Network Pharmacology Analysis of Molecular Mechanism of Curcuma longa L. Extracts Regulating Glioma Immune Inflammatory Factors: Implications for Precise Cancer Treatment.

Introduction: Curcuma longa L. has been associated with different antioxidant, antiinflammatory, bactericidal and anticancer effects, but the mechanisms of the effects are not yet clearly understood. This study aimed to investigate the key targets and the effect of potential molecular mechanisms of Curcuma longa L. extracts on glioma using different network pharmacology analysis approaches.

Methods: The components of Curcuma longa were extracted by gas chromatography-mass spectrometry (GC-MS), and the active components related to the occurrence and development of glioma were determined by traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database, and the same targets of the active components and glioma were screened by network pharmacology approach. Then, the protein's function and regulatory pathway of the common targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The protein's action and regulatory pathway of the common targets were analyzed with the Cytoscape package using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to construct the target interaction network through which the key targets were identified.

Results: GC-MS combined with TCMSP database was used to identify the active components related to the occurrence and development of glioma in Curcuma longa. Finally, we identified the active components 1-(1,5-Dimethyl-4-hexenyl)-4-methyl benzene and Zingiberene. At the same time, 190 target genes of Curcuma longa extracts on glioma were obtained using the Venn diagram. The results of GO analysis showed that the biological processes involved included a response to stimulation, metabolic process, inflammatory process, cell differentiation, and regulation of biological processes. KEGG analysis showed that the PI3K-Akt signaling pathway, MAPK signaling pathway, Th17 cell differentiation, and proteoglycan pathway might be involved in cancer. Further analyses showed that the IL-17 signaling pathway and Interleukin-4 and interleukin-13 signaling were involved in the inflammatory pathway. The analysis of key nodes showed that GSK3B, MAPK14, HSP90AA1, MAPK3 and MAPK8 were IL-17 signaling pathways, while HIF1A and JAK3 were Interleukin-4 and interleukin-13 signaling pathways.

Conclusion: Curcuma longa extracts can regulate the occurrence and development of glioma by regulating the immune-inflammatory responses.