Alkaloids from <i>Piper longum</i> L and their Anti‐inflammatory Properties

Piper longum L. (PL) is considered one of the most important species traditionally used for treating various ailments and has indicated the presence of alkaloids, flavonoids, and steroids. In this study, we isolated the chemical compounds of PL leaves, and measured NO, IL-6, iNOS, as well as COX-2 protein levels. In addition, molecular docking analysis was used to further understand the anti-inflammation effect of the compounds. We identified one new alkaloid named piperlongumine A (1) with ten known compounds (2-11). The new compound (1) and two other alkaloids 2E)-3-(4-hydroxy-3-methoxyphenyl)-1-(pyrrol-1-yl) propanone (7) and piperchabamide A (8) significantly reduced NO production in LPS-stimulated RAW 264.7 cells with the IC₅₀ values of 0.97±0.05 μM, 0.91±0.07 μM, 1.63±0.14 μM, respectively. Moreover, at concentration of 2 μM, compound 1 inhibited approximately 98±0.64 % of IL-6 secretion, and decreased iNOS and COX-2 protein level by about 96 and 19 folds compared to LPS treatment alone, respectively. Furthermore, compounds 1, 7, and 8 were predicted to bind and inhibit IL-6, TNF-α, and iNOS, with compound 1 showing the highest binding energy of -7.09 kcal/mol. This study provides new insights for potential anti-inflammatory drug design and warrants further investigation.