Phytochemical Profiling, In Vivo Evaluation, and In Silico Insights Into the Antihyperlipidemic Potential of Thymus...

Hyperlipidemia, a major risk factor for ischemic heart disease, is commonly managed with statins, which, despite their efficacy, are associated with adverse effects such as myopathy. This study evaluated the antihyperlipidemic potential of Thymus linearis extract (250 and 500 mg/kg body weight) in Swiss albino mice (six groups, n = 5) fed a high-cholesterol diet. Biological parameters, including body weight, glycemic indices, lipid profile, biochemical markers, and histopathological changes in the liver and kidney, were assessed. Phytochemical profiling using GC-MS revealed the presence of 12 bioactive compounds. Molecular docking confirmed the strong binding affinities of the metabolites to key targets, including the peroxisome proliferator-activated receptor (PPAR-α), HMG-CoA reductase, and acyl-CoA:cholesterol acyltransferase (ACAT). Density functional theory (DFT) calculations further supported the docking results. MM/GBSA analysis showed that compounds 1, 11, and 12 exhibited binding energies of -73.13, -52.51, and -13.83 kcal/mol, respectively. ADMET studies indicated that, except for compounds 5, 10, and 12, all compounds complied with Lipinski's rule of five. Histological analyses revealed reduced adipocyte and hepatocyte sizes, indicating suppressed adipogenesis and improved hepatic architecture. In conclusion, the extract at 500 mg/kg improved lipid profiles and enhanced insulin sensitivity, comparable to simvastatin (1.5 mg/kg).