Abstract

not-yet-known not-yet-known not-yet-known unknown Studies on Ganoderma applanatum yield twelve terpenoids including a rare scaffold of 6/6/5/6 rearranged ganoderic acid and an unprecedented aromatic diterpenoid. The absolute configurations for compounds 1 and 4 were ascertained using X-ray and DTF calculations, respectively. Among all compounds, ganorcleiol ( 4) and applanoic acid C ( 6) demonstrated significant neuroprotective activity in inhibiting glutamate-induced HT22 cell death. Biochemical assays suggest that applanoic acid C may exert protective effects by activating the Nrf2/HO-1 pathway, whereas ganorcleiol does not appear to be associated with this pathway. Surface Plasmon Resonance (SPR) analysis were used to predict its potential target proteins. A set of 49 targets was identified from over 20,000 proteins in HT22 cell. These findings indicated that ganorcleiol may mitigate neuronal damage by reducing glutamate absorption and transport through the regulation of the SLC family of transporters. Additionally, it has been involved in the modulation of oxidative stress, apoptosis, via the AKT pathway. In the following Western blot (WB) experiments, it was further verified that ganorcleiol can exert neuroprotective effects through the PI3K-AKT-mTOR pathway. These outcomes offer valuable insights for the study of action of trace bioactive components from edible materials and contribute to the broader understanding of neuroprotective compounds.