Whole-grain millets attenuate atherosclerosis by modulating cholesterol metabolism and the FGF-2/PI3K/Akt and Wnt-1/β-catenin pathways in high-cholesterol-fed rats

Cell Mol Biol (Noisy-le-grand). 2025 Dec 28;71(12):22-30. doi: 10.14715/cmb/2025.71.12.4.

ABSTRACT

Millets, rich in nutrients, have the potential to enhance immunity and combat diseases, including atherosclerosis. As a chronic inflammatory disease contributing to high global mortality, atherosclerosis involves key signaling pathways such as Reverse Cholesterol Transport, FGF-2, and Wnt-1/β-catenin. Hence, this study investigated the anti-atherogenic effects of wholegrain millets on these pathways in high-cholesterol-fed rats, highlighting their potential as plant-based therapeutic alternatives to current treatments with adverse effects. Serum lipid profile, atherogenic index, tissue cholesterol levels, activity of lipogenic enzymes, hepatic 3-hydroxy-3-methylglutaryl-CoA reductase, plasma lecithin cholesterol acyl transferase, cardiac and inflammatory markers, gene expression of key lipid metabolism and FGF-2-Wnt-1 pathway genes by RT PCR and qPCR. Protein levels of the FGF-2-Wnt-1 pathway by ELISA and histopathological and Oil-red-O analysis were evaluated. 10% millet intervention significantly improved lipid metabolism by normalizing lipid profiles, reducing atherogenic index, lowering tissue cholesterol and lipogenic enzyme activities, enhancing LCAT activity, upregulating ABCA1 and Apo A1, and downregulating Apo B in HCD-fed rats. Among the millets, Little Millet (LM) showed the most potent effect, significantly reducing cardiac markers (CK-MB, LDH, CRP), downregulating FGF-2/PI3K/Akt and Wnt-1/β-catenin signaling by upregulating GSK3β, and improving aortic structure with no lipid accumulation as shown by Oil-red O staining. Our study suggests that whole-grain millet consumption can effectively reduce atherosclerosis progression. Specifically, LM shows strong potential as a natural intervention for managing atherosclerosis through its regulatory effects on key signaling pathways.

PMID:41456266 | DOI:10.14715/cmb/2025.71.12.4