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

Abstract

The leaf of the lotus (Nelumbo nucifera) 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 (i.v.) 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 (Cmax) of 1.71 μg/mL at 0.9 h and 0.57 μg/mL at 1.65 h, respectively. After i.v. administration (10 mg/kg), NF and N-NF were found to have a relatively wide volume of distribution (Vd, λz, 9.48 and 15.17 L/kg, respectively) and slow elimination half-life (t1/2, λz, 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 i.v. dosing (20 mg/kg), the two compounds rapidly crossed the blood–brain barrier and reached their Cmax (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 Vd, λz/F-values of 19.78 L/kg and 16.17 L/kg, respectively. The mean t1/2, λz 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.

Simultaneous Determination of Five Alkaloids by HPLC-MS/MS Combined With Micro-SPE in Rat Plasma and Its Application to Pharmacokinetics After Oral Administration of Lotus Leaf Extract

“…A few studies on one or two alkaloid of lotus leaf in pharmacokinetic study have been reported (Gu et al, 2014; Xu et al, 2015; Geng et al, 2018; Ye et al, 2018). Comparisons of the present work with other reported method are listed in Table 6 in detail: First, compared with consumption of organic solvent in this work, there were less organic solvent in these reports (Xu et al, 2015; Geng et al, 2018).…”

“…Liriodenine, O-nornuciferin, and armepavine exhibit the activities of antioxidant and antimicrobia antifibrotic (Costa et al, 2010; Weng et al, 2012). In addition, there were only a few reports for pharmacokinetic studies of one or two alkaloid compounds after oral administration of lotus leaf extract (Gu et al, 2014; Xu et al, 2015; Geng et al, 2018; Ye et al, 2018). However, the pharmacokinetic property of one or two alkaloids does not represent the metabolic regulation of the whole lotus leaf in vivo .…”

The Latest Studies on Lotus (Nelumbo nucifera)-an Emerging Horticultural Model Plant

“…In the last decade, it is becoming more and more popular as weight-losing tea in China to reduce the level of lipids in the human body [79]. Studies have shown that alkaloids are the major bioactive compounds in lotus leaves, with nuciferine and N-nornuciferine being the major two [80,81,82]. To evaluate the biosynthesis pathway of alkaloids and its regulation in lotus leaf, several transcriptomic studies were performed [83,84], which revealed that a benzylisoquinoline alkaloids (BIA) biosynthetic pathway and its transcriptional regulation differ in high BIAs lotus compared with low BIAs lotus [84].…”

Antioxidant Potential and the Characterization of Arachis hypogaea Roots

“…Peak numbers 3,9,12,15,18,20,23,24,25,31 and 36 represent different flavonoids and their derivatives with numerous health beneficial properties including antioxidant, anticancer, anti-inflammatory, antidiabetic and antimicrobial properties [36]. 2-Methoxy cinnamic acid (peak 5, m/z: 178.195) is a bioactive derivative of cinnamic acid and metabolite of tyrosinase inhibitor and had shown anti-inflammatory, antipyretic, and analgesic properties [37].…”

“…B; 24 min, 55% B; 28 min, 75% B; and 32 min, 90% B. e final condition was maintained for the next 8 minutes[18].2.6. Statistical Analysis.All experiments were conducted in triplicate, and one-way analysis of variance using Tukey's multiple comparison tests was performed.…”