High levels of fats like triglycerides and cholesterol in the blood can cause cardiovascular diseases, prompting the search for safer, natural treatments. This study investigates the efficacy of Ruta chalepensis ethanol extract in lowering cholesterol levels using a rat model of hyperlipidemia induced by Triton WR-1339. Leaves and flowers of R. chalepensis were extracted with ethanol, and LC-MS analysis revealed high levels of quercetin (9.5%), 2,2-Dimethyl-3-methylidenebicyclo [2.2.1] heptane (8.1%), and other compounds, with monoterpenes being the most common class. Male Wistar rats received doses of the extract at 20 and 40 mg/kg, while fenofibrate (100 mg/kg) was the positive control. After 20 h, plasma lipid levels were significantly affected, showing a 72.1% reduction in total cholesterol for the 40 mg/kg group (p < 0.01) and a 67.6% reduction for the 20 mg/kg group (p < 0.01). High-density lipoprotein cholesterol levels decreased by 68.8% in the 40 mg/kg group (p < 0.01) and 58.6% in the 20 mg/kg group (p < 0.01). Low-density lipoprotein cholesterol saw reductions of 67.3% (p < 0.001) in the 40 mg/kg group and 60.4% (p < 0.01) in the 20 mg/kg group. Triglycerides dropped by 90.6% in the 40 mg/kg group (p < 0.001) and 86.7% in the 20 mg/kg group (p < 0.001). Overall, the results highlighted a stronger anti-hyperlipidemic effect in the 40 mg/kg group across all lipid parameters measured. The extract outperformed fenofibrate, particularly at the higher dose. These results imply that R. chalepensis extract is a promising natural alternative for managing hyperlipidemia.

Achillea santolina is traditionally utilized in herbal therapy; nonetheless, its xanthine oxidase inhibitory and cellular antioxidant properties are not extensively investigated. This work aimed to identify the phytochemical composition of the methanolic extract of A. santolina aerial parts via LC–MS and to assess its xanthine oxidase (XO) inhibitory activity and its modulatory effects on intracellular reactive oxygen species (ROS) in HepG2 cells. The methanolic extract underwent LC–MS analysis for phytochemical identification, and XO inhibitory activity was assessed spectrophotometrically using allopurinol as the reference medication. Intracellular ROS levels were determined using the DCFH-DA fluorescent assay following xanthine-induced oxidative stress. LC–MS profiling identified ten compounds representing 95.1% of the extract, with flavonoid glycosides (44.1%) as the predominant class. Rutin (18.6%) and luteolin-7-O-glucoside (15.2%) were the major constituents. The extract demonstrated concentration-dependent inhibition of XO, with an IC₅₀ value of 29.3 ± 0.4 µg/mL, compared to 2.1 ± 0.3 µg/mL for allopurinol. In HepG2 cells, xanthine significantly increased ROS production, while pre-treatment with the extract greatly diminished ROS levels in a dose-dependent manner, reaching approximately 75% inhibition at 50 µg/mL. The results demonstrate that the methanolic extract of A. santolina exhibits significant xanthine oxidase inhibitory and antioxidant properties, possibly due to its elevated flavonoid concentration, indicating its potential utility in addressing oxidative stress-related disorders. To the best of our knowledge, this study provides the first report on the combined xanthine oxidase inhibitory and intracellular ROS-modulating activities of A. santolina methanolic extract.