Study On The Molecular Mechanism Of Baicalein Inhibiting Glioblastoma Based On Network Pharmacology

Background and objectiveGlioma is the most common primary tumor of central nervous system,accounting for more than 40%of intracranial tumors.According to the classification of the World Health Organization,gliomas can be classified into Ⅰ-Ⅳ grades,among which type Ⅳ gliomas,also known as glioblastoma(GBM).After receiving the standard STUPP regimen,only 3%to 5%of GBM patients have a median survival time of more than 3 years.It has been found that some patients with GBM can be treated with traditional Chinese medicine to improve their clinical symptoms during adjuvant chemotherapy.Therefore,we consider whether there are effective pharmaceutical ingredients in traditional Chinese medicine prescriptions that may inhibit the progression of glioblastoma.In this study,Xuefu Zhuyu decoction(XFZYD),a classic Chinese medicine prescription,was selected as the research object.Through the pseudonetwork pharmacology combined with the bioinformatics analysis of glioblastoma,to explore whether there are some traditional Chinese medicine ingredients that can inhibit the growth of glioblastoma cells.Materials and methodsCombining pharmacological data,second-generation sequencing data,pharmacokinetic parameters and new node importance calculation method,a new network pharmacological strategy was designed to decipher the potential therapeutic mechanism of XFZYD on GBM.Gene ontology database(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)database were used to analyze the pathway of core component groups(CCG)in XFZYD in glioblastoma.Some components of CCG were verified by in vitro experiments.P<0.05(bilateral)indicates that the difference is statistically significant.ResultWe identified 117 chemical constituents through ADME screening,and then construct a weighted pathological gene network and component-target network(C-T network)and integrate the two networks through PPI data to establish a comprehensive component-target-pathogenic gene network(C-T-P network),Pagerank algorithm is used to screen the C-T-P network,and the results show that the enrichment pathway of targets in key functional networks can cover 77.92%of the enrichment pathway of pathogenic genes.A new calculation model of cumulative contribution rate(CCR)is designed,and 21 screened components were named CCG.Some core components of CCG were verified by in vitro experiments.The results show that our strategy of CCG and inferring potential mechanism has good reliability and accuracy.The results show that CCG can treat GBM by targeting PI3K-Akt signaling pathway and Toll-like receptor signaling pathway.Further experiments in vitro proved that baicalein and wogonin in CGG can inhibit the proliferation of GBM and promote apoptosis.ConclusionAt present,our network pharmacology model provides a powerful tool for optimizing the core component groups and decoding the underlying mechanism of TCM prescriptions.There are still some limitations.For example,in animal medical research of XFZYD,how to select less active ingredients,and verify its therapeutic effect and molecular mechanism of GBM through in vivo experiments.