| Summary: | A chemical study of <i>Aesculus wilsonii</i> Rehd. (also called Suo Luo Zi) and the in vitro anti-inflammatory effects of the obtained compounds was conducted. Retrieving results through SciFinder showed that there were four unreported compounds, aeswilosides I–IV (<b>1</b>–<b>4</b>), along with fourteen known isolates (<b>5</b>–<b>18</b>). Their structures were elucidated by extensive spectroscopic methods such as UV, IR, NMR, [α]<sub>D</sub>, and MS spectra, as well as acid hydrolysis. Among the known ones, compounds <b>5</b>, <b>6</b>, <b>8</b>–<b>10</b>, and <b>12</b>–<b>16</b> were obtained from the <i>Aesculus</i> genus for the first time; compounds <b>7</b>, <b>11</b>, <b>17</b>, and <b>18</b> were first identified from this plant. The NMR data of <b>5</b> and <b>18</b> were reported first. The effects of <b>1</b>–<b>18</b> on the release of nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW264.7 cells were determined. The results showed that at concentrations of 10, 25, and 50 μM, the novel compounds, aeswilosides I (<b>1</b>) and IV (<b>4</b>), along with the known ones, 1-(2-methylbutyryl)phloroglucinyl-glucopyranoside (<b>10</b>) and pisuminic acid (<b>15</b>), displayed significant inhibitory effects on NO production in a concentration-dependent manner. It is worth mentioning that compound <b>10</b> showed the best NO inhibitory effect with a relative NO production of 88.1%, which was close to that of the positive drug dexamethasone. The Elisa experiment suggested that compounds <b>1</b>, <b>4</b>, <b>10</b>, and <b>15</b> suppressed the release of TNF-α and IL-1β as well. In conclusion, this study enriches the spectra of compounds with potential anti-inflammatory effects in <i>A. wilsonii</i> and provides new references for the discovery of anti-inflammatory lead compounds, but further mechanistic research is still needed.
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