Neolignan Kadsurenin F Modulates Proteostatic Pathways and Possesses Potent Anti‐Inflammatory Properties

Kadsurenin F, a natural neolignan-type compound, has been described as a constituent of various members of the Lauraceae family such as Aniba spp. or Nectandra spp., but can also be found in various Piper species such as Piper kadsura Ohwi (Piperaceae). This species is traditionally used to treat asthma, rheumatic pain, arthritis, and digestive problems. Recently, several studies have highlighted the significant anti-inflammatory potential of P. kadsura extracts and secondary metabolites. Here, we report the isolation of kadsurenin F as an active component of P. kadsura. We found that kadsurenin F increases oxidative load and suppresses proteasome functionality in normal diploid human fibroblasts, and after administration in Drosophila flies. Moreover, kadsurenin F likely possesses anti-inflammatory properties, as apart from suppressing proteasome activity, it reversed inflammatory phenotypes and inhibited NO production in RAW 264.7 macrophage cells when administered in parallel with LPS. Our findings suggest that the kadsurenin F scaffold can be used for the development of novel highly bioactive proteasome inhibitors and/or anti-inflammatory compounds.