Traditional processing unlocks anti-atherogenic potential of perilla fruit via PPAR-γ activation by luteolin

Abstract

The accumulation of foam cells, lipid-laden macrophages in atherosclerotic plaques, is a hallmark of cardiovascular disease progression. These cells contribute to chronic inflammation and plaque instability, underscoring the need for novel therapeutic strategies. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a nuclear receptor pivotal to lipid metabolism and inflammation control. Traditional Chinese Medicine (TCM) processing techniques, such as stir-frying, are believed to enhance herb efficacy, yet the molecular basis remains insufficiently understood. Here, we demonstrate that stir-fried Perilla fruit significantly increase luteolin content-a flavonoid compound capable of binding PPAR-γ at key residues (SER289, HIS323, PHE360, TYR473) as validated by molecular docking and dynamics simulation. In ox-LDL-induced RAW264.7 macrophages, luteolin promoted cholesterol efflux, reduced lipid accumulation, and upregulated PPAR-γ pathway proteins, effects that were abolished by the antagonist GW9662. These results provide mechanistic insight into the enhanced efficacy of stir-fried Perilla and highlight luteolin as a promising natural compound for atherosclerosis prevention.

Keywords

Perilla fruit / PPAR-γ / Traditional chinese medicine processing / Lipid regulation / Foam cell

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Funding

Tianjin Research Innovation Project for Postgraduate Students(2022kj159)

RIGHTS & PERMISSIONS

The Author(s)