Grape Seed Oil Attenuates Myocardial Fibrosis by Inhibiting the PI3K/AKT Signaling Pathway

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Pharmacology

Background:

• Myocardial fibrosis (MF) involves excessive collagen deposition, leading to cardiac dysfunction and cardiovascular diseases.
• Grape seed oil (GSO) has known cardiovascular benefits, but its anti-fibrotic mechanisms require further elucidation.
• Understanding GSO's effects on cardiac fibroblasts (CFs) is crucial for developing novel MF treatments.

Purpose of the Study:

• To investigate the inhibitory effects of GSO bioactive components on transforming growth factor-beta 1 (TGF-β1)-induced fibrosis in CFs.
• To elucidate the molecular mechanisms underlying GSO's anti-fibrotic potential.
• To explore the therapeutic value of grape industry byproducts in cardiovascular medicine.

Main Methods:

• GSO was extracted using supercritical CO2 technology and tested in vitro on TGF-β1-induced CFs.
• Bioactive constituents of GSO were identified using Gas Chromatography-Mass Spectrometry (GC-MS).
• Network pharmacology, molecular docking, and Western blot analysis were employed to predict and validate molecular targets and pathways.

Main Results:

• GSO treatment significantly downregulated TGF-β1-induced fibrotic markers (MMP9, MMP2, Col1a1, TGF, Col I/III, α-SMA) at transcriptional and protein levels.
• GC-MS identified key fatty acids in GSO, including palmitic and linolenic acid.
• GSO inhibited the PI3K-AKT signaling pathway, with molecular docking confirming strong binding of GSO components to core targets like MMP-9 and PTGS2.

Conclusions:

• Fatty acids in GSO, specifically linolenic and palmitic acid, attenuate myocardial fibrosis.
• GSO exerts its anti-fibrotic effects by inhibiting the PI3K/AKT signaling pathway and reducing key fibrotic markers.
• These findings provide a theoretical basis for using GSO in treating myocardial fibrosis and leveraging grape byproducts for cardiovascular health.