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Luteolin alleviates inflammation by inhibiting the PI3K-Akt-FOXO3a pathway
Leyuan Zeng1, Jinxian Lu1, Ronghua Liu1
1Jiangxi University of Chinese Medicine, 1688 Meiling, Nanchang, 330004, Jiangxi, P. R. China.
Naunyn-Schmiedeberg'S Archives of Pharmacology
|July 22, 2026
Summary
Luteolin, a plant flavonoid, reduces inflammation by targeting the PI3K/Akt/FOXO3a pathway. This study confirms luteolin
Area of Science:
- Molecular Biology
- Pharmacology
- Immunology
Background:
- Luteolin, a natural flavonoid, exhibits diverse biological activities.
- Its precise molecular mechanisms for anti-inflammatory effects are not fully understood.
- Network pharmacology predicted involvement of the PI3K/Akt/FOXO3a pathway.
Purpose of the Study:
- To elucidate the molecular mechanism of luteolin's anti-inflammatory properties.
- To investigate luteolin's interaction with the PI3K/Akt/FOXO3a signaling cascade.
Main Methods:
- Computational methods: Network pharmacology, molecular docking, and molecular dynamics simulations.
- In vitro experiments: LPS-stimulated RAW264.7 macrophages.
- Biochemical assays: Western blotting, cellular thermal shift assay (CETSA), isothermal dose-response, and drug affinity response target stability (DARTS).
Main Results:
- Luteolin significantly reduced the phosphorylation of PI3K, Akt, and FOXO3a in macrophages.
- Computational simulations predicted stable binding of luteolin to PI3K, Akt, and FOXO3a.
- Experimental assays confirmed direct interaction between luteolin and PI3K.
Conclusions:
- Luteolin exerts anti-inflammatory effects by modulating the PI3K/Akt/FOXO3a pathway.
- Direct interaction with PI3K is a key mechanism underlying luteolin's action.
- Findings support luteolin's therapeutic potential for inflammatory conditions.
