Evaluation of the routes of piperine administration on brain permeability of [F-18]fluoropropylcurcumin

Objectives Curcumin, a major component of curry spice, has been extensively studied for its anticancer, antioxidant, antiinflammatory, and antiamyloidogenic activities. We reported that [F-18]fluoropropylcurcumin ([F-18]FP-curcumin) has excellent binding affinity for β-amyloid aggregates (Ki = 0.07 nM) but relatively low brain permeability. In this study, therefore, we evaluated the brain permeability of [F-18]FP-curcumin in terms of the route of piperine administration, because piperine is found to increase serum concentrations of curcumin to 154% in rats and to 2000% in humans.

Methods [F-18]FP-curcumin was synthesized using a known method. Piperine was administered into ICR mice via three different routes; (oral) [F-18]FP-curcumin was injected into mice at 30 min after the oral administration of piperine (20 mg/kg) either in rice bran oil or in water; (i.p.) [F-18]FP-curcumin was injected into mice at 30 min after the i.p. administration of piperine (20 mg/kg) in rice bran oil; (i.v.) [F-18]FP-curcumin was co-injected with piperine (2 mg/kg) into mice via a tail vein. The mice were sacrificed at 2 min post-injection, and tissues were removed, weighed, and counted. In control experiment, ICR mice were injected with [F-18]FP-curcumin, sacrificed at 2 and 30 min post-injection, and treated as above.

Results Tissue distribution of [F-18]FP-curcumin showed radioactivity accumulation in the liver (27.78% ID/g), blood (5.92% ID/g), intestine (3.39% ID/g), and brain (0.80% ID/g) at 2 min in control mice. The initial brain uptake of [F-18]FP-curcumin increased to 1.22% ID/g (153%) and the liver uptake decreased to 19.14% ID/g (68%) by i.v. injection with piperine, relative to a value of 100% in control mice. Tissue distribution of [F-18]FP-curcumin by both oral and i.p. administration of piperine was comparable to that of control mice.

Conclusions This result suggests that the i.v. injection of [F-18]FP-curcumin with piperine is a better route of administration than the others in terms of its brain permeability