Pharmacokinetics of Nuciferine and N-Nornuciferine, Two Major Alkaloids From Leaves, in Rat Plasma and the Brain.

The leaf of the lotus () is a natural plant resource used as both food and herbal medicine (He-Ye) in China. Alkaloids are considered the major bioactive compound of the herb and exhibit various biological activities, including anti-hyperlipidemia, anti-obesity, anti-inflammatory, and anti-hyperuricemic effects. Nuciferine (NF) and N-nuciferine (N-NF) are two major alkaloids found in the herb. In the present work, the plasma and brain pharmacokinetics of the two compounds were investigated after oral and intravenous () administration of a lotus leaf alkaloid fraction to SD rats via ultra-performance liquid chromatography coupled with photodiode array detection and brain microdialysis. After oral administration (50 mg/kg), the two compounds NF and N-NF were rapidly absorbed into the blood and reached a mean maximum concentration () of 1.71 μg/mL at 0.9 h and 0.57 μg/mL at 1.65 h, respectively. After administration (10 mg/kg), NF and N-NF were found to have a relatively wide volume of distribution (, 9.48 and 15.17 L/kg, respectively) and slow elimination half-life (, 2.09 and 3.84 h, respectively). The oral bioavailability of NF and N-NF was estimated as 58.13% and 79.91%, respectively. After dosing (20 mg/kg), the two compounds rapidly crossed the blood-brain barrier and reached their (in unbound form): 0.32 and 0.16 μg/mL at 0.89 and 1.22 h, respectively. Both alkaloids had widespread distribution in the brain, with /-values of 19.78 L/kg and 16.17 L/kg, respectively. The mean values of NF and N-NF in the brain were 1.24 and 1.39 h, respectively. These results can help us to better understand the characteristics and neuro-pharmacological effects of the lotus alkaloid fraction.