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

## TL;DR

Stir-frying Perilla fruit increases luteolin, which activates PPAR-γ and helps reduce atherosclerosis risk by improving cholesterol and inflammation.

## Contribution

The study reveals how traditional processing enhances luteolin content in Perilla fruit, linking it to PPAR-γ activation and anti-atherogenic effects.

## Key findings

- Stir-fried Perilla fruit has higher luteolin levels that bind to PPAR-γ at specific residues.
- Luteolin promotes cholesterol efflux and reduces lipid accumulation in macrophages via PPAR-γ.
- PPAR-γ activation by luteolin is blocked by the antagonist GW9662, confirming its mechanism.

## 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.

The online version contains supplementary material available at 10.1186/s40643-025-00957-7.