Xylopia aethiopica and Phyllanthus muellerianus are medicinal plants which are widely used in folkloric medicine for the management of various conditions including inflammation, pain, wounds and infections in West Africa [1, 2]. The aim of the project was to identify potential molecular targets of xylopic acid (isolated from Xylopia aethiopica), the ellagitannin geraniin (isolated from Phyllanthus muellerianus) and its gut metabolites, ellagic acid and urolithin A in in vitro and cell-based assays. Reporter gene assays in CHO and HEK 293 cell lines were employed to determine the influence of xylopic acid, geraniin and its gut metabolites on the activation of Nrf2, FXR, RXR, LXR, PPARγ, TGR5and on the inhibition of NF-kB signaling. Test compounds were subjected to proliferation and migration assays in vascular smooth muscle cells (VSMC) and tested for their influence on vascular adhesion molecule (VCAM) and heme oxygenase (HO)-1 expression.
At 30 µM xylopic acid moderately reduced VCAM expression and showed inhibition of NFkB- and activation of Nrf2 signaling. Geraniin (30 μM) and urolithin A (10 μM) increased the expression of HO1 protein levels in VSMC. Geraniin and ellagic acid at 30 μM exhibited anti-migratory activity in VSMC. Additionally, 30 μM urolithin A inhibited VSMC proliferation. Xylopic acid, geraniin and ellagic acid did not positively influence LXR, RXR, PPAR, FXR and TGR5 in reporter gene assays. Urolithin A was able to very weakly induce a RXR-dependent luciferase signal. Xylopic acid could be shown to possess a moderate anti-inflammatory activity as evident in reduced VCAM expression which is possibly due to activation of Nrf2 and inhibition of NFkB. Geraniin and/or its gut metabolites could be shown to significantly increase the expression of HO-1 protein levels in vascular smooth muscle cells and to interfere with VSMC migration and proliferation.
References
[1]Woode et al., (2012). J Pharm BioAll Sci 4(4): 291-301.
[2]Agyare et al., (2009). J. Ethnopharmacol, 125(3): 393-403.