## 4 Discussion
Both doses of RCEE (20 mg/kg and 40 mg/kg) led to marked reductions in triglycerides, total cholesterol, LDL-C, and HDL-C levels, suggesting a potential to lower the risk of atherosclerosis and cardiovascular diseases. The hyperlipidemic control group (HCG) exhibited substantial lipid abnormalities, with sharp increases in total cholesterol, LDL, and triglycerides, and decreased HDL, confirming the severity of hyperlipidemia induced by Triton WR-1339. Treatment with RCEE significantly lowered TC, LDL, and TG levels, with the 40 mg/kg dose showing the most pronounced effects. While RCEE also reduced HDL-C levels, this reduction was less significant than other lipid parameters. Fenofibrrate (FF), a standard lipid-lowering drug, similarly reduced TC, LDL, and TG levels, though less effectively than RCEE, particularly at the higher dose. These results affirm that RCEE, particularly at a 40 mg/kg dose, is highly effective in reducing lipid levels, offering a promising natural alternative or complement to conventional treatments like fenofibrrate for managing hyperlipidemia. The significant reductions in harmful lipid levels and the potential cardiovascular benefits underscore the therapeutic potential of _R. chalepensis_ in treating hyperlipidemic conditions. Several notable findings emerge when comparing our study on _R. chalepensis_ to other research. A study on _R. chalepensis_ leaf extract from Tunisia demonstrated significant lipid-lowering effects, with obese rats showing a 44% reduction in serum total cholesterol and a 68% decrease in LDL-C levels. Additionally, the extract led to a remarkable 91% increase in HDL-C levels in rats fed a high-fat, high-fructose diet [21]. These results align with our findings, affirming _R. chalepensis_ as an effective agent for managing hyperlipidemia. However, differences in the extent of lipid modulation between studies may be attributed to variations in experimental models, extract preparation, dosage, and geographical origin of the plant material. In contrast, the study on _R. tuberculata_ revealed mild toxicity at higher doses, with an oral LD50 exceeding 5000 mg/kg. Paracetamol (PCM) administration significantly increased hepatic enzyme activities, cholesterol, triglycerides, and glycemic levels. These adverse effects were substantially reduced by co-treatment with vitamin C and _Ruta_ methanolic extract (RME), with RME showing superior efficacy compared to the aqueous extract (RAE) in preventing PCM-induced histological changes and reducing hepatic damage [22]. Furthermore, _R. chalepensis_ was found to restore zinc levels, improve lipid profiles--by reducing total cholesterol, LDL cholesterol, and triglycerides while increasing HDL cholesterol--and enhance antioxidant defenses in diabetic rats on a zinc-deficient diet [23]. This comprehensive profile underscores the potential therapeutic benefits of different species of _Ruta_ in managing hyperlipidemia and supporting overall health. In Triton WR-1339-induced hyperlipidemia rats, _R. chalepensis_ ethanolic extract (20 mg/kg, 40 mg/kg) reduced lipid levels, which can be attributed to the modulation of several key genes involved in lipid metabolism by modulating multiple essential genes related to cholesterol metabolism, including Peroxisome Proliferator-Activated Receptor Alpha (_Ppara_), Liver X Receptor Alpha (_Lxra_), Sterol Regulatory Element-Binding Protein 1c (_Sreb-1c_), 3-Hydroxy-3-Methylglutaryl-CoA Reductase (_Hmgcr_), and Low-Density Lipoprotein Receptor (_Ldlr_). PPAR-alpha plays a critical role by enhancing the expression of genes like Carnitie Palmitoyl transferase 1A (_Cpt1a_), Acyl-CoA Oxidase 1 (_Acox1_), and lipoprotein lipase (_Lpl_), which are pivotal in promoting fatty acid oxidation and reducing triglyceride levels [24]. Additionally, LXR-alpha upregulates ATP-Binding Cassette Transporter A1 (_Abca1_) and ATP-Binding Cassette Transporter G1 (_Abcg1_), facilitating cholesterol efflux and increasing HDL-C levels while downregulating SREBPP-1c to limit lipid synthesis [25].