Hydroazulene Diterpenes from a Dictyota Brown Alga and Their Antioxidant and Neuroprotective Effects Against Cerebral Ischemia-Reperfusion Injury.

Five new diterpenes, including four new hydroazulenes, (8R,11R)-8,11-diacetoxypachydictyol A (1), (8R*,11R*)-6-O-acetyl-8-acetoxy-11-hydroxypachydictyol A (2), (8R*,11S*)-8-acetoxy-11-hydroxypachydictyol A (3), and (8R*,11S*)-6-O-acetyl-8,11-dihydroxypachydictyol A (4), and a secohydroazulene derivative, named 7Z-7,8-seco-7,11-didehydro-8- acetoxypachydictyol A (5), were isolated from a South China Sea collection of a Dictyota sp. nov. brown alga, together with five known analogues (6-10). Structure elucidation was achieved by extensive spectroscopic analysis and comparison with reported data. All compounds showed potent antioxidant effects against H2O2-induced oxidative damage in neuron-like PC12 cells at a low concentration of 2 μM. The antioxidant property of dictyol C (9) was associated with activation of the Nrf2/ARE signaling pathway; it also showed neuroprotective effects against cerebral ischemia-reperfusion injury (CIRI) in a rat model of transient middle cerebral artery occlusion. As such, hydroazulene diterpenes could serve as lead structures for the development of novel neuroprotective agents against CIRI.