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 cyclo-butanone 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.