Targeting Autophagy with Geniposide Ameliorates Atherosclerosis in [Formula: see text] Mice

Area of Science:

• Cardiovascular Research
• Pharmacology
• Cell Biology

Background:

• Atherosclerosis (AS) is a leading global cause of mortality.
• Geniposide (GP), known for lipolytic and anti-inflammatory effects, is used for cardiovascular diseases.
• Autophagy plays a critical role in cardiovascular health, and GP's mechanism in AS requires elucidation.

Purpose of the Study:

• To investigate the underlying mechanism of Geniposide (GP) in ameliorating atherosclerosis (AS).
• To determine if GP regulates autophagy via the PI3K/Akt/mTOR pathway to treat AS.

Main Methods:

• Network pharmacology and molecular docking were used for preliminary mechanism prediction.
• Oil Red O, Sirius Red, Masson's trichrome staining, and immunohistochemistry were employed.
• Western blotting (WB) and immunofluorescence (IF) assessed protein levels related to autophagy and the PI3K/Akt/mTOR pathway.

Main Results:

• GP inhibited atherosclerotic lipid accumulation and stabilized plaques.
• GP reduced macrophage infiltration, indicated by decreased F4/80 expression.
• GP promoted autophagy by increasing LC3 and Beclin1, decreasing P62, and inhibiting PI3K/Akt/mTOR phosphorylation.

Conclusions:

• Geniposide (GP) effectively treats atherosclerosis (AS).
• GP enhances autophagy through the PI3K/Akt/mTOR pathway.
• GP demonstrates therapeutic potential for cardiovascular disease by targeting AS mechanisms.