Liu Wei, Zhu Yudan, Wang Yongli, Qi Shenglan, Wang Yuwen, Ma Chao, Li Shuping, Jiang Bo, Cheng Xuemei, Wang Zhengtao, Xuan Zhenyu, Wang Changhong
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China; Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China.
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China.
J Ethnopharmacol. 2017 May 23;204:95-106. doi: 10.1016/j.jep.2017.04.019. Epub 2017 Apr 23.
Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear.
The present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches.
The acetylcholinesterase (AChE) inhibitory activities of extract (EXT), alkaloid fraction (ALK) and flavonoid fraction (FLA) from APP were evaluated in normal male C57BL/6 mice. The anti-amnesic effects of EXT and ALK from APP were measured in scopolamine-induced memory deficits mice by the Morris water maze (MWM) tasks. The levels of biomarkers, enzyme activity and protein expression of cholinergic system were determined in brain tissues.
The AChE activity was significantly decreased and the content of neurotransmitter acetylcholine (ACh) was significantly increased in normal mice cortex and hippocampus by treatment with donepezil at dosage of 8mg/kg, EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P<0.05), and the AChE activity and the content of ACh were not significantly changed in cortex and hippocampus after treatment with FLA at dosages of 10, 30, 90mg/kg (P>0.05). In the MWM task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by treatment with EXT at dosages of 550, 1650mg/kg and ALK at dosages of 30, 90mg/kg (P<0.05). Moreover, the activity and protein expression of AChE was significantly decreased and the content of neurotransmitter ACh was significantly increased in cerebral cortex of scopolamine-induced mice by treatment with EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P<0.05), compared with scopolamine-treated group.
EXT and ALK from APP exert beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. APP is an effective traditional folk medicine and the ALK fraction is proved to be the main effective components for the treatment of forgetfulness. The ALK may be valuable source for lead compounds discovery and drug development for treatment of memory impairment such as in Alzheimer's disease.
骆驼蓬地上部分在中国维吾尔医学中作为传统草药用于治疗健忘症。但其活性成分及潜在机制尚不清楚。
本研究旨在探讨骆驼蓬地上部分提取物和生物碱部位对东莨菪碱诱导的认知功能障碍的改善作用，并阐明其潜在作用机制，为其民间应用提供科学依据，为进一步研究奠定基础。
在正常雄性C57BL/6小鼠中评估骆驼蓬地上部分提取物（EXT）、生物碱部位（ALK）和黄酮部位（FLA）的乙酰胆碱酯酶（AChE）抑制活性。通过莫里斯水迷宫（MWM）任务检测骆驼蓬地上部分EXT和ALK对东莨菪碱诱导的记忆缺陷小鼠的抗遗忘作用。测定脑组织中生物标志物水平、胆碱能系统的酶活性和蛋白表达。
在正常小鼠皮层和海马中，8mg/kg多奈哌齐、183、550、1650mg/kg的EXT以及10、30、90mg/kg的ALK处理后，AChE活性显著降低，神经递质乙酰胆碱（ACh）含量显著增加（P<0.05）；而10、30、90mg/kg的FLA处理后，皮层和海马中的AChE活性和ACh含量无显著变化（P>0.05）。在MWM任务中，550、1650mg/kg的EXT以及30、90mg/kg的ALK处理可显著逆转东莨菪碱诱导的目标区域内游泳时间和平台放置处穿越次数的减少（P<0.05）。此外，与东莨菪碱处理组相比，183、550、1650mg/kg的EXT以及10、30、90mg/kg的ALK处理可使东莨菪碱诱导小鼠大脑皮层中AChE的活性和蛋白表达显著降低，神经递质ACh含量显著增加（P<0.05）。
骆驼蓬地上部分的EXT和ALK对东莨菪碱诱导的记忆损伤小鼠的学习和记忆过程具有有益作用。骆驼蓬是一种有效的传统民间药物，生物碱部位被证明是治疗健忘症的主要有效成分。生物碱可能是发现治疗记忆损伤（如阿尔茨海默病）先导化合物和开发药物的宝贵来源。
