Trichodenoids A and B, Two Skeletally Unprecedented Polyketides from Trichoderma reesei with Cardioprotective Effects against H2O2-Induced Injury

Trichoderma reesei, recognized by the FDA as a food-safe strain, plays a vital role in food fermentation. Although the enzymatic applications of T. reesei are well-established, the health benefits of its fermentation-derived metabolites are yet to be fully explored. Trichodenoids A (1) and B (2), two skeletally unprecedented polyketides, were isolated from the endophytic fungus T. reesei originating from the plant Gastrodia elata Blume. Their structures were elucidated via spectroscopic data, single-crystal X-ray crystallographic analysis, quantum chemical DP4+ analysis, and ECD calculation. Compounds 1 and 2 were uniquely defined by the unusual 6/6/5 and 6/6/5/6 ring systems, respectively, which were proposed to be formed through key Diels–Alder and Baeyer–Villiger reactions during biosynthesis. Compound 2 had the potential to mitigate H₂O₂-induced oxidative stress in H9C2 cells by reducing intracellular ROS levels, restoring mitochondrial function, and regulating the mRNA expression related to oxidative stress, inflammation, and autophagy. These findings highlight compound 2 as a potential candidate for natural antioxidants and even as dietary supplements for cardiovascular health.