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

Black Pepper (Piper nigrum L.) has been commonly utilized in food preparation as well as traditional medicine in several countries. Seven new amide alkaloids, pipernigramides A-G (3, 10, 38, and 41-44), a new piperic ester, pipernigrester A (48), along with forty-seven known compounds were isolated from the EtOH extract of Piper nigrum. The inhibitory effects on nitric oxide (NO) of all compounds was then evaluated. Among the tested compounds, three of them (42-44) significantly inhibited 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, as well as PGE2 release in RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Moreover, 42-44 suppressed IκB degradation and further inhibited the of p65 subunit cytosol-nucleus translocation by targeting IKK-β. In the carrageenan-induced paw edema test, 42-44 demonstrated anti-inflammatory effects as well. These results indicate that all three compounds from Piper nigrum have the potential anti-inflammatory effects.