Reynoutrin Mitigates Metabolic, Immune, and Redox Dysregulation in Acute Dyslipidemia

Acute dyslipidemia is a key contributor to metabolic disturbances, often driven by lipid imbalance, and systemic inflammation.This study explored the potential of reynoutrin, a bioactive flavonoid glycoside, in counteracting lipid abnormalities and their associated oxidative and inflammatory responses in a rat model of acute dyslipidemia.Reynoutrin (25 and 50 mg/kg) was administered orally for 14 days, followed by the induction of acute dyslipidemia using poloxamer-407 (P407).Biochemical analyses included lipid profile assessment, hepatic lipid-regulating enzyme activity, oxidative stress biomarkers, and inflammatory mediators.The HMG-CoA reductase and fatty acid synthase (FAS) inhibitory activities of reynoutrin were determined.P407 administration resulted in marked elevations in plasma cholesterol, triglycerides, vLDL-C, and LDL-C, with reductions in HDL-C and lipoprotein lipase activity.Reynoutrin treatment mitigated these effects, normalized lipid parameters, and downregulated hepatic HMG-CoA reductase and FAS.It also enhanced LDL-R expression.Reynoutrin significantly reduced hepatic malondialdehyde and nitric oxide while boosting antioxidant enzyme levels.Inflammatory cytokines and NF-κB p65 expression were elevated in dyslipidemic rats but significantly attenuated following reynoutrin administration.Reynoutrin exhibited binding affinities with HMG-CoA reductase, LDL-R PCSK9 binding domain, and FAS KS and TE domains.In conclusion, reynoutrin exhibits potent lipid-lowering, antioxidant, and anti-inflammatory properties, potentially via modulation of lipid metabolism, redox balance, and immune signaling in acute dyslipidemia.These findings suggest its therapeutic promise in managing dyslipidemia-associated complications.