Professor Yang Xiaohui's Prescription Rules And Network Pharmacology Research On The Treatment Of Type 2 Diabete

Objective:1.To analyze the medication pattern of Professor Yang Xiaohui in treating patients with type 2 diabetes using the "TCM Heritage Assist Platform V3.0" software,to explore the core drugs and their compounding methods,to summarize Professor Yang Xiaohui’s medication experience,and to derive the core prescriptions.2.Using the network pharmacology method,we analyzed the potential key targets and pathways of the core prescriptions to intervene in type 2 diabetes,and explored their mechanisms of action to provide partial evidence to support rational clinical use and new drug development.Methods:1.Case and prescription data were collected from patients with type 2 diabetes mellitus attending the International Department of Dongzhimen Hospital,Beijing University of Traditional Chinese Medicine and the outpatient clinic of Director Yang Xiaohui of Oriental Hospital between January 2019 and November 2022.The data were screened,sorted and standardized according to the inclusion and exclusion criteria,and the processed data were entered into the "TCM Heritage Auxiliary Platform V3.0" software,analyzed in terms of medicinal properties,taste,attribution,and dosage,etc.,explored the rules of formula formation through association rules,mined potential new prescriptions based on cluster analysis,and finally identified the core prescriptions after interview with Professor Yang Xiaohui.The core prescriptions were identified after the interview with Professor Yang Xiaohui.2.The main active ingredients and targets of each drug in the core prescription were screened through the TCMSP database,and the information was standardized using the Uniprot protein database.The keywords "T2DM","type 2 diabetes mellitus" and "type 2 diabetes" were used to search OMIM The potential targets related to diabetes in OMIM database,Drug Bank database,TTD database and GeneCards database were compared and de-duplicated with the core prescription targets to obtain the core prescription-disease common targets,and the common targets were imported into STRING database to build PPI network.Metascape platform was used to perform GO functional enrichment analysis and KEGG signaling pathway analysis.Finally,CytoScape 3.9.1 was used to visualize and construct the "prescription-drug-component-disease-target-pathway" network.Results:1.A total of 155 cases were included in this study,of which 43.87%were female and 56.13%were male;the youngest age was 25 years old and the oldest was 88 years old,with an average age of 57.8 years old,mainly distributed in the age group of 40-69 years old.The top three most frequent clinical comorbidities were hypertension,hyperlipidemia,and coronary atherosclerotic heart disease.The top three symptoms with the highest frequency were:weakness,poor sleep,and foam in urine.The results of symptom analysis showed that the deficiency symptoms were mostly Qi and Yin deficiency,Liver and Kidney Yin deficiency,and Spleen Qi deficiency,with 89,22,and 19 occurrences,respectively;the actual symptoms were mostly Qi stagnation,Qi stagnation and heat,and blood stasis,with 41,38,and 33 occurrences,respectively.2.Among the 155 prescriptions,the top 10 most frequently used herbs and the commonly used doses were Huanglian 15 g,Chishao 20 g,Chaihu 10 g,Baihe 20 g,Niuxi 15 g,Chantui 10 g,Puhuang 15 g,Zhimu 20 g,Sangjisheng 12 g,and Sangzhi 15 g.The pharmacological effects statistics showed that the commonly used drugs were mainly heat clearing,deficiency tonifying,and symptomatic drugs.The top three pharmacological properties were cold(47.06%),warm(26.86%)and flat(21.76%)drugs in descending order;the top three pharmacological tastes were bitter(39.22%),sweet(30.90%)and pungent(18.88%)in descending order;the top three meridians were liver,lung and spleen meridians in descending order.3.The analysis of association rules showed that "Huanglian-Chishao","Chishao-Chaihu","Huanglian-Chaihu","Huanglian-Niuxi ","Huanglian-Baihe","Zhiwu->Huanglian","Huanglian,Puhuang->Chantui",and "Chaihu->Chishao","Huanglian,Chaihu->Chishao","Chantui,Puhuang->Huanglian","Niuxi->Huanglian".After interviewing Professor Yang Xiaohui,the core prescriptions were set as "Huanglian,Chaihu,Chishao,Baihe,Zhimu and Niuxi".4.The core prescriptions were analyzed by network pharmacology,and 84 active ingredients were obtained,mainly quercetin,kaempferol,stigmasterol,beta-sitosterol and baicalein.Among them,28 active ingredients had no corresponding target proteins,and the remaining 56 active ingredients corresponded to a total of 220 targets.1991 type 2 diabetes targets were obtained by taking intersection with drug targets to obtain 157 core targets,including AKT1,IL6,TNF,TP53,VEGFA,CASP3,IL1B,PTGS2,ESR1,PPARG,etc.GO analysis The results showed that core prescriptions have an influence in biological processes such as response to hormones,response to inorganic substances,response to xenobiotic stimuli,and response to nutrient levels;may be involved in cellular composition such as membrane rafts,receptor complexes,transcriptional regulator complexes,and vesicle luminal bodies;and are molecularly bound to DNA-binding transcription factors,protein domain-specific binding,protein homogenization activity,and adrenergic receptor activity The results of KEGG analysis showed that the main pathways of core prescription intervention are AGE-RAGE signaling pathway,PI3K-Akt signaling pathway and PPAR signaling pathway,which exert their therapeutic effects by regulating glucolipid metabolism,improving insulin resistance,reducing oxidative stress,reducing inflammatory response,inhibiting gluconeogenesis and promoting glucose uptake.Conclusion:1.Professor Yang Xiaohui’s treatment of type 2 diabetes attaches importance to the important role of qi and blood in the pathogenesis.He uses drugs to enter the liver,spleen and lung meridians,aiming to regulate the qi flow;he uses cold and warm to clear heat without harming the righteousness and to nourish deficiency without helping the evil.The treatment focuses on the basic pathogenesis of "yin deficiency and dry heat",regulating Qi and Blood together and taking into account the actual evil such as qi-depression,phlegm-dampness and blood stasis.The core drug composition is Huanglian,Chaihu,Chishao,Baihe,Zhimu and Niuxi.In this formula,Huanglian,Chaihu and Chishao clear heat,move Qi and invigorate Blood,Baihe and Zhimu clear Yin,and Niuxi tonifies Yin of Liver and Kidney.2.The core prescription was studied by the method of network pharmacology,and the results showed that the core prescription intervened and regulated type 2 diabetes through multi-component,multi-target and multi-pathway synergy,and the main chemical components screened were quercetin,kaempferol,dousterol,β-sitosterol and baicalin.The core action targets are AKT1,IL6,TNF,TP53,VEGFA,etc.Through regulating AGE-RAGE,PI3K-Akt,PPAR and other signaling pathways,it exerts its therapeutic effects in glucolipid metabolism,improving insulin resistance,reducing oxidative stress,alleviating inflammatory response,inhibiting gluconeogenesis,and promoting glucose uptake.