Chia Seed Bioactives Ameliorate Diet-Induced Hyperlipidemia and Oxidative Stress: A Dual Mechanism Involving Antioxidant Enhancement and Putative HMG-CoA Reductase Inhibition.

Mitigating oxidative stress and inhibiting HMG-CoA reductase are key pharmacological strategies against hyperlipidemia. This study investigated bioactive fractions from Salvia hispanica L., as a multi-pronged therapeutic agent in a high-fat diet (HFD)-induced hyperlipidemia in rats. Animals received daily oral administration of a chia aqueous extract (CAE), protein isolate (CPI), or protein hydrolysate (CPH) at 400 mg/kg for 12 weeks, with atorvastatin as a positive control. This represents the first systematic comparison of three distinct chia-derived fractions for metabolic intervention. All three fractions significantly improved HFD-induced metabolic derangements. This therapeutic effect was underpinned by a dual mechanism. First, all fractions restored systemic redox homeostasis by reducing lipid peroxidation and bolstering endogenous antioxidant enzymes (SOD, CAT, GPx). Second, the phenolic-rich CAE, containing abundant catechin and quinic acid, exhibited cholesterol-lowering activity. The in silico molecular docking study revealed high-affinity binding of catechin to the catalytic site of HMG-CoA reductase (docking score: -7.616 kcal/mol), suggesting putative enzyme interaction. Our results provide compelling evidence that chia-derived fractions ameliorate hyperlipidemia through both significant antioxidant activity and putative interference with cholesterol biosynthesis, positioning them as a robust nutraceutical strategy for managing metabolic disorders.