Effects of Asiatic acid on brain cancer by altering astrocytes and the AKT1-PRKCB signaling pathway: A genomic and network pharmacology perspective

The most common primary brain tumor, glioblastoma (GBM), currently has a dismal prognosis because of its fast growth and dissemination. Recent research indicates that Asiatic acid (AA), which is extracted from Trema orientalis L., has potential as a medicinal agent. AA, which was obtained from a methanolic extract of Trema orientalis L. and examined utilizing high-resolution mass spectroscopy (HRMS) analysis, was employed in this investigation. Then, in order to forecast the therapeutic advantages of AA in managing GBM, we conducted an in silico study. Online web servers like SwissADME, pKCSM, and Protox-II were used to assess AA. Then, the major targets of the AA (from Swiss Target Prediction and TargetNet) and GBM (from GeneCards and DisGeNET) were identified. The important genes were then merged into the STRING and ShinyGo databases to examine the protein–protein interaction (PPI) network, gene annotation, and KEGG pathways, with the goal of identifying the core mechanisms involved in GBM management. The top five hub gene targets of the built network (AKT1, SRC, IL-6, TNF, and EGFR) were investigated, along with some contemporaneous additional major targets (PRKCB, GSK3B, ITGB1, BRAF, and PTPN6). These targets were tightly linked to GO activities such as synoviocyte proliferation, cytokine activity, and EGFR tyrosine kinase inhibitor resistance, as well as proteoglycans in cancer-related pathways. Furthermore, a survival study was conducted to assess the chronicity of targets, as well as molecular docking activity between important targets and AA against GBM to determine binding effectiveness. Overall, the study found that AKT1 is the most powerful receptor for AA, having a binding energy of −8.19 kcal/mol, followed by PRKCB (−7.53 kcal/mol). Finally, docking studies suggest that AA has the potential to be an effective treatment for GBM. Furthermore, clinical studies will provide more precise insights into the AA’s efficacy as a medicine in the future.