A Study On The Data Mining Of The Medication Rules For The Treatment Of DPN And The Network Pharmacological Analysis Of The Core Herbs

ObjectiveTo excavate the academic ideology and medication rules contained in the medical records about DPN patients from Department of Endocrinology of the First Affiliated Hospital of Guangzhou University.Besides,a network pharmacological analysis of the common key herbs was carried out to explore its therapeutic mechanism and provide a clue for further study.Method(1)Perform literature research from the perspective of traditional Chinese medicine and western medicine,respectively,to summarize the pathogenesis,diagnosis,dialectical type and treatment of DPN.(2)Collect 230 medical records which meet the inclusion criteria.Sort out them and standardize them.Then make frequency statistics,association rules analysis,factor analysis and cluster analysis based on the software R.Next extract the clinical experience and medication rules from the mining results.(3)Perform a network pharmacological analysis of the common key herbs.Obtain active ingredients and targets of these herbs from the database TCMSP.Obtain the targets related to DPN from six authoritative disease-target databases.Then based on the basic functions of Cytoscape and the plug-in named Biso Genet,establish the herbs-ingredients-targets network and the interaction network between the herb related targets and the disease related targets.Then make network topological analysis of the two networks,and make GO analysis and KEGG pathway enrichment analysis of the latter network using R software.At last analyze the results and discuss the potential mechanism.Results(1)General information: Among the 230 DPN patients,the age ranged from 25 to 89 years old.There was no significant difference between male and female in the number of cases.The course of disease ranged from several years to decades.The main symptoms were numbness of limbs,accompanied by dry mouth,polydipsia,fatigue,weakness,poor sleep,paresthesia,lower limb pain,tepid limbs,abdominal distension,etc.Atherosclerotic changes of extremities arteries,carotid arteries,cardiovascular and cerebral vessels were common.In terms of syndrome types,the yin syndrome accounted for about 60% and the yang syndrome accounted for about 40%.And the Shaoyin syndrome with the yang deficiency and the excess of cold and dampness accounted for the most cases,while the Shaoyang syndrome accounted for the most cases among the yang syndrome.(2)Medication rules: the herbs used were mainly belong to spleen,lung,heart,stomach,liver,kidney,bladder and gallbladder meridians.Tonic herbs,exterior resolving herbs,interior warming herbs,heat clearing herbs,diuretic and dampness infiltrating herbs were the most commonly used herbs.And they were often compatible with dampness resolving herbs,blood activating herbs,and herbs for dispelling wind and dampness,as well as herbs for resolving phlegm and relieving cough,etc.According to frequency statistics,there were thirty-five considerabaly frequently used herbs(frequency ≥ 10%).According to association rules analysis,the key herbs of each syndrome type were obtained.Specifically,the key herbs for Taiyang meridian syndrome,which was blocked by wind,cold and dampness,were Cinnamomi Ramulus,Zingiber Officinale Roscoe,Jujubae Fructus,Hedysarum Multijugum Maxim.The key herbs for Shaoyang meridian syndrome which was blocked by cold and dampness were Radix Bupleuri,Scutellariae Radix,Arum Ternatum Thunb.,Zingiberis Rhizoma,Cinnamomi Ramulus,Paeoniae Radix Alba,Zingiber Officinale Roscoe,licorice.The key herbs for the syndrome that the dampness and the heat block the Taiyin and Yangming meridians were Artemisiae Scopariae Herba,Angelicae Sinensis Radix,Atractylodes Lancea(Thunb.)Dc.,Notopterygii Rhizoma Et Radix,Saposhnikoviae Radix,Alisma Orientale(Sam.)Juz.,Scutellariae Radix,licorice.The key herbs for the Jueyin meridian syndrome blocked by the cold and dampness were Angelicae Sinensis Radix,Asari Radix Et Rhizoma,Cinnamomi Ramulus,Paeoniae Radix Alba,licorice,Aconiti Lateralis Radix Praeparata,Evodiae Fructus,Zingiber Officinale Roscoe,Jujubae Fructus.The key herbs for the Jueyin meridian syndrome with the upper heat and lower cold were Zingiberis Rhizoma,Mume Fructus,Coptidis Rhizoma,Angelicae Sinensis Radix,Asari Radix Et Rhizoma,Cinnamomi Ramulus.The three association rules,Guizhi-Baishao,Chaihu-Huangqin-Banxia,Baizhu-Fuzi-Huangqi,were considered to be the most crucial.Six common factors were screened out by factor analysis,including 29 core herbs,which were clustered into six categories by cluster analysis.Different clustering herbs were used for the treatment of different syndrome types of DPN.(3)The results of the research on the treatment for Shaoyin syndrome: The key herbs for Shaoyin syndrome with the yang deficiency and the excess of cold and dampness were Aconiti Lateralis Radix Praeparata,Poria Cocos(Schw.)Wolf.,Atractylodes Macrocephala Koidz.,Zingiberis Rhizoma,Ginsen Radix Et Rhizoma Rubra,Cinnamomi Ramulus,Paeoniae Radix Alba,Hedysarum Multijugum Maxim.,Zingiber Officinale Roscoe,licorice,etc.The core compatibility of Atractylodes Macrocephala Koidz.,Poria Cocos(Schw.)Wolf.and Aconiti Lateralis Radix Praeparata was obtained.Four common factors were screened out by factor analysis,including 22 key herbs,which were clustered into three groups by cluster analysis.Among the groups,the third group contained different classical decoctions,such as Fuzi decoction,Lizhong decoction,Huangqi Guizhi Wuwu decoction,Guizhi Renshen Decoction and Zhenwu decoction.(4)Network pharmacological analysis: The selected basic core herbs(Cinnamomi Ramulus,Paeoniae Radix Alba,Hedysarum Multijugum Maxim,Zingiber Officinale Roscoe,Zingiberis Rhizoma,Atractylodes Macrocephala Koidz.,Aconiti Lateralis Radix Praeparata,Poria Cocos(Schw.)Wolf.)contained 82 active ingredients and 228 targets.A total number of 30 directly acted targets were obtained.The core targets included HAP90AA1,AKT1,PPARG,SOD1,NOS3,PTGS2,TGFB1,IL6,etc.;The interaction sites included neuron cell body,axon cytoplasm,etc.The biological progress involved metabolism and regulation of molecules such as lipid,glucose,and proteins,as well as oxidative stress response,production of reactive oxides,migration and regulation of vascular endothelial cells,acute inflammatory responses,etc.It involved in AGE-RAGE signaling pathway,metabolic disease related pathway,inflammation signaling pathway and VEGF signaling pathway and many other signaling pathways.ConclusionThe treatment for DPN were based on the principle of tonifying yang and restore the regular move of yang,with the elimination of pathogenic factors and the unblocking of the channels.According to the principle,it focused on supplementing Qi and warming Yang,relieving exterior evil and dispersing pathogenic factors,clearing away heat and dampness,reducing infiltration,promoting the move of qi to clear away dampness,and give consideration to phlegm resolving,bowel moistening,fluid generating and blood activating.Different syndrome types were treated with different methods.The Shaoyin syndrome was treated with warming yang,dispersing cold and removing dampness.The Taiyang syndrome was treated with replenishing qi and warming meridians,promoting blood circulation and dredging collaterals.The Taiyin-Yangming syndrome was treated with clearing away heat and dampness,dispelling wind and dredging collaterals.The Jueyin syndrome with cold and dampness was treated with warming meridians,dispersing cold,removing dampness,nourishing blood,activating blood circulation and unblocking pulse.The Jueyin syndrome with the upper heat and lower cold were treated with clearing the upper heat,dispersing the lower cold and expel the internal evils.The herb pair,Guizhi-Baishao,was commonly used to harmonize Ying and Wei.The compatibility,Chaihu-Huangqin-Banxia was commonly used to harmonize Shaoyang.And the compatibility,Baizhu-Fuzi-Huangqi-Fuling was commonly used to warm yang and remove dampness.The selected common key herbs plays therapeutic effect on DPN by acting on multiple targets and multiple pathways.One of the potential mechanisms was that it mainly inhibiting the activity of AGE-RAGE pathways,and then regulating a number of downstream pathways and as a result play an anti-inflammatory,antioxidant and glucose-regulated effects.