Mechanisms Associated with the Effect of Hypericum perforatum and Smilax cordifolia Aqueous Extracts on Hepatic Steatosis in Obese Rats: A Lipidomic Approach

This study aims to evaluate the effect of H. perforatum and S. cordifolia extracts on hepatic steatosis in obese rats, and to elucidate their mechanisms through a lipidomic analysis. Fifty-seven phytochemical compounds are identified in H. perforatum and S. cordifolia aqueous extracts by UPLC-QTOF MSE. Both herbal aqueous extracts ameliorate hepatic steatosis. S. cordifolia modulates arachidonic acid, 16:0-, 16:1-, and 18:0-derived TAG, ceramides, and diacylglycerols, regulating the expression of genes involved in fatty acid (Fas, Acc, and Scd1), diacylglyceride (Gpat) and ceramide (Spt1) biosynthesis, and beta-oxidation (Cpt1 and Acadm). H. perforatum regulates eicosapentanoic acid metabolism, which is associated with Fabp down-regulation. Both extracts reduce hepatic TNF-alpha and IL-6 levels, which is associated with eicosanoid pathway regulation by S. cordifolia and the modulation of phosphatidylcholines and phosphatidylethanolamines by H. perforatum. These results suggest that these aqueous extracts can be used as ingredients for the elaboration of functional beverages with hepatoprotective effects. Practical Applications: This study proposes a lipidomic approach followed by the integration of metabolic networks for the identification of the mechanisms associated with the hepatoprotective effect of herbal extracts. The results obtained in this study demonstrate the beneficial effect of S. cordifolia and H. perforatum aqueous extracts on hepatic steatosis in high-fat and fructose diet-fed obese rats. Therefore, these herbs can be used for the elaboration of functional beverages. H. perforatum and S. cordifolia aqueous extracts ameliorate hepatic steatosis in obese rats. A liver lipidome approach is used to identify the mechanisms associated with their hepatoprotective effect by integrating metabolic networks. H. perforatum decreases Fabp hepatic expression which is associated mainly with decreased hepatic EPA. S. cordifolia decreased Fasn, Acaca, Scd1, Gpat1, and Spt1 and increased Cpt1 and Acadm hepatic expressiobm which is associated mainly with increased AA. These herbs have potential for the development of functional beverages or dietary supplements with hepatoprotective effects.