Biotransformation of the promising neuro-regenerative hop chalcone Xanthohumol C

The prenylated chalcone xanthohumol C from Humulus lupulus L. -hops- was identified as an inducer of neuronal lineage-specific differentiation of neuronal stem cells [1]. Furthermore, a structure-activity study revealed that a pyrano ring is a structural characteristic responsible for the neuro-differentiation effect and that the unknown targets respond to structural changes [2]. Since the induction of neuronal-differentiation is the key mechanism concerning a therapy for neurodegenerative diseases using the body’s own regeneration mechanism, xanthohumol C, is a promising candidate for further pharmaceutical evaluation.

To evaluate the potential of xanthohumol C as a drug candidate, studies concerning absorption, distribution and metabolism are needed. Recently, a formulation of xanthohumol C in cyclodextrin was characterized and enhanced water solubility was determined. Furthermore, a small animal study showed that the compound is absorbed in this formulation and reaches the brain as target [3]. To the best of our knowledge, there is only little known about biotransformation of this promising candidate. Accordingly, human microsomes were used to metabolize xanthohumol C and HPLC/MS analysis showed that xanthohumol C was transformed into four main metabolites by cytochrome monooxygenases p450 (CYPs). Using mostly selective inhibitors and a synthesized isotope labelled internal standard, the CYPs 2C8, 2C19 and 2D6 were identified as possible main metabolizers.

• References

• 1 Oberbauer E, Urmann C, Steffenhagen C, Bieler L, Brunner D, Furtner T. et al J Nutr Biochem; 2013; 24: 953-1962
• 2 Urmann C, Kirchinger M, Bieler L, Couillard-Despres S, Aigner L, Riepl H. Structural modification of xanthohumol C and the effect on inducing differentiation in neural precursor cells. Planta Medica 2015; 81 SL5: C-05.
• 3 in review.