Prof. Li Yueqing's Prescription Analysis And Network Pharmacology Study For Kidney Deficiency Type Oligoasthenozoospermia

Objective:Nowadays,male oligoasthenospermia has become an important cause of reduced male sperm level.Modern research is still unclear on the etiology and pathogenic factors of male oligoasthenospermia,and clinical treatment is still based on empirical medication.The efficacy of traditional Chinese medicine in the treatment of male oligoasthenozoospermia has gradually been recognized by andrology.Professor Li Yueqing has unique clinical experience in the treatment of this disease.In this study,the software "TCM inheritance assistance system(TCMIAS)"was used to analyze Professor Li's medication rules and academic thoughts in treating oligoasthenospermia.Using network pharmacology methods,a comprehensive analysis of the targets and molecular mechanisms of the professor's core prescriptions for the treatment of this disease is carried out to provide a preliminary basis for subsequent further experimental studies.Method:The medical history of oligoasthenospermia that Professor Li Yueqing received from the Andrology Department of Dongzhimen Hospital from January 1,2019 to December 31,2019 was fully recorded.Two researchers independently entered data,established a database,and accurately input the data into the software.TCMIAS was used to conduct preliminary statistical analysis on the frequency of use of prescription drugs used by professors,the four qi and five flavors,and the meridian.At the same time,the software was used to calculate the association rules,prescription analysis,and new prescription analysis between drugs.Then the core prescription for the treatment of male oligoasthenospermia was obtained,and the clinical experience of the professor was also obtained.With the help of the online platforms of TCMSP and BATMAN,the active ingredients and potential targets of Chinese medicine in Zhonghe Yishen Seed Decoction were obtained,and the targets of male oligoasthenospermia were obtained through the online human Mendelian genetic database and GeneCards database.Using the above two target databases,a Venn diagram could be constructed to obtain the drug component target-the common target of male oligoasthenospermia.Using Cytoscape 3.6.1 software,a "compound-active ingredient-action target network" was established.The STRING database could perform protein interaction analysis on common targets.Cytoscape software was built the network diagram of protein interaction.Finally,with the help of DAVID database,GO and KEGG function enrichment analysis of common targets were performed.Result:(1)A total of 711 Chinese medicine prescriptions were included in this study,including 159 Chinese medicines.The frequency of occurrence of the medicines totaled 14,463 times,with an average of about 20 medicines per prescription.In traditional Chinese medicine,warm medicine is used most,followed by mild and cool medicines;sweet medicine is used most,bitterness and sourness are second,salty and astringent are the least.The meridians of the medicine mainly belong to the kidney and liver meridians,followed by lung,spleen and heart meridians.The statistics of drug frequency show that Professor Li Yueqing's commonly used drugs for the treatment of male oligoasthenospermia include raw rehmannia,rehmannia glutinosa,wolfberry,dodder,raspberry,schisandra,dogwood,achyranthes,astragalus,poria,eucommia,antler gum,plantain Seed,Morinda officinalis,Salvia miltiorrhiza,Dandelion,Polygonatum,Epimedium,Rhodiola,Cistanche,etc.According to the association rule algorithm,and after repeated confirmation with the professor,the composition of the basic prescription "Zhonghe Yishen Seed Decoction(ZHYSSD)" for the treatment of male oligospermia by Professor Li Yueqing:Raw Rehmannia 15g,Rehmannia Dlutinosa 15g,Cornus 12g,Dodder 15g,Lycium barbarum 15g,Plantago 12g,Raspberry 15g,Schisandra 10g,Raw Astragalus 30g,Antler Gum 10g,Salvia 15g,Dandelion 12g.Using the unsupervised entropy hierarchical clustering algorithm,4 new prescriptions and 4 core clustering prescription combinations were obtained.The innovative clinical medication model could be further optimized and applied according to the clinical practice.(2)Search the compound components of ZHYSSD in TCMSP and BATMAN and finally 199 potential core compounds were obtained,and 377 compounds were predicted to correspond to targets.Search for male oligospermia related targets in OMIM and GeneCards database,among which 528 oligospermia protein targets and 163 asthenospermia targets were obtained.After collecting the two data and removing duplication,the male oligospermia related targets were obtained.There are 651 points in total.Using Cytoscape to construct the Venn diagram of ZHYSSD potential targets and male oligoasthenospermia target data set,61 common targets were obtained.By constructing a ZHYSSD component-target network diagram and analyzing the topological structure of the constructed network,it is found that quercetin,luteolin,kaempferol,formononetin,and isorhamnetin can be considered as ZHYSSD exerting pharmacological activities Important compound.PPI network analysis could get the top ten potential core targets of ZHYSSD for the treatment of male oligoasthenospermia,including TP53,AKT1,SIRT1,ESR1,PTGS2,MAPK1,EGFR,TNF,CASP3,IL6.The GO analysis results suggested that ZHYSSD treatment of male oligoasthenospermia genetic biological process(BP)was significantly enriched in the response to organic cyclic compounds,the response to oxygenated compounds,the response to drugs,the response of cells to chemical stimuli,and the response to organic Substance reactions and other processes;cell components(CC)were mainly enriched in membrane rafts,membrane microdomains,membrane regions,inner membrane systems,cytoplasmic parts and other parts;in molecular function(MF),they were mainly enriched in the same protein binding,enzyme Binding,double-stranded DNA binding,tumor necrosis factor receptor superfamily binding,signal receptor binding.KEGG enrichment analysis revealed that the important signaling pathways related to ZHYSSD treatment of oligoasthenospermia include:HIF-1 signaling pathway,TNF signaling pathway,apoptosis pathway,p53 signaling pathway,NOD-like receptor signaling pathway,NF-?B signaling pathway,Toll-like receptor signaling pathway.Conclusion:1.Professor Li Yueqing's academic experience in treating male oligoasthenospermia:(1)The pathogenesis of oligoasthenospermia is imbalance between yin and yang,and the pathological changes are mainly kidney deficiency,combined with blood stasis and damp-heat;(2)Li Yue Professor Qing used medicines for the treatment of this disease to be more peaceful,and he also paid attention to the combination of cleansing and tonic,and the use of attack and tonic at the same time,to achieve the state of Yin and Yang secretion.2.Zhonghe Yishen Seed Decoction in the treatment of male oligoasthenospermia mainly exerted the characteristics of "multi-component-multi-target",and played a role in anti-oxidation,anti-inflammatory,and promoting proliferation and apoptosis.