Humulus lupulus L. is a traditional medicinal plant and was already mentioned by Mesue (died 1015). Beside bitter acids, prenylated flavonoids are partly responsible for manifold biological activities such as anti-cancer, neuroprotective activity as well as induction of differentiation. A possible link between these effects is the epigenetic and, in particular, the histone deacetylase (HDACs) [1]. The group of HDACs deacetylates the lysine on the terminal end of histones and therfore prepare the DNA for subscription.
In this study the inhibition of HDACS by prenylated flavonoids was determined. In the screening, the sum of HDACs were used, which were obtained by nuclear extraction of HeLa cells.
Figure: Inhibition of HDACs of HeLa cells nuclear extract by prenylflavonoides (c=50 µM) compared to Trichostin A (c=10 µM) and structures of compounds tested.
Xanthohumol, which is known as a potent influencer of cancerogensis shows the lowest inhibition rate. 8-prenylnaringenin [2], the most active phytoestrogen known thus far, shows an inhibition of approximatley 10 %. The most potent inhibitor of the HDACs is xanthohumol C which was recently identified as a potent inducer of neurogenesis in neuronal stem cells [3]. Since it is known, that the induction of differentiation and neuroprotection is partly linked to the activity of different HDACs, the effect of xanthohumol C on several recombinant enzymes was further investigated.
[1] Marks P, Richon V., Rifkind, R. J Natl Cancer 2000; 92: 1210-1216.
[2] Oberbauer E, Urmann C, Steffenhagen C, Bieler L, Furtner T, Humpel C, Baumer B, Bandtlow C, Couillard-Despres S, Rivera FJ, Riepl H, Aigner L. J Nutr Biochem 2013; 24: 1953-1962.
[3] Urmann C, Oberbauer E, Couillard-Despres S, Aigner L, Riepl H. Planta Med 2015: 4: 305-311.