Discovery of -Clerodane Diterpenoids from as Neuroprotective Agents against Ferroptosis and Neuroinflammation.

Twelve new -clerodane diterpenoids, eight undescribed methoxy/ethoxy acetal analogues, and one new -iridane monoterpenoid were isolated from . Their structures were elucidated using a combination of spectroscopic data, quantum chemical calculations, and X-ray crystallography. This research reveals the distinctive structural features of diterpenes, including distinct C rings and 4,18-double bonds, distinguishing them from diterpenes of other plants in the genus. Compound represents the first example of a 19(5→6)--clerodane formed through a Wagner-Meerwein rearrangement. The isolated compounds were assessed for their neuroprotective effects against RSL3-induced ferroptosis in HT22 cells and LPS-induced neuroinflammation in BV-2 cells. Notably, compound inhibits ferroptosis (EC = 10 μM) with a potentially new mechanism of action. The preliminary structure-activity relationship studies revealed that the furan-clerodane diterpenoids possess potential ferroptosis inhibitory activity, while the lactone-clerodanes do not. This study represents the first report of furan-containing clerodanes within the genus, providing fresh insights into the phytochemistry and pharmacological potential of .