Ganoapplins A and B with an unprecedented 6/6/6/5/6-fused pentacyclic skeleton from Ganoderma inhibit Tau pathology through activating autophagy

Ganoapplins A and B (1 and 2) with a 6/6/6/5/6-fused pentacyclic skeleton containing an aromatic E ring, were obtained from Ganoderma applanatum. Their structures were established through extensive spectroscopic ana -lyses, quantum chemical calculations, including calculated chemical shifts with DP4 + analysis and electronic circular dichroism (ECD). A plausible biosynthetic pathway for 1 and 2 was proposed. Furthermore, their roles in activating autophagy were investigated and the cellular assays showed that 1 and 2 can inhibit tau pathology by inducing autophagy, suggesting their potential against Alzheimer's disease (AD).

Automated summary

Ganoapplins A and B (1 and 2) with a 6/6/6/5/6-fused pentacyclic skeleton containing an aromatic E ring were isolated from Ganoderma applanatum. Their structures were determined through spectroscopic analyses, quantum chemical calculations, and the study of their roles in autophagy activation. Cellular assays demonstrated that 1 and 2 can inhibit tau pathology by inducing autophagy, indicating their potential as a treatment for Alzheimer's disease (AD).