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

Five new diterpenes, including four new hydroazulenes, (8,11)-8,11-diacetoxypachydictyol A (), (8*,11*)-6--acetyl-8-acetoxy-11-hydroxypachydictyol A (), (8*,11*)-8-acetoxy-11-hydroxypachydictyol A (), and (8*,11*)-6--acetyl-8,11-dihydroxypachydictyol A (), and a secohydroazulene derivative, named 7-7,8-seco-7,11-didehydro-8- acetoxypachydictyol A (), were isolated from a South China Sea collection of a sp. nov. brown alga, together with five known analogues (-). Structure elucidation was achieved by extensive spectroscopic analysis and comparison with reported data. All compounds showed potent antioxidant effects against HO-induced oxidative damage in neuron-like PC12 cells at a low concentration of 2 μM. The antioxidant property of dictyol C () 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.