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 structures of the novel compounds were elucidated using comprehensive spectroscopic methods, including electronic circular dichroism (ECD) and nuclear magnetic resonance (NMR) calculations. Compounds 1−32 were assessed for their neuroprotective effects against H₂O₂-induced damage in human neuroblastoma SH-SY5Y cells, as well as their inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. Compound 4 demonstrated the most potent neuroprotective activity against H₂O₂-induced oxidative stress by suppressing G₀/G₁ phase cell cycle arrest, reducing reactive oxygen species (ROS) levels, and inhibiting cell apoptosis through modulation of B-cell lymphoma 2 protein (Bcl-2) and Bcl-2 associated X-protein (Bax) protein expression. Compounds 26, 12, and 28 exhibited PTP1B inhibitory activities with IC₅₀ values ranging from 13.92 to 56.94 μmol·L⁻¹, while compound 12 alone displayed significant inhibitory effects on α-glucosidase with an IC₅₀ value of 43.56 μmol·L⁻¹. Additionally, enzyme kinetic analyses and molecular docking simulations were conducted for compounds 26 and 12 with PTP1B and α-glucosidase, respectively.