Hydroazulene Diterpenes from a <i>Dictyota</i> Brown Alga and Their Antioxidant and Neuroprotective Effects Against Cerebral Ischemia-Reperfusion Injury

Abstract

Five new diterpenes, including four new hydroazulenes, (8<i>R</i>,11<i>R</i>)-8,11-diacetoxypachydictyol A (<b>1</b>), (8<i>R</i>*,11<i>R</i>*)-6-<i>O</i>-acetyl-8-acetoxy-11-hydroxypachydictyol A (<b>2</b>), (8<i>R</i>*,11<i>S</i>*)-8-acetoxy-11-hydroxypachydictyol A (<b>3</b>), and (8<i>R</i>*,11<i>S</i>*)-6-<i>O</i>-acetyl-8,11-dihydroxypachydictyol A (<b>4</b>), and a secohydroazulene derivative, named 7<i>Z</i>-7,8-seco-7,11-didehydro-8- acetoxypachydictyol A (<b>5</b>), were isolated from a South China Sea collection of a <i>Dictyota</i> sp. nov. brown alga, together with five known analogues (<b>6</b>-<b>10</b>). 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 (<b>9</b>) 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.