Reverse Pharmacognosy: Application of Selnergy, a New Tool for Lead Discovery. The Example of ε-Viniferin

Quoc-Tuan      Do; Isabelle      Renimel; Patrice      Andre; Claire      Lugnier; Christian   D.   Muller; Philippe      Bernard

doi:10.2174/1570163054866873

Abstract

The aim of reverse pharmacognosy is to find new biological targets for natural compounds by virtual or real screening and identify natural resources that contain the active molecules. To demonstrate the applicability of this concept, we report here a study on εviniferin, an active ingredient for cosmetic development. Nevertheless, this natural substance is weakly defined in terms of biological properties. SELNERGY, an inverse docking computer software, was used to identify putative binding biological targets for εviniferin. Among the 400 screened proteins two targets were retained. For cosmetic application, cyclic nucleotide phosphodiesterase 4 (PDE4) was the most interesting candidate. Moreover, other PDE subtypes (1, 2, 3, 5 and 6) were not retained, indicating a selectivity for PDE4. The experimental binding tests on the 6 subtypes of PDE revealed a significant selectivity of εviniferin for the PDE4 subtype. This selectivity was confirmed by evaluation of εviniferin on the secretion of TNF-α and Interleukin-8. Our data demonstrated that εviniferin possesses anti-inflammatory properties by inhibiting PDE4 subtype. In conclusion, reverse pharmacognosy and its inverse docking component cannot only be integrated into a program for new lead discovery but is also a useful approach to find new applications for identified compounds.

Keywords: Inverse docking, cosmetics, cyclic nucleotide phosphodiesterases, viniferin, selnergy