Alkaloids from Black Pepper (<i>Piper nigrum</i> L.) Exhibit Anti-Inflammatory Activity in Murine Macrophages by Inhibiting Activation of NF-κB Pathway

Abstract

Black pepper (<i>Piper nigrum</i> L.) has been commonly utilized in food preparation and traditional medicine in several countries. Seven new amide alkaloids, pipernigramides A-G (<b>3</b>, <b>10</b>, <b>38</b>, and <b>41</b>-<b>44</b>), a new piperic ester, pipernigrester A (<b>48</b>), along with 47 known compounds were isolated from the EtOH extract of <i>P. nigrum</i>. The inhibitory effects on nitric oxide (NO) of all compounds were then evaluated. Among the tested compounds, three of them (<b>42</b>-<b>44</b>) significantly inhibited inducible nitric oxide synthase (iNOS)-mediated NO (IC₅₀ = 4.74 ± 0.18, 4.08 ± 0.19, and 3.71 ± 0.32 μM, respectively), and IL-1β, IL-6, TNF-α, and PGE₂ release in RAW 264.7 cells stimulated by lipopolysaccharide. Moreover, <b>42</b>-<b>44</b> suppressed IκB degradation and further inhibited the cytosol-nucleus translocation of the p65 subunit by targeting IKK-β. In the carrageenan-induced paw edema test, <b>42</b>-<b>44</b> demonstrated anti-inflammatory effects as well. These results indicate that all three compounds from <i>P.nigrum</i> have the potential anti-inflammatory effects.