Integrated Phytochemical, Molecular Docking, and In Vivo Evidence for the Hypolipidemic Efficacy of Chamomile- and Thyme-Linseed Formulations

Hyperlipidemia is a major global risk factor for cardiovascular disease, underscoring the need for safe, multi-target preventive strategies. In this study, two novel dietary supplements were developed by blending freeze-dried aqueous extracts of chamomile (CDS) or thyme (TDS) with linseed oil (1:1, w/w) and evaluated for their phytochemical composition, antioxidant capacity, and hypolipidemic efficacy. Total phenolics, total flavonoids, fatty acid composition, volatile constituents, and individual phenolic profiles were characterized, while antioxidant activity was assessed using DPPH· radical-scavenging and FRAP assays. Hypolipidemic activity was investigated in a Triton X-100-induced hyperlipidemia rat model through an assessment of plasma lipid parameters, oxidative stress and inflammatory markers, and liver and kidney function indices, supported by hepatic histopathology. Molecular docking was performed to explore the interactions of major bioactive compounds with AMP-activated protein kinase (AMPK) and HMG-CoA reductase. Both CDS and TDS exhibited strong antioxidant activity and high polyphenol content, with kaempferol and chlorogenic acid identified as the predominant phenolics in CDS and TDS, respectively. β-Farnesene and carvacrol were the main volatile constituents. In vivo, both formulations significantly reduced total cholesterol, triglycerides, LDL-C, lipid peroxidation markers, and TNF-α, while increasing HDL-C and improving cardiac risk indices, with more pronounced effects observed for TDS. Histopathological analyses confirmed marked hepatoprotection, particularly in the TDS-treated group. Docking analyses identified ellagic acid as the strongest dual binder to both AMPK and HMG-CoA reductase. Overall, these findings demonstrate that chamomile-linseed and thyme-linseed formulations exert synergistic, multi-target antioxidant and hypolipidemic effects, supporting their potential as nutraceutical strategies for the early prevention and management of hyperlipidemia and cardiometabolic risk.