Effects of Cynara scolymus L. Bract Extract on Lipid Metabolism Disorders Through Modulation of HMG-CoA Reductase, Apo A-1, PCSK-9, p-AMPK, SREBP-2, and CYP2E1 Expression

<b>Background/Objectives:</b> Hyperlipidemia is a major contributor to metabolic complications and tissue damage, leading to conditions such as liver steatosis, atherosclerosis, and obesity. This study aimed to investigate the effects of aqueous artichoke bract extract (AE) on lipid metabolism, liver antioxidative defense, and liver steatosis in mice fed a high-fat, high-sucrose diet while elucidating the underlying mechanisms. <b>Methods:</b> An 8-week study used hyperlipidemic mice treated with AE at daily doses of 100 and 200 mg/kg bw, compared to fenofibrate. Plasma, liver, fecal, and biliary lipids, as well as blood glucose, were analyzed enzymatically. The liver antioxidative defense was assessed by measuring reduced glutathione, malondialdehyde (MDA), and antioxidant enzyme activities, while liver steatosis was evaluated through transaminase and alkaline phosphatase activities and histological monitoring of lipid droplets. Polyphenol profiling and quantification were performed using HPLC-DAD, and potential mechanisms were predicted by molecular docking and confirmed in HepG2 cells. <b>Results:</b> At 200 mg/kg, AE significantly improved plasma lipid profiles by reducing total cholesterol, triglycerides, and LDL-cholesterol while increasing HDL-cholesterol. It facilitated cholesterol reduction in the liver and its excretion, indicating activation of reverse cholesterol transport, which led to reduced body weight and liver steatosis. AE lowered MDA levels and enhanced antioxidant enzyme activities. AE was found to be safe (LD50 > 5000 mg/kg) and modulated gene expression in HepG2 cells. <b>Conclusions:</b> Based on our results, the artichoke bract extract could be considered a natural resource of bioactive compounds to treat hyperlipidemia and related cardiometabolic diseases.