Anti-inflammatory Flavonoid C-Glycosides from Piper aduncum Leaves

Abstract

Four new compounds, acacetin 8-C-[<i>β</i>-D-apiofuranosyl-(1 → 2)-<i>β</i>-D-glucopyranoside] (<b>1</b>), 7-methoxyacacetin 8-C-[<i>β</i>-D-apiofuranosyl-(1 → 3)-<i>β</i>-D-glucopyranoside] (<b>2</b>), 7-methoxyacacetin 8-C-[<i>β</i>-D-glucopyranosyl-(1 → 2)-<i>β</i>-D-glucopyranoside] (<b>3</b>), and 4‴-O-acetylacacetin 8-C-[<i>α</i>-L-rhamnopyranosyl-(1 → 2)-<i>β</i>-D-glucopyranoside] (<b>4</b>), along with ten known compounds (<b>5</b>-<b>14</b>), were isolated from <i>Piper aduncum</i> leaves. The effects of these compounds on lipopolysaccharide-induced expression of the proinflammatory cytokines IL-12 p40, IL-6, and TNF-<i>α</i> in bone marrow-derived dendritic cells were evaluated. Compounds <b>2, 3, 6, 8, 9</b>, and <b>11</b>-<b>13</b> inhibited the production of both IL-12 p40 and IL-6, with IC₅₀ values ranging from 0.35 ± 0.01 to 1.40 ± 0.04 µM and 1.22 ± 0.02 to 3.79 ± 0.10 µM, respectively. Compounds <b>5</b> and <b>10</b> only showed strong inhibition effects on the production of IL-12 p40, with IC₅₀ values of 2.76 ± 0.08 and 0.39 ± 0.05 µM, respectively. However, all compounds showed weak activity or no activity on TNF-<i>α</i> production at the tested concentrations.