<p>Our primary focus in this research was to identify and characterize its bioactive compounds for potential therapeutic use. Twenty-seven metabolites of <i>Polygonum orientale</i> were identified using LC-QTOF tandem mass spectrometry. Interestingly, <i>P. orientale</i> extracts included several highly oxygenated flavonoids were isolated from <i>P. orientale</i> by column chromatography. <sup>13</sup>C NMR data of highly oxygenated flavonoids (<b>1–7</b>) are reported here for the first time. In addition, nitric oxide, 1,1-diphenyl-2-picrylhydrazyl, and water-soluble tetrazolium salt assays were carried out on the isolated compounds to investigate their anti-inflammatory, anti-oxidant, and neuroprotective activities, respectively. Compounds <b>1</b>, <b>2</b>, <b>3</b>, <b>5</b>, <b>7</b>, and <b>8</b> significantly attenuated lipopolysaccharide-stimulated NO production in BV2 cells without affecting cell viability. Compounds <b>9–12</b> exhibited significant antioxidant activity, while compounds <b>8</b>, <b>9,</b> and <b>12</b> exhibited protective effects against glutamate-induced neurotoxicity in HT22 cells. Our results indicate that <i>P. orientale</i> is a promising source of natural agents for the potential treatment of inflammation and neurodegenerative diseases.</p> <p>Chemical profile of <i>Polygonum orientale</i>.</p
