Systematic Evaluation of the Nutritional Quality, Elemental Safety, and Preventive Effects of Perilla Seed Oil on Hyperlipidemia and Gut Microbiota Dysbiosis in High-Fat Diet-Fed Rats

Background: Perilla seed oil (PSO) is a high-nutritional-value oil and widely used in functional foods, and derives from the mature seeds of Perilla frutescens. This study aimed to systematically evaluate the nutritional characteristics and safety of PSO, as well as to investigate its lipid-modulating effects and the underlying changes in gut microbiota in hyperlipidemic conditions. Methods: The nutritional characteristics of PSO (prepared via seed cleaning, cold-pressing, filtration, and solvent extraction) were evaluated by comparing it with 15 representative vegetable oils, focusing on fatty acid composition, total phenolic and flavonoid contents, metal elements, and physicochemical indices. The safety of PSO was assessed through acute oral toxicity testing in Kunming mice (doses: 2.5, 5, 10 g/kg) with general observations, histopathological examination, and serum biochemical analysis. Additionally, a high-fat diet (HFD)-induced hyperlipidemic Sprague-Dawley (SD) rat model was established to explore PSO’s lipid-modulating effects and its regulatory role in gut microbiota, using serum biochemical detection, liver pathology examination, 16S rRNA gene sequencing, and short-chain fatty acid (SCFA) analysis. Results: PSO possessed the highest α-linolenic acid (ALA) content among the tested oils, along with a favorable unsaturated fatty acid ratio. Notably, PSO was rich in zinc and free of toxic elements. In HFD-fed rats, 10 g/kg PSO significantly reduced serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, increased high-density lipoprotein cholesterol (HDL-C), and alleviated hepatic damage. Moreover, PSO modulated gut microbiota by enriching probiotic populations and elevating intestinal production of short-chain fatty acids (SCFAs), particularly propionate and butyrate. Conclusions: PSO is a nutritionally rich and safe edible oil with notable lipid-modulating properties, highlighting its potential as a dietary intervention for preventing lipid metabolism disorders.