Secondary metabolites from lichen as potent inhibitors of advanced glycation end products and vasodilative agents

Andreas Schinkovitz (1) , Pierre Le Pogam (2) , Séverine Derbré (1) , Emilie Vessieres (3, 4) , Patricia Blanchard (5, 6, 1) , Sangeetha-Laura Thirumaran (5, 6) , Dimitri Bréard (5, 6, 1) , Marie-Christine Aumond (5, 6, 1) , Martin Zehl (7) , Ernst Urban (7) , Amandeep Kaur (7) , Nathalie Jäger (7) , Stefanie Hofer (5, 6) , Brigitte Kopp (7) , Hermann Stuppner (8) , Isabelle Baglin (5, 6, 1) , Denis Seraphin (5, 6, 1) , Sophie Tomasi (2) , Daniel Henrion , Joël Boustie (2) , Pascal Richomme (5, 6, 1)

1 SONAS - Substances d'Origine Naturelle et Analogues Structuraux
2 ISCR - Institut des Sciences Chimiques de Rennes
3 MITOVASC - MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale
4 BNMI - Biologie Neurovasculaire et Mitochondriale Intégrée
5 UA - Université d'Angers
6 QUASAV - SFR UA 4207 QUAlité et SAnté du Végétal
7 TU Wien - Vienna University of Technology
8 Leopold Franzens Universität Innsbruck - University of Innsbruck

Secondary metabolites from lichens are known for exhibiting various biological effects such as anti-inflammatory, antioxidant and antibacterial activities. Despite this wide range of reported biological effects, their impact on the formation of advanced glycation end products (AGEs) remains vastly unexplored. The latter are known contributors to lifestyle and age-related diseases such as Alzheimer and Parkinson. Moreover, the development of atherosclerosis and arterial stiffness is causally linked to the formation of AGEs. With this in mind, the present work evaluated the inhibitory effects of secondary lichen metabolites on the formation of pentosidine-like AGEs by using an in vitro, Maillard reaction based, fluorescence assay. Overall, thirty-seven natural and five synthetically modified compounds were tested, eighteen of which exhibiting IC values in the range of 0.05 to 0.70 mM, which corresponds to 2 to 32 fold of the inhibitory activity of aminoguanidine. In addition, all compounds were evaluated on their radical scavenging capacities in an DPPH assay targeting one major inhibiting mechanism of AGEs formation. Furthermore, as both AGEs' formation and hypertension are major risk factors for atherosclerosis, compounds that were available in sufficient amounts were also tested for their vasodilative effects. Although some of the active compounds were previously reported cytotoxic, present results highlight the interesting potential of secondary lichen metabolites as anti-AGE and vasodilative agents.

Keywords: Inhibition of Advanced Glycation End Products; Declarations of interest none.; Vasodilation; Lichen metabolites; Maillard reaction; Radical scavenging

Domains: Chemical Sciences; Medicinal Chemistry; Life Sciences [q-bio]; Pharmaceutical sciences

Andreas Schinkovitz, Pierre Le Pogam, Séverine Derbré, Emilie Vessieres, Patricia Blanchard, et al.. Secondary metabolites from lichen as potent inhibitors of advanced glycation end products and vasodilative agents. Fitoterapia, 2018, 131, pp.182-188. ⟨10.1016/j.fitote.2018.10.015⟩. ⟨hal-01903310⟩