Curcuminoids are the main bioactive components of the well-known Asian spice and traditional
medicine, turmeric [1]. These compounds have poor bioavailability, in vivo they undergo a rapid metabolism, and bioreduced derivatives are among their main
in vivo metabolites. These metabolites were also reported to exert various bioactivities
in vitro and in vivo [2]. They can be synthetized by batch hydrogenation, however this method has low selectivity
[3].
Our objective was to develop a procedure to selectively obtain curcuminoids with different
levels of saturation by using a continuous flow hydrogenation reactor. Furthermore,
we aimed to evaluate pharmacokinetic properties of the prepared metabolites, such
as kinetic solubility, chemical and metabolic stability, and their gastrointestinal
and blood-brain barrier permeability with parallel artificial membrane permeability
assay (PAMPA).
To this end, we achieved high selectivity in preparing hexahydrocurcumin. The pharmacokinetic
tests showed that the reduced metabolites have dramatically increased water solubility
and chemical stability as compared to that of curcumin. The metabolic rate by human
liver microsomes followed the tetrahydrocurcumin > curcumin ~ hexahydrocurcumin ≫
octahydrocurcumin order. Curcumin showed negligible BBB and GI penetration, similarly
to hexahydrocurcumin, tetrahydrocurcumin was however largely superior in this regard.
Our results show better bioavailability and pharmacokinetic properties for some hydrogenated
curcuminoid derivatives as compared to those of curcumin.
