(±)-Thymutatusone A, a pair of novel skeleton diterpene from Thymus quinquecostatus and in vitro hepatoprotective activity

A pair of novel skeleton diterpenoid enantiomers, (+)- and (−)-thymutatusone A [(+)- and (−)-1], along with one new and one known biogenetically related compounds (2-3), were isolated from Thymus quinquecostatus. Their structures were exhaustively character-ized by comprehensive spectroscopic data, X-ray diffraction analysis, and ECD (electronic circular dichroism) calculations. Thymuta-tusone A features an unprecedented skeleton with a rare tricyclo [7.3.1.02,7] tridecane motif. The plausible biogenetic pathway of 1 was proposed. Additionally, the hepatoprotective activity of isolates against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells was tested. Compounds (±)-1, (−)-1, and (+)-1 exhibited potent hepatoprotective activity, with EC50 values of 11.5 ± 2.8, 8.4 ± 1.9, and 12.2 ± 0.3 μM, respectively. Further, the western blot analysis showed that compound (−)-1 could increase the expres-sion of PPARα and STAT1 protein and thus exert hepatoprotective activity.