Based On Data Mining And Network Pharmacology,to Study Professor Lin Shouning’s Medication Law And Mechanism In The Treatment Of Diarrhea Irritable Bowel Syndrome

Objective: To summarize the dosing pattern of Professor Lin Shouning’s treatment of diarrheal irritable bowel syndrome(IBS-D)based on data mining analysis,and to excavate the core prescription drugs and further elaborate their mechanism of action through network pharmacology and molecular docking techniques.Methods: By collecting outpatient prescriptions of IBS-D patients who met the inclusion criteria from the outpatient clinic of Rui Kang Hospital affiliated to Guangxi University of Traditional Chinese Medicine(September2012-September 2022)and collecting patients’ basic information,the imported data were analyzed by relying on the software of "Traditional Chinese Medicine Inheritance Support System Platform(V3.0)".The basic information(gender,age)statistical analysis,Traditional Chinese Medicine evidence analysis,drug performance analysis,drug frequency analysis,association analysis and clustering analysis were performed on the imported data,and Professor Lin Shouning’s prescriptions for IBS-D were extracted,and his clinical experience in treating IBS-D was further summarized by combining his learning experience with his teachers.And based on the results of drug frequency analysis,those with drug frequency ≥ 80% were used as core prescription drugs.Based on the obtained core prescriptions,active ingredients were predicted by TCMSP,BATMAN-TCM,Drug Bank,Chinese medicine and chemical composition database databases and literature review,drug targets were predicted by Swiss Target Prediction database,and IBS-D disease targets were predicted by Gene Card database;Drug targets and IBS-D disease targets were intersected through Venn Diagram online website,and the intersected targets were analyzed by DAVID database for GO and KEGG enrichment,and by STRING database for PPI analysis,and the results were imported into Cytoscape 3.7.2 software and selected as core targets using"cyto Hubba "plug-in" to select the top five targets in terms of Degree value as core targets;Based on Cytoscape 3.7.2 software,a "core formula-active ingredient-target-disease" network was constructed,and the top five active ingredients in terms of Degree were selected as the core ingredients;the core targets and core active ingredients were docked by Autodock vina software.Results:(1)In this study,information and first prescriptions were collected from 645 patients,including 309 males and 336 females,with a male-to-female ratio of approximately 1:1.09,and the age of onset mainly concentrated in 30-59 years;The distribution of TCM evidence is from high to low: dampness in the bowels,liver depression and spleen deficiency,spleen and stomach weakness,dampness and heat,cold and dampness in diarrhea,and deficiency of kidney yang;A total of 149 herbal medicines are involved,most of which are mainly qi-regulating,deficiency-supplementing,damp-transforming and food-eliminating medicines,which are mostly warm,calm and cold in nature,with sweet,pungent and bitter flavors,and with spleen,stomach,lung,liver and kidney meridians as the main channels;Drugs used more frequently are: Fuling,Chenpi,Sharen,Muxiang,Jineijin,Gancao,Baizhu,etc.;Commonly used pairs of drugs are: Fuling-Chenpi,Fuling-Sharen,Chenpi-Sharen,etc.Among the rules of medication for each type of evidence,the core drugs for dampness in the intestinal organs are Chenpi,Baizhu,Sharen,Fuling,Cangzhu,Muxiang,Jineijin,Gancao,Maiya,Yiyiren,Diyu,Huaihua,and Foshou;The core drugs for the liver-depression and spleen-deficiency syndrome are Baishao,Chenpi,Baizhu,Sharen,Fuling,Muxiang,Jineijin,Gancao,Maiya,Yanhusuo,and Haipiaoxiao;The core medicines for the evidence of weakness of the spleen and stomach are Chenpi,Baizhu,Sharen,Fuling,Muxiang,Jineijin,Gancao,Maiya,and Yiyiren;The core medicines for the evidence of internal damp-heat are Chenpi,Baizhu,Sharen,Fuling,Jineijin,Gancao,Muxiang,Maiya,Huanglian,Cangzhu and Diyu;The core medicines for cold-damp diarrhea evidence are Chenpi,Baizhu,Fuling,Dafupi,Baizhi,Banxia,Gancao,Houpo,Jiegeng,Zisu and Huoxiang;The core medicines for the evidence of kidney yang deficiency are Baizhu,Fuling,Wuweizi,Buguzhi,Wuzhuyu,Roudoukou,Dangshen and Gancao.(2)The results of the network pharmacological analysis showed that the core ingredients of the core formula for the treatment of IBS-D were Cerevisterol、naringenin、Eburicoic Acid、Hesperetin and hederagenin;The core targets were IL6,TNF,EGFR,VEGFA and SRC;Mainly enriched in signaling pathways related to PI3K-AKT signaling pathway,AGE-RAGE signaling pathway(diabetic complications),human cytomegalovirus infection-related signaling pathway,Rap1 signaling pathway and JAK-STAT signaling pathway;The molecular docking results showed that the binding energies of both core components and core targets were less than-5.0kcal/mol,suggesting that the predicted results of this study are more reliable.Conclusions:(1)Through prescription data mining,we found that Professor Lin Shouning’s clinical treatment of IBS-D was based on the main method of dampness management,and the basic principle of "connecting the Qi of the internal organs and removing dampness".Pay attention to the elevation of the spleen and stomach qi,the treatment should be to strengthen the spleen and dispel dampness,move qi and relieve pain.Most of the selected herbs are mainly for regulating qi,tonifying the spleen and stomach,eliminating food and removing stagnation.Commonly used therapeutic formulas are Changbingfang,Tongxie Yaofang,Shenling Baizhu San,Decoction of Xiexin and Decoction of Lianpu,Huoxiang Zhengqi San,and Sishen Wan plus or minus.(2)The present study revealed through network pharmacology and molecular docking technique analysis that the active active ingredients such as Cerevisterol 、 naringenin 、 Eburicoic Acid 、 Hesperetin and hederagenin elements in the core formula for the treatment of IBS-D work by modulating the core targets such as IL6,TNF,EGFR,VEGFA and SRC,which in turn regulate the PI3K-AKT signaling pathway,AGE-RAGE signaling pathway(diabetic complications),human cytomegalovirus infection-related signaling pathway,Rap1 signaling pathway and JAK-STAT signaling pathway,and other related signaling pathways,thus acting.