Antioxidant and Neuroprotective Xenicane Diterpenes from the Brown Alga Dictyota coriacea .

Five new xenicane diterpenes, including three rare nitrogen-containing derivatives, dictyolactams A ( 1 ) and B ( 2 ) and 9-demethoxy-9-ethoxyjoalin ( 3 ), a rare diterpene with a cyclobutanone moiety, named 4-hydroxyisoacetylcoriacenone ( 4 ), and 19- O -acetyldictyodiol ( 5 ), were isolated from an East China Sea collection of the brown alga Dictyota coriacea , along with 15 known analogues ( 6 - 20 ). The structures of the new diterpenes were elucidated by spectroscopic analyses and theoretical ECD calculations. All compounds had cytoprotective effects against oxidative stress in neuron-like PC12 cells. The antioxidant mechanism of 18-acetoxy-6,7-epoxy-4-hydroxydictyo-19-al ( 6 ) was related to the activation of Nrf2/ARE signaling pathway; it also showed significant neuroprotective effects against cerebral ischemia-reperfusion injury (CIRI) in vivo . This study provided xenicane diterpene as a promising lead scaffold for the development of potent neuroprotective agents against CIRI.