College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang-si 10326, Gyonggi-do, Korea.
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
Molecules. 2021 Aug 30;26(17):5246. doi: 10.3390/molecules26175246.
The pharmacokinetic (PK) change in a drug by co-administered herbal products can alter the efficacy and toxicity. In the circumstances that herb-drug combinations have been increasingly attempted to alleviate Alzheimer's disease (AD), the PK evaluation of herb-drug interaction (HDI) is necessary. The change in systemic exposure as well as target tissue distribution of the drug have been issued in HDIs. Recently, the memory-enhancing effects of water extract of mangosteen pericarp (WMP) has been reported, suggesting a potential for the combination of WMP and donepezil (DNP) for AD treatment. Thus, it was evaluated how WMP affects the PK change of donepezil, including systemic exposure and tissue distribution in mice after simultaneous oral administration of DNP with WMP. Firstly, co-treatment of WMP and donepezil showed a stronger inhibitory effect (by 23.0%) on the neurotoxicity induced by Aβ in SH-SY5Y neuroblastoma cells than donepezil alone, suggesting that the combination of WMP and donepezil may be more effective in moderating neurotoxicity than donepezil alone. In PK interaction, WMP increased donepezil concentration in the brain at 4 h (by 63.6%) after administration without affecting systemic exposure of donepezil. Taken together, our results suggest that WMP might be used in combination with DNP as a therapy for AD.
合并用药的草药产品会改变药物的药代动力学（PK），从而改变疗效和毒性。在越来越多的人试图用草药-药物组合来缓解阿尔茨海默病（AD）的情况下，有必要对草药-药物相互作用（HDI）进行 PK 评估。在 HDI 中，药物的全身暴露和靶组织分布都会发生变化。最近，报道了山竹果皮水提物（WMP）增强记忆的作用，这表明 WMP 与多奈哌齐（DNP）联合用于 AD 治疗具有潜在可能性。因此，评估了 WMP 如何影响多奈哌齐的 PK 变化，包括同时给予 WMP 和多奈哌齐后在小鼠中的全身暴露和组织分布。首先，WMP 与多奈哌齐联合治疗对 Aβ诱导的 SH-SY5Y 神经母细胞瘤细胞神经毒性的抑制作用（强 23.0%）强于多奈哌齐单药治疗，这表明 WMP 与多奈哌齐联合治疗可能比多奈哌齐单药治疗更有效地调节神经毒性。在 PK 相互作用方面，WMP 增加了给药后 4 小时脑内多奈哌齐的浓度（增加 63.6%），而不影响多奈哌齐的全身暴露。综上所述，我们的研究结果表明，WMP 可能与 DNP 联合用于 AD 的治疗。
