The effects of Cheonwangbosim-dan, a traditional herbal medicine prescription, on scopolamine-induced cognitive dysfunction in mice

IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Journal of ethnopharmacology Pub Date : 2025-02-13 DOI:10.1016/j.jep.2025.119500
Keontae Park , Won Hyung Lee , Eunbi Cho , Chang Hyeon Kong , Hoo Sik Min , Min Seo Kim , Ju Eun Han , Seo Yun Jung , Dong Hyun Kim , Jong Hoon Ryu
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Abstract

Ethnopharmacological relevance

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.

Aim of the study

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.

Materials and methods

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.

Results

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.

Conclusion

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.

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中药复方天王保心丹对东莨菪碱所致小鼠认知功能障碍的影响
川王保心丹作为一种传统中药方剂,已被用于治疗心虚认知功能障碍,但对其认知功能障碍及其作用方式的研究较少。本研究旨在探讨CWBSD对低胆碱能性记忆损伤小鼠的影响,揭示其对认知功能的作用机制。材料与方法本研究采用标准化的CWBSD。在东莨菪碱处理小鼠中分别给予150、500或1500 mg/kg的CWBSD,进行y迷宫任务、Morris水迷宫任务(MWM)、新目标识别测试(NORT)和被动回避测试(PAT)。行为学实验结束后,处死小鼠,采用Western blot和电生理分析方法探讨CWBSD改善认知功能的作用机制。结果东莨菪碱对y型迷宫任务、MWM、NORT和PAT测量的认知功能有改善作用。这种记忆改善作用与蛋白激酶Cζ (PKCζ)/钙钙调素依赖性蛋白激酶Ⅱ(CaMKⅡ)-细胞外信号调节激酶(ERK)-cAMP反应元件结合蛋白(CREB)-脑源性神经营养因子(BDNF)通路通过n-甲基-d -天冬氨酸受体亚型2B (NR2B)激活有关,该通路的激活增加了小鼠脑内的长期增强。结论给药CWBSD可改善大鼠空间记忆、识别记忆和长时记忆,其作用机制可能与NMDA受体相关通路的激活和LTP的升高有关。这些结果表明,CWBSD可能是一种新的痴呆症治疗方法。
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来源期刊
Journal of ethnopharmacology
Journal of ethnopharmacology 医学-全科医学与补充医学
CiteScore
10.30
自引率
5.60%
发文量
967
审稿时长
77 days
期刊介绍: The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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