###### Abstract  
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 monoter genes being the most common class. Male Wistar rats received doses of the extract at 20 and 40 mg/kg, while fenofibrrate (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 fenofibrrate, particularly at the higher dose. These results imply that _R. chalepensis_ extract is a promising natural alternative for managing hyperlipidemia. Ruta chalepensis; anti-hyperlipidemic activity; hyperlipidemia; Triton WR-1339; lipid profiles; LC-MS +
Footnote †: journal:  
_Ruta chalepensis_, commonly known as fringed rue, is a perennial herb traditionally used in various cultures for its medicinal properties [9]. This plant is rich in bioactive compounds, including flavonoids, alkaloids, coumarins, and essential oils, contributing to its diverse biological activities, such as antioxidant [10; 11], cytotoxic [12], antihemolytic [12], and antibacterial activity [10; 11]. Among these, its potential anti-hyperlipidemic effect has recently gained significant attention, sparking intrigue and interest in the research community. Animal models of induced hyperlipidemia are commonly employed to assess the lipid-lowering potential of natural products, as they effectively mimic human hyperlipidemic conditions. This study utilized a rat model of Triton WR-1339-induced hyperlipidemia to evaluate the anti-hyperlipidemic effects of _Ruta chalepensis_ ethanolic extracts. The model simulates the pathological elevation of plasma lipid levels observed in humans [13] providing a controlled environment for systematically investigating the extract's impact on lipid metabolism and cardiovascular health. The extract's efficacy was comprehensively evaluated by measuring key indicators such as blood total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) markers, offering insights into its potential for improving lipid profiles and overall cardiovascular health. Besides pharmacological induction, dietary methods like the atherogenic diet in Wistar rats are commonly employed to mimic hyperlipidemic circumstances. These models offer insights into long-term lipid metabolism, liver histology, and cardiovascular health by feeding rats high-cholesterol or high-fat diets over extended periods. The model of atherogenic diet, as presented by [PERSON] et al. [14], is a proper adjunctive technique in the study of hyperlipidemia since it has been demonstrated to cause pathological alterations such as thickening of the abdominal aorta and hyperlipidemia. Based on the particular goals of the study, either of the two models can be chosen because they each have unique benefits. Investigating the anti-hyperlipidemic potential of _R.