AUTHOR=Wang Zaizhong , Cheng Lulu , Shang Zhigang , Li Zhihui , Zhao Yuping , Jin Wenwen , Li Yingyue , Su Fangchu , Mao Xiaobo , Chen Chuanliang , Zhang Jianhua 

TITLE=Network Pharmacology for Analyzing the Key Targets and Potential Mechanism of Wogonin in Gliomas

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.646187

DOI=10.3389/fphar.2021.646187

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> To analyze the key targets and potential mechanisms underlying the volatile components of <italic>Scutellaria baicalensis</italic> Georgi acting on gliomas through network pharmacology combined with biological experiments.</p><p><bold>Methods:</bold> We have extracted the volatile components of <italic>Scutellaria baicalensis</italic> by gas chromatography-mass spectrometry (GC-MS) and determined the active components related to the onset and development of gliomas by combining the results with the data from the Traditional Chinese Medicine Systems Pharmacology database. We screened the same targets for the extracted active components and gliomas through network pharmacology and then constructed a protein-protein interaction network. Using a Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we analyzed the protein effects and regulatory pathways of the common targets. Lastly, we employed ELISA and Western blot in verifying the key targets in the regulatory pathway.</p><p><bold>Results:</bold> We ultimately determined that the active component in <italic>S. baicalensis</italic> Georgi related to the onset and development of gliomas was Wogonin. The results of the network pharmacology revealed 85 targets for glioma and Wogonin. We used gene ontology to analyze these target genes and found that they involved 30 functions, such as phosphatidylinositol phosphokinase activation, while the KEGG analysis showed that there were 10 regulatory pathways involved. Through the following analysis, we found that most of the key target genes are distributed in the PI3K-Akt and interleukin 17 signaling pathways. We then cultured U251 glioma cells for the experiments. Compared with the control group, no significant change was noted in the caspase-3 expression; however, cleaved caspase-3 expression increased significantly and was dose-dependent on Wogonin. The expression of Bad and Bcl-2 with 25 μM of Wogonin has remained unchanged, but when the Wogonin dose was increased to 100 μM, the expression of Bad and Bcl-2 was noted to change significantly (Bad was significantly upregulated, while Bcl-2 was significantly downregulated) and was dose-dependent on Wogonin. The ELISA results showed that, compared with the control group, the secretion of tumor necrosis factor alpha, IL-1β, and IL-6 decreased as the Wogonin concentration increased. Tumor necrosis factor alpha downregulation had no significant dose-dependent effect on Wogonin, the inhibitory effect of 25 μM of Wogonin on IL-6 was not significant, and IL-1β downregulation had a significant dose-dependent effect on Wogonin.</p><p><bold>Conclusion:</bold> Wogonin might promote the apoptosis of glioma cells by upregulating proapoptotic factors, downregulating antiapoptotic factors, and inhibiting the inflammatory response, thereby inhibiting glioma progression.</p>