The Theoretical Study And Network Pharmacology Of Professor Yue In The Treatment Of Hashimoto Thyroiditis

ObjectiveAs the incidence of thyroid diseases increases,the demand for traditional Chinese medicine treatment of Hashimoto thyroiditis(HT)is dramatically increa sing.This study is aimed at dig deeper into the prescription of professor Yue in the treatment of hashimoto thyroiditis,as well as the target and pathway of the core drugs.MethodsNetwork pharmacology research is carried out through the innovativel core prescriptions obtained from data mining research.Via the website “GENECAR DS” and “Drugbank”,"Hashimoto thyroiditis" was used as the key word to retrieve the effective ingredients of the core drug,and the effective ingredients were converted into target genes by Pub Med database.Cytoscape 3.7.2 was used to construct the chemical-target network,analyze the parameters between the compound and the target gene,and obtain the protein-protein interaction core network(PPI).On the basis of PPI,DAVID software was used to conduct GO(Gene Ontology)analysis and Kyoto Encyclopedia of Genes and Genomes(KE GG)enrichment pathway analysis to describe Gene functions and pathways,and finally explore therapeutic targets of core drugs.Results1.Statistics of professor Yue's treatment of Hashimoto thyroiditis:(1)age distribution and gender distribution is consistent with the epidemiological statistics of HT;(2)Syndromes: the frequency distribution from high to low was liver stagnation(42%),spleen and kidney Yang deficiency(35%),phlegm and blood stasis(13%),qi and Yin deficiency(10%).(3)symptoms: put frequency in order,the result would be insomnia or poor sleep,fatigue,loose stool,irritability,constipation,palpitations,spontaneous sweating,dry mouth,throat discomfort,thyromegaly.Symptoms can be roughly summarized as local thyroid symptoms,systemic symptoms,symptoms of digestive tract,emotional symptoms;(4)Tongue image: the appearance of the most red tongue,thin white moss,reflects the disease liver qi stagnation,more with phlegm wet pathogenesis;(5)treatment methods: a total of 6,frequency from high to low summed up as the soothing of the liver and invigorating the kidney 86 times,invigorating the spleen and kidney 75 times,phlegm and stomach 67 times,15 times to calm the mind,invigorating the qi and nourishing the Yin 6 times,invigorating the blood and removing blood stasis 5 times,often with the soothing of the liver and invigora ting the spleen and invigorating the kidney as a joint treatment;6 drug use: commonly used 183 traditional Chinese medicine,frequency from high to low for Licorice(112 times),Bupleurum(86 times),Jujube(73 times),Scutellaria(70 times),Astragalus(67 times),Pinellia(60 times),Poria cocos(58 times),Atr actylodes(57 times),Gynostemma pentaphyllum(57 times),Dangshen(56 time s),etc.;With medicinal properties to taste: four in the gas with warm drugs(28 percent)the most,but the overall cold temperature trend is not obvious.Swe et(47%)was the most common,followed by bitter(27%)and spicy(24%).The most of the drugs were spleen meridian drugs(26%).2.Data mining:(1)association rule results: multiple drug exchange pairs were analyzed,among which the high-frequency two drug pairs were: bupleuralicorice combination,etc.The combination of shamisen was: bupleurum-radix scutellariae-licorice.The combination of four drugs was: scutellaria baicalens is-pinellia-bupleuricum-licorice.The combination of five herbs: bupleuru m-radix scutellariae-licorice-jujube-pinellia.And the combination of inn ovative medicine,such as astragalus membranaceus-qingfengteng-gynostem ma pentaphyllum-ganoderma lucidum-honeysuckle combination.(2)clusterin g analysis results: the internal structure of the drug,the combination of the fol lowing four basic formula: fuzheng yiqi: gynostemma pentaphyllum,ganoderma lucidum,honeysuckle vine,ivy,heather,astragalus;Shugan sanjie prescription:scutellaria,radix codonopsis,pinellia,jujube,licorice,bupleurum,ginger,forsyt hia,summerwort,zhejiang fritillary,schisandra;Tonifying the kidney and calming the gods: Chinese yam,alisma orientalis,cooked rehmannia glutinosa,radix aconiti sinensis,jujube kernel,ligusticum chuanxiong,rhizoma legatum,angeli casinensis,radix paeoniae alba,alba alba,gardenia;Resolving phlegm xingqi prescription: magnolia officinalis,Perilla leaves,tangerine peel,pachycodon,orange stem,bitter orange,cassia twig,oyster,rhizome,rhizoma coptidis,atractylodes,ginseng,cohosh,coix seed.(3)factor analysis results: five public factors were obtained,and the formula efficacy and sexual taste of the internal public factors were different,which were summarized as qi qi,Yang,Yang lift depres sion,similar to the clustering analysis results;Complex network analysis results:the core drugs are licorice,jujube,bupleurum and gynostemma pentaphyllum.3.Network pharmacology: 154 compound molecules were obtained(93 licorice,17 dates,17 bupleurum,24 gynostemma pentaphyllum).The network of compounds and targets shows that the effective compounds rank in descending order: Mol000098-quercetin-quercetin(from licorice,jujube,chaihu,gypentaphyllum),mol000422-kaempferol-kaempferol(from licorice,chaihu),mol000392-form ononetin-mononetin(from licorice),mol003896-7-methoxy-2-methyl Isoflavone-7-methoxy-2-methyl-isoflavone(from licorice)and mol000417-calycosin(from licorice)can interact with 51,17,13,12 and 11 target proteins,respectively.The selected target genes are PTGS2,AR,NOS2,PPARG,ESR1,ESR2 and DPP4,which can interact with 39,27,16,14,13,13 and 13 compounds respectively.In the above genes,PTGS2 was correlated,while esr1-esr2 and esr1-ar were closely correlated.GO analysis: high enrichment in BPGO terms are: regulati on of DNA binding transcription factor activity;high enrichment in MFGO terms are: regulation of ubiquitin-protein ligase binding and ubiquitin-like ligase binding;high enrichment in CCGO terms are: nuclear chromatin.KEGG analysis: there were 10 significant enrichment pathways,among which the main enrichment pathway was PI3K-Akt signaling pathway.Because there are few litera ture reports on the relationship between these targets and pathways and hashimoto's thyroiditis,the results of network pharmacology need to be further studied.Conclusions1.Professor Yue's treatment for Hashimoto's thyroiditis: based on liver sparseness,heavier righting,attention to emotions,and care of the spleen and sto mach.The prescription flavor is compatible by combining bitter-sweetness and yin,and spleen-sweetness and yang,and attach importance to the use of sweetness medicine.2.Professor Yue's core drugs for treating Hashimoto's thyroiditis are licorice,jujube,Bupleurum and Gynostemma.From this,a new formula "Ganzao Chai Hangfang" is proposed.3.Propose active ingredients,target genes and pathways from core drugs.Inflammatory response genes,estrogen receptor genes,and tumor-related target genes are prominent."Ganzao Chaiheng" formula acts on Hashimoto's thyroiditis in a multi-component,multi-target,multi-channel network,and the results are similar to the overall concept of traditional Chinese medicine.It is suggested that the research direction can consider the interaction of "pituitary-thyroid-gonadal axis" and the relationship between HT and thyroid tumors.