Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (5): 794-804.doi: 10.4103/1673-5374.249227

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Kai Xin San ameliorates scopolamine-induced cognitive dysfunctio

Yu-Min Xu 1, 2 , Xin-Chen Wang 3 , Ting-Ting Xu 1 , Hong-Ying Li 1 , Shang-Yan Hei 1 , Na-Chuan Luo 1 , Hong Wang 1 , Wei Zhao 1 , Shu-Huan Fang 1 , Yun-Bo Chen 1 , Li Guan 1 , Yong-Qi Fang 4 , Shi-Jie Zhang 1, 5 , Qi Wang 1, 6, Wei-Xiong Liang 1, 6   

  1. 1 Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
    2 First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan Province, China
    3 School of Food and Pharmaceutical Engineering, Zhaoqing University, Zhaoqing, Guangdong Province, China
    4 First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
    5 Department of Neurology, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
    6 Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong Province, China
  • Online:2019-05-15 Published:2019-05-15
  • Contact: Shi-Jie Zhang, MD, PhD, zsj19891122@gmail.com; Qi Wang, MD, wangqi@gzucm.edu.cn; Wei-Xiong Liang, MD, liangwx@yeah.net.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81473740, 81673627, 81673717 (to QW); Guangzhou Science Technology and Innovation Commission Technology Research Projects, China, No. 2018050100 (to QW); the Foundation for Characteristic Innovation of Educational Commission of Guangdong Province, China, Grant No. 2016KTSCX011 (to SHF); the Open Tending Project for Construction of High-Level University, Guangzhou University of Chinese Medicine, China, No. 34 and 118, 2017 (to SHF); the Technology Platform of Clinical Trials on New Traditional Medicine, China, No. 2012ZX09303009-003 (to WXL); the Technology Platform of Clinical Evaluation on New Traditional Medicine, China, No. 2008ZX09312-021 (to WXL).

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Abstract:

Kai Xin San (KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups (which received physiological saline), the doses of KXS (0.7, 1.4 and 2.8 g/kg per day) and donepezil (3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopol¬amine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were mea¬sured. The results confirmed the following. (1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze. (2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze. (3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies. (4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus. (5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and re¬duced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.

Key words: Kai Xin San, cognitive dysfunction, scopolamine hydrobromide, neuroprotection, oxidative stress, synaptic dysfunction, apoptosis, cholinergic system dysfunction, donepezil, neural regeneration