Based On Data Mining And Network Pharmacology To Explore The Mechanism Of Maxingkugan Decoction In The Treatment Of Northwest Pulmonary Epidemic

Objective Data mining,network pharmacology and in vivo experiments were used to explore the mechanism of MXKG Decoction in the treatment of pulmonary epidemic in northwest China,so as to provide a reference for further guiding clinical diagnosis and treatment and drug research and development.Methods 1.The ancient and modern prescriptions for the treatment of pulmonary epidemic were collected by the Dictionary of Traditional Chinese Medicine Prescriptions,the encyclopaedia of TCM and CNKI literature resources,and the frequency analysis,nature,flavours,channel tropism,efficacy and the association rules among drugs were analyzed by the software of the traditional Chinese medicine inheritance computing system V3.0.,Summarize the medication rule of pulmonary disease,and confirm that the production and treatment of Maxingkugan(MXKG)decoction is in line with the general law of pulmonary system epidemic disease medication.2.The active compounds and their targets of MXKG Decoction were obtained from TCMSP and Gene Cards,and the main targets of pulmonary diseases were obtained from Genecards.The PPI network model was constructed in STRING and Cytoscape v3.9.1 software,and the GO and KEGG pathways of intersecting targets were analyzed in Metascape.Cytoscape v3.9.1 software was used to construct the "component-disease-pathway" network diagram,and finally Auto Dock-Vina software was used for molecular docking.3.Lps-induced ALI was performed in vivo.Male C57BL/6 mice were divided into control group(5mg/kg normal saline),model group(5mg/kg LPS)and administration group(15.28g/kg MXKG).Model group and administration group were intraperitoneally injected with LPS 5mg/kg,respectively,while control group was injected with physiological saline.The levels of IL-6,IL-1β and TNF-α in BALF were determined by ELISA.H&E staining was used to observe the pathological morphology of mouse lung tissue.The expression of p-AKT in mouse lung tissue was detected by immunohistochemistry(IHC).The expression levels of PI3K/AKT signaling pathway related proteins(p-PI3 K,PI3K,p-AKT,and AKT)and apoptosis-related proteins(Bax,Cleaved Caspase-3,and Bcl-2)were detected by Western Blot(WB).Results 1.A total of 855 prescriptions were screened for the treatment of pulmonary epidemic.The results showed that licorice,bitter almond and ephedra ranked the top three high-frequency drugs,and the drug efficacy was mainly clearing heat and detoxifying,evacuating wind and heat.The medicinal properties were mainly cold,mainly bitter and pungent.The main syndromes are epidemic virus syndrome with lung meridian as the core.2.According to the epidemic characteristics and transmission rules of cold dryness in the northwest lung system,MXKG decoction composed of Radix bupleurum silver and Radix sophora flavescens was selected as the research object based on Sanao Decoction.2.The main active components of MXKG Decoction in the treatment of pulmonary blight are quercetin,formononetin,kaempferol,luteolin,naringin,isorhamnetin,medinesin,licorice chalcone A,stigmasterol,etc.The core targets are: AKT1,TNF,IL6,TP53,VEGFA,JUN,IL-1β,CASP3,STAT3,HIF-α,MAPK,PTGS2,etc.It is mainly enriched in PI3K-AKT signaling pathway,ILL-17 signaling pathway,TNF signaling pathway and MAPK signaling pathway.Molecular docking assay showed that 68% of the active ingredients were tightly bound to the target proteins.3.In vivo experiments.(1)ELISA results showed that the expression levels of IL-6,IL-1β and TNF-α in model group and MXKG group were significantly higher than those in control group(p< 0.05),the expressions of all inflammatory factors in MXKG group were significantly lower than those in model group(p<0.05);(2)HE staining showed that compared with model group,the lung tissue structure in MXKG group was relatively complete,and inflammatory cell infiltration in alveolar cavity was reduced.(3)IHC results showed that the expression of p-AKT in MXKG group was decreased compared with model group.(4)The PI3K-AKT pathway gene was detected by WB and it was found that the p-PI3K/PI3 K ratio in the model group was higher than that in the control group(p<0.05),the protein expression of p-PI3 K and p-AKT in MXKG group was decreased compared with model group,and the ratio of p-PI3K/PI3 K and p-AKT/AKT was decreased,with statistical significance(p<0.05).Finally,WB was used to detect apoptosis-related proteins.cleaved caspase-3 and Bax protein levels were reduced in the MXKG group(p<0.05)and increased Bcl-2 protein level(p<0.05).Conclusion 1.The main drugs used for pulmonary diseases are clearing heat,relieving surface,eliminating phlegm,relieving cough and relieving asthma.Sanao Decoction,the core prescription,can be used as a reasonable choice of drugs for the treatment of pulmonary diseases based on TCM clinical syndrome differentiation,and play the role of promoting lung,relieving surface and relieving asthma.The prescription rules of northwest pulmonary cold dry disease and pulmonary disease have some similarity;2.In the treatment of pulmonary epidemic,MXKG Decoction is mainly involved in PI3K-AKT and other inflammatory pathways,regulating the response mechanism of inflammation,oxidative stress,and apoptosis,and playing anti-inflammatory,so as to improve lung function.3.MXKG Decoction can inhibit the secretion of inflammatory factors IL-1β,IL-6 and TNF-α in ALI,down-regulate the expression of p-AKT,inhibit the activation of PI3K-AKT signaling pathway,reduce the expression of various cytokines Bax and cleaved-caspase-3,and up-regulate the expression of Bcl-2 protein,so as to inhibit apoptosis and play an anti-inflammatory role.Improve lung tissue damage.