Research On The Law And Mechanism Of Clinical Use Of Traditional Chinese Medicine In The Treatment Of Rheumatism Based On Data Mining

Objective:This study comprehensively collected Chinese medicine prescriptions for rheumatism,builds a database based on the Traditional Chinese Medicine Inheritance Assistant System(TCMISS)software platform,and uses association rules and complex system entropy clustering methods to analyze the rule of prescription.Meanwhile,network pharmacology method was used to analyze the mechanism of the drug combinations in the treatment of rheumatism,in order to elucidate the regularities and promote the reasonable application of drugs in clinical rheumatism treatment.Methods:The database was established by importing the collected rheumatism prescriptions into TCMISS software,and the association rules Apriori algorithm and complex system entropy clustering algorithm were used for data mining.Frequency statistics,group rules,and new party analysis were performed through the software analysis module to obtain high-frequency drugs,drug pairs,core combinations and new prescriptions.Different core drug combinations and network maps were obtained by setting different support levels.Combined with the theory of traditional Chinese medicine(TCM)and clinical practice results,the main drugs and new prescriptions for rheumatism treatment were analyzed"Paeoniae Radix Alba-Cinnamomi Ramulusl" and "Paeoniae Radix Alba-Aconiti Lateralis Radix Prareparata-Glyrrhizae Radix et Rhizoma" were selected for further research.The related compounds and targets were retrieved from Traditional Chinese Medicine System Pharmacology Analysis Platform(TCMSP),and the targets related with rheumatism were gathered from Therapeutic Target Database(TTD).Networks were constructed by Cytoscape3.7.0 software.To elucidate the multiple mechanisms of Paeoniae Radix Alba-Cinnamomi Ramulus and "Paeoniae Radix Alba-Aconiti Lateralis Radix Prareparata-Glycyrrhizae Radix et Rhizoma" on rheumatism from a systematic level,GO function enrichment analysis and KEGG pathway enrichment analysis were used.Results:1.Study on the rule of traditional Chinese medicine(TCM)in the treatment of rheumatism1.1 Study on the rule of total prescription medications for treating rheumatism with TCM:A total of 1294 prescriptions for rheumatism which involved 413 kinds of TCM were collected.The top five frequently adopted drugs were "Angelicae Sinensis Radix"(594),“Glycyrrhizae Radix et Rhizoma"(435),"Paeoniae Radix Alba"(361),"Astragali Radix"(336),and "Cinnamomi Ramulus"(308).The top five frequently adopted drug combinations were "Glycyrrhizae Radix et Rhizoma-Angelicae Sinensis Radix","Angelicae Sinensis Radix-Paeoniae Radix Alba","Astragali Radix-Angelicae Sinensis Radix","Chuanxiong Rhizoma-Angelicae Sinensis Radix",and "Angelicae Sinensis Radix-Cinnamomi Ramulus".Thus,the treatment of rheumatism is mainly based on tonifying qi and blood medicine,supplemented by promoting blood circulation and removing blood stasis,clearing away heat and so on,and focusing on the compatibility of drugs.24 core drug combinations and 12 new prescriptions were gathered based on entropy clustering analysis.Among them,4 prescriptions might have some guiding value for clinical practice."Atractylodis macrocephalae Rhizoma Poria Ginseng Radix et Rhizoma_Alismatis Rhizoma_Phellodendri Chinensis Cortex_Atractylodis Rhizoma" combination has the effect of clearing away heat and eliminating dampness,inducing diuresis to alleviate edema;"Scolopendra_Eupolyphaga Steleophaga_Zaocys_Vespae Nidus" combination has the effect of calming endogenous wind and relieving spasm,promoting blood circulation for removing blood stasis;"Epimedii Folium_Psoraleae Fructus_Drynariae Rhizoma_Dipsaci Radix Cibotii Rhizoma" combination has the effect of promoting blood circulation for removing blood stasis,nourishing kidney-yang;"Chuanxiong Rhizoma_Saposhnikoviae Radix_Paeoniae Radix Alba_Carthami Flos_Genkwa Flos_Persicae Semen" combination has the effect of dispelling wind and relieving pain,promoting blood circulation for removing blood stasis.1.2 Study on the rule of high frequency drug prescriptions:The prescriptions of the top five high frequency drugs were analyzed.The gathered drug combinations were that the combination of tonifying qi and blood medicine,supplemented by blood-activating and stasis-dissolving drugs and relieving exterior syndrome drugs.Two drugs were found used frequently in combination through the core combination analysis,namely,"Carthami Flos-Persicae Semen" for activating blood circulation to dissipate blood stasis and"Eucommiae Cortex-Dipsaci Radix" for yang-tonifying.2 Study on the prescription medication rules for rheumatoid arthritis treated by TCM2.1 Study on the rule of overall prescription medication:A total of 113 prescription which involved 197 kinds of TCM were collected.The top five frequently adopted drugs were "Angelicae Sinensis Radix"(51),"Cinnamomi Ramulus"(47),"Paeoniae Radix Alba"(40),"Astragali Radix"(36),"Glycyrrhizae Radix et Rhizoma"(30),and they were same as the top five total prescription medications for rheumatism.The treatment of rheumatism is mainly based on tonifying qi and blood medicine,The most frequent drug combination was"Paeoniae Radix Alba-Cinnamomi Ramulus".New prescription by entropy clustering was gathered,namely,"Vespae Nidus_Zaocys_Eupolyphaga Steleophaga Dipsaci Radix Taxilli Herba Trachelospermi Caulis et Folium".It is mainly based on rheumatism-dispelling drugs,supplemented by yang-tonifying drugs and blood-activating and stasis-dissolving drugs,which dispelling cold and removing dampness,warming and activating meridian.2.2 Study on the rule of high frequency prescription medication:The prescriptions of the first three high-frequency drugs were analyzed,and the common drug pairs were obtained as a combination of drugs for nourishing qi and blood and relieving exterior syndrome.And they were same as the rule of high frequency prescription medication for rheumatism.The core drug combinations were based on the core combination of the total prescriptions,supplemented by Rehmanniae Radix Praeparata for antianemic,Atractylodis macrocephalae Rhizoma for tonifying qi,Cinnamomi Ramulus and Saposhnikoviae Radix for relieving exterior syndrome,Aconiti Lateralis Radix Prareparata for dispelling internal cold.The TCM prescription "Paeoniae Radix Alba-Aconiti Lateralis Radix Prareparata-Glycyrrhizae Radix et Rhizoma" was extracted from the core drug combination,which is derived from“Shanghan Lun" and used to treat anemofrigid-damp arthralgia.It was worthy for further discussion3 Study on the rule of prescription medication of TCM for gout3.1 Study on the rule of overall prescription medication:A total of 77 prescription which involved 178 kinds of TCM were collected.The top five frequently adopted drugs were "Phellodendri Chinense Cortex"(44),"Coicis Semen"(43),"Atractylodis Rhizoma"(34),"Smilacis Glabra Rhizoma"(33),"Glycyrrhizae Radix et Rhizoma"(30),and they were totally different from the top five total prescription medications for rheumatism.The treatment of gout was mainly composed of heat-clearing drugs,blood-activating and stasis-dissolving drugs,diuresis and eliminating dampness drugs.The most frequent drug combination was "Phellodendri Chinense Cortex-Atractylodis Rhizoma".New prescription by entropy clustering was gathered,namely,"Chuanxiong Rhizoma Lonicerae Japonicae Flos Carthami Flos_Paeoniae Radix Rubra Cyathulae Radix Pheretima".It is mainly composed of blood-activating and stasis-dissolving drugs and heat-clearing drugs,which could swell and disperse blood stasis,dispel wind and heat.3.2 Study on the rule of high frequency prescription medication:The prescriptions of the first three high-frequency drugs were analyzed,and the common drug pairs were obtained as a combination of heat-clearing drugs and diuresis and dampness-eliminating drugs.And they were different from the rule of high frequency prescription medication for rheumatism.The core drug combination "Atractylodis Rhizoma-Phellodendri Chinensis Cortex-Coicis Semen" was obtained through the setting of different support levels,which is an important part of Simiao Pill4 Study on compatibility mechanisms of drug pairs based on network pharmacology.4.1 Study on the mechanism of "Paeoniae Radix Alba-Cinnamomi Ramulus" in the treatment of rheumatoid arthritisAll chemical components of Paeoniae Radix Alba and Cinnamomi Ramulus were searched from TCMSP,including 85 compounds in Paeoniae Radix Alba,220 compounds in Cinnamomi Ramulus.Based on oral bioavailability(OB)?30%and drug-like(DL)?0.18 as screening conditions,17 candidate compounds and 94 potential targets were obtained.A total of 88 rheumatoid arthritis related targets were gathered from disease database.We constructed drug-target-disease network and enrichment analysis,and predicted the pharmacological mechanism of "Paeoniae Radix Alba-Cinnamomi Ramulus"in treating rheumatoid arthritis might relate with several targets,namely,IL6,TNF,JUN,PTGS2 etc.and rheumatoid arthritis and osteoclast differentiation signaling pathway.4.2 Study on the mechanism of "Paeoniae Radix Alba-Aconiti Lateralis Radix Prareparata-Glycyrrhizae Radix et Rhizoma" in the treatment of rheumatoid arthritisAll chemical components of Paeoniae Radix Alba,Aconiti Lateralis Radix Prareparata and Glycyrrhizae Radix et Rhizoma were searched from TCMSP,including 85 compounds in Paeoniae Radix Alba,65 compounds in Aconiti Lateralis Radix Prareparata and 280 compounds inGlycyrrhizae Radix et Rhizoma.Based on oral bioavailability(OB)?30%and drug-like(DL)?0.18 as screening conditions,48candidate compounds and 94 potential targets were obtained.A total of 88 rheumatoid arthritis related targets were gathered from disease database.We constructed drug-target-disease network and enrichment analysis,and predicted the pharmacological mechanism of "Paeoniae Radix Alba-Aconiti Lateralis Radix Prareparata-Glycyrrhizae Radix et Rhizoma" in rheumatoid arthritis treatment might relate with several targets,namely,IL6,TNF,JUN etc.and rheumatoid arthritis and osteoclast differentiation signaling pathway.Conclusion:1 The treatment of rheumatism in TCM was based on the principle of supporting healthy energy and eliminating pathogenic factors,supplemented by the methods of promoting blood circulation and removing blood stasis,clearing away heat and detoxifying toxins.Meanwhile,paying attention to relieve qi stagnancy in liver and regulate the spleen and stomach Tonic drugs,rheumatism-dispelling drugs,heat-clearing drugs,blood-activating and stasis-dissolving drugs,and exterior syndrome-relieving drugs were more used.The high-frequency drugs were Angelicae Sinensis Radix,Glycyrrhizae Radix et Rhizoma,Paeoniae Radix Alba,Astragali Radix,and Cinnamomi Ramulus.Drug combinations used classical prescriptions or adjust additions and subtractions based on them.2 The main treatment principle of TCM for rheumatoid arthritis was to relieve pain and improve disease syndromes.Drugs such as tonifying qi and blood,dispelling wind and removing obstruction in the meridians,dispelling cold and removing dampness are more used.The high-frequency drugs were Angelicae Sinensis Radix,Cinnamomi Ramulus and Paeoniae Radix Alba.3 The main treatment principle of TCM for gout was to clear heat andeliminate dampness.Mostly used as heat-clearing drugs in combination with diuresis and dampness-eliminating drugs and rheumatism-dispelling drugs.Meanwhile,the combined application of several methods of removing dampness,infiltrating dampness and drying dampness.The high-frequency drugs were Phellodendri Chinense Cortex,Coicis Semen and Atractylodis Rhizoma4 Through the network analysis of multi-component and multi-target of "Paeoniae Radix Alba-Cinnamomi Ramulus" and "Paeoniae Radix Alba-Aconiti Lateralis Radix Prareparata-Glycyrrhizae Radix et Rhizoma",it was preliminarily speculated that the mechanism of rheumatoid arthritis treatment might through IL6 and TNF regulated osteoclast differentiation signaling pathway to exert a therapeutic role.Furthermore,the analysis revealed a pathway for rheumatoid arthritis,which might be more closely related to the nature of the disease and deserved further exploration.