Guaiane-type sesquiterpenoids from patchouli oil and their potential anti-depressive effects

Sixteen guaiane-type sesquiterpenoids, including four undescribed 4,5-seco-guaiane derivatives (1-4) and one undescribed guaiane (6), were isolated from the volatile oil of Pogostemon cablin. Their structures were determined using extensive spectroscopic evidence, including NMR, IR, HR-ESI-MS, and ECD calculations. Their anti-depressive effects were evaluated in corticosterone (CORT)-induced PC12 cells in vitro. Compound 5 (7-epi-chabrolidione A) was previously reported by our group to exhibit neuroprotective properties. However, the present study further demonstrated that compounds 1-5 had protective effects against CORT-induced injury in PC12 cells. Hoechst 33258 staining, high-content screening, and western blot analysis revealed that compound 5 activated the CaMKII/CREB/BDNF signaling pathway, thereby reducing apoptosis in CORT-injured PC12 cells and inhibiting intracellular calcium levels. Furthermore, compound 5 effectively rescued reserpine-induced depression and cognitive impairment in zebrafish in vivo. Collectively, these findings indicate that 4,5-seco-guaiane sesquiterpenoids from Pogostemon cablin (especially compound 5) possess potential anti-depressive activity.