Jia-Wei-Kai-Xin-San, an Herbal Medicine Formula, Ameliorates Cognitive Deficits via Modulating Metabolism of Beta Amyloid Protein and Neurotrophic Factors in Hippocampus of Aβ1-42 Induced Cognitive Deficit Mice.

Yue Zhu,Yiwei Shi,Ziqiang Zhu,Mengqiu Liu,Cheng Cao,Zhenxiang Han,Dawei Qian,Mingzhu Qi,Renjie Huang,Jin-Ao Duan

doi:10.3389/fphar.2019.00258

Yue Zhu, Yiwei Shi + Show 8 more

Open Access

https://doi.org/10.3389/fphar.2019.00258

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Abstract

Jia-Wei-Kai-Xin-San (JWKXS) is a Chinese medicine formula applied for treating morbid forgetfulness in ancient China. Today, this formula is frequently applied for Alzheimer’s disease and vascular dementia (VD) in clinic. Here, we developed it as granules and aimed to evaluate its anti-AD effect on β amyloid protein 1–42 (Aβ1-42) induced cognitive deficit mice and reveal the possible molecular mechanisms. Firstly, daily intra-gastric administration of chemically standardized of JWKXS granules for 7 days significantly ameliorated the cognitive deficit symptoms and inhibited cell apoptosis in hippocampus on Aβ1-42 injection mice. JWKXS granules significantly decreased Aβ level, increased superoxide dismutase activity and decreased malondialdehyde level in hippocampus of model mice. It also restored acetylcholine amounts, inhibited acetylcholinesterase activities and increased choline acetyltransferase activities. In addition, JWKXS granules enabled the transformation of precursors of NGF and BDNF into mature forms. Furthermore, JWKXS granules could regulate gene expressions related to Aβ production, transportation, degradation and neurotrophic factor transformation, which led to down-regulation of Aβ and up-regulation of NGF and BDNF. These findings suggested that JWKXS granules ameliorated cognitive deficit via decreasing Aβ levels, protecting neuron from oxidation damages and nourishing neuron, which could serve as alternative medicine for patients suffering from AD.

Highlights

Alzheimer’s disease is the highest incidence dementia in aging society
After JWKXS treatments at two dosages, the latency and distance of mice were decreased significantly compared with model group mice (p < 0.05), which was close to the level of sham group, and displayed the strengthened learning abilities
The tendency of JWKXS was in line with that of huperzine A treatment, which implied that JWKXS possessed the ability of ameliorating cognitive deficits in model mice due to Aβ injection into hippocampus

Summary

Introduction

It is estimated that 40 million people have dementia worldwide and most of them are older than 60 years. According to a report made by Alzheimer’s Association, AD has become the sixth leading cause of death in the United States and this figure is estimated to be double every 20 years, until at least 2050 (Alzheimer’s Association, 2018). As to genetic cause, carrying ApoE4 gene and gene mutations of amyloid precursor protein (APP), presenilins 1 and 2 greatly enhance AD susceptibility. In addition to genetic mutation, pathological factors including vascular disease, diabetes, obesity, depression greatly enhance AD risk. Not limited to the genetic and pathological factors, low education degree and unhealthy life style such as mental, physical inactivity, and smoking increase AD susceptibility (Scheltens et al, 2016)

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