Acute Toxicity and Antihyperlipidemic Effects of Syringaldehyde with Downregulation of SREBP-2 Gene Expression in Rats

Hyperlipidemia, a condition characterized by elevated lipid levels, presents significant cardiovascular risks. Syringaldehyde (SA), a phenolic aldehyde derived from plants, exhibits antioxidant, antihyperglycemic, and anti-inflammatory properties. However, its potential toxicity and effects on hyperlipidemia have not been studied. In this study, we evaluated the safety profile and antihyperlipidemic effects of SA. To assess acute toxicity, Sprague-Dawley rats were divided into two groups (<i>n</i> = 5 in each group): the control group received a vehicle, while the treatment group was administered a single oral dose of SA 2000 mg/kg, and rats were observed up to 14 days. To investigate the antihyperlipidemic effects of SA, rats were allocated into six groups (<i>n</i> = 5 in each group). Group 1 (control) received a vehicle, group 2 (hyperlipidemic) was treated with tyloxapol (i.p 400 mg/kg), while groups 3-6 received atorvastatin 10 mg/kg and SA 10, 20, and 40 mg/kg, respectively, post tyloxapol injection. The acute toxicity results showed that SA exhibits LD₅₀ above 2000 mg/kg. Hematological analyses showed no significant changes, except for a notable increase in the platelet count. Additionally, SA significantly decreases cholesterol, triglyceride, and creatinine levels, along with elevated alanine transaminase, alkaline phosphatase, and urea levels. Markers of oxidative stress confirmed SA's antioxidant properties, and histopathological examination revealed normal cellular structure of selected organs. In the hyperlipidemic model, SA effectively and dose dependently reduced hyperlipidemia by lowering total cholesterol, triglycerides, and LDL levels and improved hepatocellular structure affected by tyloxapol. Moreover, gene expression analysis demonstrated significant downregulation in SREBP-2 gene expression along with reduced HMG-CoA reductase activity. Overall, this study supports the safety and low toxicity of SA and its promising antihyperlipidemic effects.