AUTHOR=El Rabey Haddad A. , Attia Eman S. , Bakry Nadia , Rezk Samar M. , Sharfeldin Asmaa Y. TITLE=Comparison between the protective effect of the orally administered atorvastatin and safflower (Carthamus tinctorius) in hypercholesterolemic male rats JOURNAL=Frontiers in Pharmacology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1663717 DOI=10.3389/fphar.2025.1663717 ISSN=1663-9812 ABSTRACT=Hyperlipidemia is correlated with the elevation of cholesterol and triglyceride levels in the blood that increase the risk of cardiovascular events, such as heart attacks and strokes. This study aimed to test the hypolipidemic activity and other health benefits of atorvastatin and safflower (Carthamus tinctorius L., family Asteraceae) on rats with induced hypercholesterolemia in a four-week study. 24 male albino rats were divided into four groups (n = 6). The first group (G1) was given a normal basal diet as a negative control, while the other rats received a high-fat diet with 5% cholesterol. The second group (G2) served as the positive control, receiving no treatment. The third group (G3) received 200 mg/kg body weight safflower aqueous extract, and the 4th group (G4) received 20 mg/kg body weight atorvastatin. The induced hypercholesterolemia significantly raised liver function enzymes, lipid peroxidation (14.9 ± 0.11 mg/dL), total cholesterol (273.3 ± 1.1 mg/dL), triglycerides (223.0 ± 4.1 mg/dL), low-density lipoproteins (204.7 ± 0.9 mg/dL), very low-density lipoproteins (44.6 ± 0.8 mg/dL), troponin, creatine kinase (CK), and adrenaline while decreased antioxidant enzymes, high-density lipoprotein (HDL), and vitamin D (11.1 ± 0.5 ng/mL). The liver and heart tissues were also significantly injured by hypercholesterolemia. Administration of atorvastatin and safflower markedly ameliorated the biochemical and histological abnormalities associated with induced hyperlipidemia, restoring them to near-normal levels. Atorvastatin treatment in G4 demonstrated superior efficacy compared to safflower extract in addressing hypercholesterolemia, despite the latter’s significant hypolipidemic effect observed in G3.