Characteristic Flavaglines with Therapeutic Potential for Ischemic Stroke from <i>Aglaia perviridis</i>

To investigate the material basis and mechanisms underlying the therapeutic effects of <i>Aglaia perviridis</i> on ischemic stroke, the anti-ischemic stroke activities of various crude extracts and derived compounds were evaluated using both middle cerebral artery occlusion/reperfusion (MCAO/R) rat models and lipopolysaccharide (LPS)-induced BV-2 microglia models. The ethyl acetate extract of <i>A. perviridis</i> (APE), which contains total flavaglines, demonstrated the most significant antineuroinflammatory activity in vitro. Furthermore, APE markedly reduced cerebral infarct volume and alleviated cerebral edema in MCAO/R rats. A comprehensive phytochemical analysis of APE led to the isolation and identification of 16 novel compounds (<b>1a</b>, <b>1b</b>, <b>2a</b>, <b>2b</b>, <b>3</b>, <b>4a</b>, <b>4b</b>, <b>5a</b>, <b>5b</b>, <b>6a</b>, <b>6b</b>, <b>7a</b>, <b>7b</b>, <b>8a</b>, <b>8b</b>, and <b>9</b>) and 10 known analogues (<b>10</b>-<b>19</b>). The flavaglines were characterized using high-performance liquid chromatography (HPLC). The structures of the isolated compounds were elucidated through 1D and 2D nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), ACD/Structure Elucidator (ACD/SE) analysis, DP4+ probability analysis, and electronic circular dichroism (ECD) calculations. Notably, compounds <b>1</b> and <b>2</b> were novel valence rearrangement flavanes with a benz[<i>b</i>]furan backbone. Additionally, potential biosynthetic pathways were proposed. In bioassays, compounds <b>5</b> and <b>6</b> potently inhibited LPS-induced nitric oxide (NO) production in BV-2 cells, with IC₅₀ values of 11.21 ± 3.46 and 2.04 ± 1.10 μM, respectively.