Brain regional pharmacokinetics following the oral administration of curcumagalactomannosides and its relation to cognitive function
Brain regional pharmacokinetics following the oral administration of curcumagalactomannosides and its relation to cognitive function
复制标题
DOI：
10.1080/1028415x.2021.1913951
复制
发表时间：
2021-04-20
影响因子：
3.6
通讯作者：
Krishnakumar, I. M.
中科院分区：
文献类型：
--
作者：
Kannan, Ramalingam G.;Abhilash, Maliakal B.;Krishnakumar, I. M.
目的虽然已经报道了许多姜黄素类生物可利用的制剂并作为脑健康营养保健品在商业上销售，但有关其血脑屏障渗透性和脑组织分布的系统信息尚未报道。本研究旨在研究 Wistar 大鼠单剂量和重复剂量口服自乳化食品级姜黄素制剂（使用胡芦巴半乳甘露聚糖水凝胶支架作为“姜黄半乳甘露糖苷”（CGM））后，姜黄素的脑区域药代动力学，以及与未配制的天然姜黄素（NC）相比，其对认知功能的影响。使用超高效液相色谱/电喷雾电离三重四极杆串联质谱 (UPLC-ESI-MS/MS) 系统评估不同时间点的总姜黄素浓度（mg 类姜黄素/kg b. wt.）和重复剂量（100 mg 类姜黄素/kg b. wt.，持续 28 天）。另一组动物也以单剂量（100 mg 类姜黄素/kg 体重）和重复剂量（100 mg 类姜黄素/kg 体重）和重复剂量（100 mg 类姜黄素/kg 体重，持续 28 天）饲喂 CGM，并使用旷场测试和径向臂迷宫进行行为研究。分别为 173.34 +/- 27.12 ng/mL 和 223.22 +/- 32.73 ng/mL。对脑组织的进一步分析表明，血脑屏障具有显着的通透性。脑区域药代动力学（AUC、C（max）和t（1/2））显示相对分布顺序为海马>纹状体>小脑>大脑皮层>脑干。与 NC 相比，补充 28 天的 CGM 还可以显着（p < 0.05）改善运动活动并减少空间记忆错误。 NC治疗也比媒介物治疗组更好地改善了行为。结论CGM可以在单次和重复剂量给药时在大脑中特别是在海马中分布大量的游离姜黄素，消除半衰期为2.6小时。与普通未配制的姜黄素相比，CGM 还显示出对动物行为的积极影响。
ObjectiveThough a number of bioavailable formulations of curcuminoids have been reported and available commercially as nutraceuticals for brain health, systematic informations on their blood-brain-barrier permeability and brain tissue distribution have not been reported. The present study was aimed to investigate the brain regional pharmacokinetics of curcuminoids following both single dose and repeated dose oral administration of a self-emulsifying food-grade formulation of curcuminoids using fenugreek galactomannan hydrogel scaffold as 'curcumagalactomannosides' (CGM), and its influence on cognitive functions in comparison with unformulated natural curcuminoids (NC) in Wistar rats.MethodsCGM was given to animals in single dose (100 mg curcuminoids/kg b. wt.) and repeated dose (100 mg curcuminoids/kg b. wt. for 28 days) and the concentration of total curcuminoids at various parts of brain was evaluated at different time points using Ultra-performance liquid chromatography/electrospray ionization triple quadruple tandem mass spectroscopy (UPLC-ESI-MS/MS) system. Another set of animals were also fed with CGM at single dose (100 mg curcuminoids/kg b. wt.) and repeated dose (100 mg curcuminoids/kg b. wt. for 28 days) and the behavioural studies were conducted using open field test and radial arm maze.ResultsUPLC-ESI-MS/MS analyses of plasma revealed significant absorption of unconjugated (free) curcuminoids upon both single and repeated dose administration of CGM with maximum concentrations of 173.34 +/- 27.12 ng/mL and 223.22 +/- 32.73 ng/mL, respectively. Further analysis of brain tissues demonstrated significant blood-brain-barrier permeability. Brain regional pharmacokinetics (AUC, C (max) and t (1/2)) indicated a relative distribution order of hippocampus > striatum > cerebellum > cerebral cortex > brain stem. Supplementation of CGM for 28 days also offered significant (p < 0.05) improvement in locomotor activity and reduction in spatial memory errors as compared to NC. The NC treatment also improved the behaviour better than the vehicle-treated group.ConclusionCGM could distribute significant amount of free curcuminoids, in brain especially in the hippocampus at both single and repeated dose administration with an elimination half-life of 2.6 h. CGM also showed a positive impact in behaviour of animals in comparison with normal unformulated curcuminoids.