Neuroprotective and antidiabetic lanostane-type triterpenoids from the fruiting bodies of Ganoderma theaecolum

Eight previously undescribed lanostane triterpenoids, including five nortriterpenoids with 26 carbons, ganothenoids A−E (1−5), and three lanostanoids, ganothenoids F−H (6−8), along with 24 known ones (9−32), were isolated from the fruiting bodies of Ganodrma theaecolum. The chemical structures of new compounds were determined by extensive spectroscopic methods, as well as electronic circular dichroism (ECD) and NMR calculations. Compounds 1−32 were evaluated for their neuroprotective effects against H₂O₂-induced damage in human neuroblastoma SH-SY5Y cells, as well as protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities. Among them, compound 4 exhibited the most significant neuroprotective activity against H₂O₂-induced oxidative stress by depressing stagnation in the G0/G1 phase of cell cycle, attenuating reactive oxygen species (ROS) level and suppressing cell apoptosis via regulating the protein expression levels of Bcl-2 and Bax. Compounds 26, 12, and 28 displayed PTP1B inhibitory activities with IC₅₀ values ranging from 13.92 to 56.94 μM, while only compound 12 exhibited potent inhibitory effect on α-glucosidase with IC₅₀ value of 43.56 μM. The enzyme kinetic analysis and molecular docking simulations for compounds 26 and 12 with PTP1B and α-glucosidase, respectively, were also performed.