Six new 8-O-4'-linked sesquineolignans from the stems of Kadsura longipedunculata and their neuroprotective effects against 6-OHDA-induced injury in PC12 cells.

Six previously undescribed sesquineolignans, longipedunlignans A-F (1-6), were isolated from the stems of Kadsura longipedunculata. Their structures were elucidated by extensive spectroscopic analysis, including HRESIMS and 1D and 2D NMR data. Compounds 1-6 possess closely related sesquineolignan frameworks composed of three C6-C3 phenylpropanoid units connected through two consecutive 8-O-4' ether linkages. All isolates were evaluated for neuroprotective effects against 6-OHDA-induced injury in PC12 cells. Compounds 3 and 4 exhibited the most pronounced protective effects and attenuated oxidative stress by suppressing ROS accumulation and restoring SOD activity. These findings expand the structural diversity of Kadsura lignans and highlight a rare series of 8-O-4'-linked sesquineolignans from Kadsura as neuroprotective natural product scaffolds worthy of further investigation.