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Exploring the Antiglioma Mechanisms of Luteolin Based on Network Pharmacology and Experimental Verification
Renxuan Huang1, Rui Dong2, Nan Wang1
1Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
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.
Insights
Luteolin, a natural compound found in plants, shows promise for treating glioma by targeting key pathways like PI3K-Akt. This study identified core targets and confirmed its potential as an anticancer drug.
Area of Science:
- Pharmacology and Bioinformatics
- Oncology
- Natural Products Chemistry
Background:
- Luteolin, a flavone from fruits and vegetables, exhibits anticancer properties.
- The precise mechanisms of luteolin's action against glioma remain underexplored.
- Understanding these mechanisms is crucial for developing luteolin as a glioma therapeutic.
Purpose of the Study:
- To systematically identify potential anti-glioma targets and pathways of luteolin using network pharmacology.
- To assess the druggability and molecular interactions of luteolin with key targets.
- To validate the anti-glioma effects of luteolin through computational and experimental methods.
Main Methods:
- Network pharmacology was employed to predict luteolin's targets and pathways against glioma.
- Databases like TCMSP, public target repositories, and Metascape were utilized.
- Molecular docking and in vitro experiments validated luteolin's interactions and efficacy.
Main Results:
- Luteolin demonstrated favorable pharmacokinetic properties (ADME).
- 205 intersecting targets between luteolin and glioma were identified, with 6 core targets including AKT1, JUN, ALB, MAPK1, and TNF.
- Luteolin's mechanisms involve response to inorganic substances, oxidative stress, apoptosis, and pathways in cancer, PI3K-Akt, and TNF signaling.
Conclusions:
- Luteolin exhibits significant potential as an anti-glioma drug candidate.
- The study elucidated luteolin's molecular targets and pathways, supporting its therapeutic development.
- Luteolin shows promise for glioma prevention and treatment through multi-target and multi-pathway mechanisms.
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