Anti‐inflammatory activity of xylopic acid may be attributed to the modulation of Nrf2 and NF‐kB activities

Abstract

For a long time, non‐resolving inflammation has been the bane of our existence [1]. Currently, there are varying treatment and management options for inflammatory conditions. However, the search for newer, alternative management options continues unabated. A key focus of our research is the identification of lead compounds and therapeutically viable compounds from plants. One such compound isolated from Xylopia aethiopica is the kaurene diterpene, xylopic acid (XA). The anti‐inflammatory potential of XA has been established from our previous studies [2, 3]. This current work sets out to identify potential molecular targets of xylopic acid in in vitro and cell‐based assays. The selection of these investigated targets was based on the proven bioactivity of xylopic acid as a potential anti‐inflammatory agent and on predictions from the Spider target prediction webtool. Reporter gene assays were used to test for altered NF‐kB and Nrf2 activities in transfected HEK or CHO cells, respectively. XA at 30 µM significantly (p<0.001) inhibited the NF‐kB‐dependent reporter gene expression (Fig. 1) and enhanced activation of Nrf2 in a concentration‐dependent manner when compared to the control (Fig. 2). Our findings suggest that the anti‐inflammatory mechanism of XA entails the inhibitory effect on NF‐kB and an increased activity of Nrf2.