Background: Hypercholesterolemia and oxidative stress consider the main causes for atherosclerotic cardiovascular diseases, that are one of the major non-communicable diseases responsible for more than a third of deaths in Saudi Arabia. Cholesterol-lowering medications as Atorvastatin® (ATOR) are linked to a variety of side effects. Achillea fragarntissima (AF) is a valuable medicinal plant in Saudi Arabia with potent antioxidant activity.

Aim: The current study was performed to determine the efficacy of AF in the treatment of hypercholesterolemia through the antioxidant metabolic pathway.

Methodology: Dried aerial parts of AF were extracted by ethanol (70%). Induction of hypercholesterolemia in rats was induced through feeding a high fat-cholesterol diet (HFCD) for 8 weeks. Rats were assigned to two main groups; control group (Cont, n=10) rats fed a standard diet, and hypercholesterolemic group (HFCD) (n=40) rats fed HFCD. The HFCD group was further assigned after measured lipid profile to confirm the induction of hypercholesterolemia to HFCD; HFCD+AF (hypercholesterolemic rats treated orally with 500 mg/kg AF); HFCD+ ATOR (hypercholesterolemic rats treated orally with 20 mg/kg ATOR, as a reference drug); and HFCD+AF+ATOR (hypercholesterolemic rats treated orally with AF+ ATOR). Different treatments were ingested to rats for 4 weeks.

Results: The results revealed that the HFCD group showed significant hyperlipidemia (elevation of serum TC, TG, LDL-C, and VLDL-C levels concurrent with a reduction in serum HDL-C level); significant disturbance in liver functions (elevation in serum ALT, AST, and ALP enzymes activities); and significant oxidative stress (elevation in hepatic MDA level with a reduction in hepatic SOD activity) compared with the Cont group. Besides, hepatic central vein section showed deposition of large lipid within hepatocytes and abundant focal cell necrosis. Oral treatment with AF, ATOR, and the mixture of the drug and AF produced significant hypocholesterolemia, antioxidant, and improved liver function enzymes, with normalized hepatic central vein tissue compared with the HFCD group. The mixture of AF+ATOR had a superior effect than either treatment alone.

Conclusion: In hypercholesterolemic rats, AF may be used to prevent atherosclerosis through improving lipid profile levels, protecting against hepatic oxidative stress, and ameliorating hepatic functions. Thus highlighting its valuable effects in the treatment of atherosclerotic cardiovascular diseases.