Metabolic profiling of bioactive components from Schizophyllum commune Fries in hypercholesterolemic Wistar-Kyoto rats using LC-QTOF-MS analysis

Atherosclerosis is an inflammatory condition that contributes to myocardial infarction, cardiac arrest and stroke. Current knowledge of mushroom metabolomics in the context of atherosclerosis remains inadequate. Hence, further investigation into the underlying pathways and characterization of metabolites is necessary to establish a significant network for early-stage diagnosis of atherosclerosis. Therefore, the standard phytopreparation of Schizophyllum commune (SPPSC) was administered in hypercholesterolemic-induced rats. Sera were evaluated for lipid profile parameters; hepatic marker enzymes and the metabolic profile characterization was determined via liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). SPPSC suppressed the elevation of cholesterol, LDL, triglyceride and atherogenic coefficient levels while increased HDL concentration and restored the function of hepatic antioxidant enzymes. The predictive accuracies and partial least square discriminant analysis (PLS-DA) revealed clear separation in metabolic features between normal, untreated, olive oil and SPPSC treated groups. Pathway analysis of the most significant metabolites targeted towards anti-atherosclerotic and cardio-protective activities were tryptophan metabolism, sphingolipid metabolism, β-alanine metabolism, taurine and hypotaurine metabolism, glutathione metabolism, phenylalanine metabolism, primary bile acid biosynthesis, histidine metabolism, pantothenate and CoA biosynthesis and cysteine and methionine metabolism. Identified metabolites indicate that S. commune is novel in preventing atherosclerosis and enhancing endogenous antioxidant system, protecting the cardiovascular system, minimalizing inflammation and regulating endothelial dysfunction.