Abstract
Luteolin, a natural flavone compound, exists in a variety of fruits and vegetables, and its anticancer effect has been shown in many studies. However, its use in glioma treatment is hampered due to the fact that the underlying mechanism of action has not been fully explored. Therefore, we elucidated the potential antiglioma targets and pathways of luteolin systematically with the help of network pharmacology and molecular docking technology. The druggability of luteolin, including absorption, excretion, distribution, and metabolism, was assessed via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The potential targets of luteolin and glioma were extracted from public databases, and the intersecting targets between luteolin and glioma were integrated and visualized by a Venn diagram. In addition, GO and KEGG pathway analysis was engaged in Metascape. The network of the luteolin-target-pathway was visualized by Cytoscape. Ultimately, the interactions between luteolin and predicted key targets were confirmed by Discovery studio software. According to the ADME results, luteolin shows great potential for development into a drug. 4860 glioma-associated targets and 280 targets of luteolin were identified, of which 205 were intersection targets. 6 core targets of luteolin against glioma, including AKT1, JUN, ALB, MAPK3, MAPK1, and TNF, were identified via PPI network analysis of which AKT1, JUN, ALB, MAPK1, and TNF harbor diagnostic value. The biological processes of luteolin are mainly involved in the response to inorganic substances, response to oxidative stress, and apoptotic signaling pathway. The essential pathways of luteolin against glioma involve pathways in cancer, the PI3K-Akt signaling pathway, the TNF signaling pathway, and more. Meanwhile, luteolin's interaction with six core targets was verified by molecular docking simulation and its antiglioma effect was verified by in vitro experiments. This study suggests that luteolin has a promising potential for development into a drug and, moreover, it displays preventive effects against glioma by targeting various genes and pathways.
Highlights
Glioma is the most common and malignant brain tumor, with more than 10,000 cases diagnosed per year and a fiveyear survival rate of only 5% [1]. e current standard of therapy is surgery coupled with adjuvant radiotherapy and chemotherapy with temozolomide (TMZ) that can be combined with intermediate-frequency alternating electric field therapy, if necessary [2, 3]
By employing the TCMSP database with the search term “luteolin,” we investigated its pharmacokinetic properties
Luteolin was studied via TCMSP to analyze its ADME characteristics (Table 1)
Summary
Glioma is the most common and malignant brain tumor, with more than 10,000 cases diagnosed per year and a fiveyear survival rate of only 5% [1]. e current standard of therapy is surgery coupled with adjuvant radiotherapy and chemotherapy with temozolomide (TMZ) that can be combined with intermediate-frequency alternating electric field therapy, if necessary [2, 3]. E current standard of therapy is surgery coupled with adjuvant radiotherapy and chemotherapy with temozolomide (TMZ) that can be combined with intermediate-frequency alternating electric field therapy, if necessary [2, 3] This treatment does not significantly change survival time, and the median overall survival is still approximately 15 months [4]. Natural products have shown a wide range of pharmacological or biological activities, rendering them potential candidates of treatment strategies against central nervous system diseases such as neurological disorders, neurodegenerative diseases, and tumors [6, 7]. Its potential mechanism of action on glioma cells remains unclear and needs further elucidation
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