Park Keontae, Lee Won Hyung, Cho Eunbi, Kong Chang Hyeon, Min Hoo Sik, Kim Min Seo, Han Ju Eun, Jung Seo Yun, Kim Dong Hyun, Ryu Jong Hoon
Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, 02447, Republic of Korea.
Department of Pharmacology, School of Medicine, Konkuk University, Seoul, 05029, Republic of Korea.
J Ethnopharmacol. 2025 Mar 13;343:119500. doi: 10.1016/j.jep.2025.119500. Epub 2025 Feb 13.
Cheonwangbosim-dan (CWBSD) as a traditional herbal medicine prescription has been used for cognitive dysfunction in terms of heart blood deficiency, however, there were few researches for cognitive dysfunction and its mode of action.
This study was aimed to examine the effects of CWBSD on hypocholinergic-induced memory impaired mice and unveil its mechanism of action on cognitive function.
The standardized CWBSD was used in the present study. Several behavioral tests, including Y-maze task, the Morris water maze task (MWM), novel object recognition test (NORT) and passive avoidance test (PAT), were employed with administration of CWBSD (150, 500 or 1500 mg/kg) in scopolamine-treated mice. After behavioral tests, the mice were sacrificed and the Western blot analysis and electrophysiological analysis were conducted to investigate the mechanism of CWBSD on ameliorating cognitive function.
The administration of CWBSD improved cognitive functions measured by the Y-maze task, MWM, NORT and PAT in scopolamine-induced cognitive impaired mice. This memory improvement effect was associated with the activation of protein kinase C zeta (PKCζ)/calcium-calmodulin-dependent protein kinase Ⅱ (CaMKⅡ)-extracellular signal-regulated kinase (ERK)-cAMP response element-binding protein (CREB)-brain-derived neurotropic factor (BDNF) pathway via N-methyl-D-aspartate receptor subtype 2B (NR2B), and the activation of this pathway increased long-term potentiation in the brain of mice.
The administration of CWBSD could ameliorate spatial memory, recognition memory and long-term memory, and such ameliorating activities would be derived from the activation of NMDA receptor-associated pathway with increase of LTP in the brain. These results suggests that CWBSD would be a candidate for a new dementia treatment.
天王补心丹（CWBSD）作为一种传统草药方剂，已被用于治疗心血虚所致的认知功能障碍，然而，针对认知功能障碍及其作用机制的研究较少。
本研究旨在探讨天王补心丹对胆碱能功能低下诱导的记忆受损小鼠的影响，并揭示其对认知功能的作用机制。
本研究使用了标准化的天王补心丹。在东莨菪碱处理的小鼠中，给予天王补心丹（150、500或1500mg/kg）后，进行了多项行为学测试，包括Y迷宫任务、莫里斯水迷宫任务（MWM）、新物体识别测试（NORT）和被动回避测试（PAT）。行为学测试后，处死小鼠并进行蛋白质免疫印迹分析和电生理分析，以研究天王补心丹改善认知功能的机制。
给予天王补心丹可改善东莨菪碱诱导的认知受损小鼠在Y迷宫任务、MWM、NORT和PAT中所测量的认知功能。这种记忆改善作用与通过N-甲基-D-天冬氨酸受体2B亚型（NR2B）激活蛋白激酶Cζ（PKCζ）/钙调蛋白依赖性蛋白激酶Ⅱ（CaMKⅡ）-细胞外信号调节激酶（ERK）-环磷酸腺苷反应元件结合蛋白（CREB）-脑源性神经营养因子（BDNF）通路有关，该通路的激活增加了小鼠大脑中的长时程增强。
给予天王补心丹可改善空间记忆、识别记忆和长期记忆，这种改善作用源于NMDA受体相关通路的激活以及大脑中LTP的增加。这些结果表明天王补心丹可能是一种新型痴呆治疗药物的候选药物。
