Herba Hedyotidis,Scutellaria barbata,Acruginous Turmeric Rhizome,Chinese yam,Liquorice root,Fructus aurantii,Poria coix,Coix seed,Codonopsis codonopsis,Tangerine peel,Auckandia root,bran stir-fried white art,fructus amomi.(3)The core prescriptions were:Astragalus membranaceus,Poria codonopsis,angelica sinensis,atractylote,Tangerine peel,Ligustrum coix seed,Hedyotis glossus,cooked rehmannia,subspatholobi,wolfberry and licorice.Corni Fructus,Huangjing and Buguzhi can be added to prevent and treat leukopenia in cisplatin-containing chemotherapy.Auckandia root,Fructus Aurantii and Acruginous Turmeric Rhizome can be added to prevent leukopenia in chemotherapy containing oxaliplatin.2.Through network pharmacological analysis of the core drug group,the following results were obtained:In the core drug group(Astragalus membranaceus,atractylosum sinensis,angelica sinensis,codonopsis codonopsis and poria cocos),208 targets were obtained after the combination of the corresponding targets of active components,493 disease targets were collected,44 intersection targets were obtained,and 8 core targets were screened out,mainly AKT1,TNF,TP53,etc.The main signaling pathways were PI3K/Akt signaling pathway and platinum resistance signaling pathway.Conclusion1.In terms of medication rules,the core prescriptions of modern doctors for the prevention and treatment of leucopenia caused by platinum-containing chemotherapy for malignant tumors are:Astragalus,Atractylodes,Angelica,Poria,Coicis seed,dried rehmannia,Jixueteng,Wolfberry,Tangerine,Hedgitis alba,licorice.Bazhen decoction combined with ShenlingBaizhu powder is modified and modified,focusing on invigorating the spleen,supplemented by tonifying the kidney,and reusing sweet and warm medicine,but focusing on reinforcing.It is often compatible with traditional Chinese medicine such as water wetting,regulating qi and eliminating phlegm.For the prevention and treatment of leucopenia in cisplatin-containing chemotherapy,on the basis of the above core prescription,cornus officinalis,Rhizoma flavus and Fructus psoraleae can be added,focusing on the coordination of Yin and Yang,toning kidney and supplementing marrow.For the prevention and treatment of leucopenia in oxaliplatincontaining chemotherapy,on the basis of the above core prescription,Rhizoma aurantii,Fructus and zedoary can be added to regulate qi and promote blood circulation.2.In terms of mechanism of action,quercetin,luteolin and kaempferol were the main active components of platinum-containing chemotherapy in the core drug group for the treatment of leukopenia in malignant tumors.It mainly involves core targets such as AKT1,TP53 and CASP3,as well as platinum resistance signaling pathway,p53 signaling pathway and PI3K/Akt signaling pathway.