Investigation of the improvement effect of Dihuang yinzi on neurological function of APP/PS1 double transgenic positive mice based on gut-brain axis and its mechanism
- VernacularTitle:基于肠脑轴探讨地黄饮子对APP/PS1转基因阳性小鼠神经功能的改善作用及机制
- Author:
Jing CHEN
1
;
Xicai LIANG
2
;
Jian WANG
2
;
Shenghua WANG
2
;
Tianyi NING
2
Author Information
1. Teaching Experiment Center of Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China
2. Experimental Animal Center of Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China
- Publication Type:Journal Article
- Keywords:
Dihuang yinzi;
gut-brain axis;
neurological
- From:
China Pharmacy
2022;33(24):2978-2984
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the improvement effect of Dihuang yinzi on neurological function of APP/PS1 double transgenic positive mice and its possible mechanism. METHODS APP/PS1 double transgenic positive mice were randomly divided into APP/PS1 positive model group, Dihuang yinzi low-dose, medium-dose and high-dose groups (12, 24, 48 g/kg,by the amount of crude drug), western medicine group (donepezil hydrochloride 0.8 mg/kg); APP/PS1 transgenic negative mice were included in as APP/PS1 negative normal group, with 6 mice in each group. Administration groups were given relevant medicine intragastrically; APP/PS1 positive model group and APP/PS1 negative normal group were given constant volume of normal saline intragastrically, once a day, for consecutive 28 d. After the last medication, the ability of learning and memory, intestinal flora diversity (only medium-dose group of Dihuang yinzi), pathological changes of neural cells in hippocampus, and the expressions of Bcl-2, Bax and brain-derived neurotrophic factor (BDNF) in mice of each group were investigated. RESULTS Compared with APP/PS1 positive model group, escape latency of mice was shortened significantly in Dihuang yinzi medium-dose and high-dose groups, while the times of crossing the platform significantly increased (P<0.05). Compared with APP/PS1 positive model group, Chao1 index of Dihuang yinzi medium-dose group was lower, while Shannon index was higher (P<0.05); OTU abundance of microbial flora was decreased to some extent; dominant flora was Clostridia o_ Clostridia_ vadinBB60_ Group, verruca G_ UCG_ 005. Compared with the APP/PS1 positive model group, the pathological changes of the nerve cells in the hippocampal CA1 area of mice were improved in the medium-dose and high-dose groups of Dihuang yinzi; the protein expressions of Bcl-2 and BDNF in the hippocampal tissue were significantly increased, while the protein expression of Bax was significantly decreased (P<0.05). CONCLUSIONS Dihuang yinzi can enhance the diversity of flora, change the type of dominant flora, and can inhibit the apoptosis of brain neurons, and increase the level of BDNF; its mechanism may be to protect nerve cells by means of gut-brain axis, thereby improving the learning and memory ability of APP/PS1 positive model mice.