Alkaloids from Black Pepper ( L.) Exhibit Anti-Inflammatory Activity in Murine Macrophages by Inhibiting Activation of NF-κB Pathway.

Black pepper ( L.) has been commonly utilized in food preparation and traditional medicine in several countries. Seven new amide alkaloids, pipernigramides A-G (, , , and -), a new piperic ester, pipernigrester A (), along with 47 known compounds were isolated from the EtOH extract of . The inhibitory effects on nitric oxide (NO) of all compounds were then evaluated. Among the tested compounds, three of them (-) significantly inhibited inducible nitric oxide synthase (iNOS)-mediated NO (IC = 4.74 ± 0.18, 4.08 ± 0.19, and 3.71 ± 0.32 μM, respectively), and IL-1β, IL-6, TNF-α, and PGE release in RAW 264.7 cells stimulated by lipopolysaccharide. Moreover, - 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, - demonstrated anti-inflammatory effects as well. These results indicate that all three compounds from have the potential anti-inflammatory effects.