Antioxidant and Neuroprotective Xenicane Diterpenes from the Brown Alga Dictyota coriacea

[Image: see text] 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.