Mechanism of Dunhuang(敦煌)Medical Prescription Xiaobugan Decoction(小补肝汤)against Exercise-Induced Fatigue Based on Network Pharmacology and Experimental Validation
Objective:To investigate the effective components and possible mechanisms of Xiaobugan Decoction(小补肝汤)against exercise-in-duced fatigue by network pharmacology and experimental validation.Methods:The active components of Xiaobugan Decoction were searched in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The disease-related target genes were re-trieved from Genecards,Drugbank,Online Mendelian Inheritance in Humans(OMIM),and Pharmacogenetics and Pharmacogenomics Knowl-edge Base(PharmGkb).Venny2.1.0 was used to draw the Wayne diagram of the drug and disease targets,to obtain the intersection targets,which were imported into STRING for construction of the protein-protein interaction(PPI)network.High-throughput genomic sequencing was performed through Bioconductor and other online software,and the gene ontology(GO)annotation map and Kyoto gene and genome Encyclo-pedia(KEGG)enrichment pathway maps were obtained to predict the pathways involved.Animal experiments were carried out to validate the predictions of network pharmacology.Results:A total of 36 active components were screened,and 244 intersection targets were obtained.By the drug-component-target-disease network constructed,core components such as stigmasterol,kadsurenone,beta-sitosterol,hancinone C and taxifolin were screened.Eleven key targets,including AKT1,GNAQ,and PTGS2,were screened through PPI network.GO enrichment analy-sis yielded 3 675 biological processes(including responses to drugs,oxygen content,and hypoxia),379 cellular components(including mem-brane rafts,membrane microregions,and mitochondrial outer membrane),and 624 molecular functions(including DNA-transcription factor binding,ubiquitin-protein ligase binding,and G-protein-coupled amine receptor activity).KEGG enrichment analysis found that the main sig-naling pathways involved were calcium signaling pathway(GNAQ-PLCB2-IP3R1-CAM),cAMP signaling pathway,thyroid hormone signaling pathways,etc.The animal experiments showed,compared with the conditions in normal control group,the exhaustion time in weight-bearing swimming was reduced in model control group,and lactate(LD)and urea nitrogen(BUN)in serum was increased,while liver glycogen and myoglycogen were decreased(P＜0.01),additionally,there was disordered and uneven arrangement of the skeletal muscle cells and high infil-tration of inflammatory cells,and the protein expressions of GNAQ,PLCB2,IP3RI and CAM in skeletal muscle were up-regulated(P＜0.01).Compared with the model control group,the administration groups had increased exhaustion time in weight-bearing swimming(P＜0.01),re-duced LD and BUN in serum(P＜0.05),elevated liver glycogen and myoglycogen(P＜0.05),furthermore,the arrangement of the skeletal muscle fibre in administration groups was improved,with reduced inflammation(P＜0.05),and the protein expressions of GNAQ,PLCB2,IP3RI,and CAM in skeletal muscle tissue were down-regulated(P＜0.05).Conclusion:Xiaobugan Decoction can inhibit the protein expres-sions of GNAQ,PLCB2,IP3RI and CAM in skeletal muscle tissues of exercise-induced mice,thus regulating the intracellular calcium ions and alleviating the fatigue due to the disruption of mitochondria and sarcoplasmic reticulum caused by calcium overload.
Xiaobugan Decoction(小补肝汤)Network pharmacologyExercise-induced fatigueGuanine nucleotide-binding protein q poly-peptideCalcium ion
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