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

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.

Identification of Key Pathways and Targets of Kai Xin San in The Treatment of Alzheimer's Disease Based On a Network Pharmacology Approach and Experimental Validation

“…It was reported that Jia Wei Kai Xin San alleviated cognitive de cits and improved cholinergic neurotransmission function via modulating Aβ levels in hippocampus of Aβ-injection mice [50]. Moreover, Na Wang et al demonstrated that KXS restored the cognitive impairment and prevented the hippocampus neuronal damage induced by Aβ 42 in rats via increasing the level of neprilysin and accelerating the degradation of Aβ [51].…”

Quercetin‐3‐O‐Glucuronide Alleviates Cognitive Deficit and Toxicity in Aβ1‐42‐Induced AD‐Like Mice and SH‐SY5Y Cells

“…Aβ 1‐42 ‐infusion model, which was based on the Aβ cascade hypothesis, was a useful supplement to transgenic mouse models [ 43,44 ] and it was used in many previous studies. [ 45–47 ] Moreover, this model could be used to explore the Aβ‐induced pathological changes, including brain IR. [ 48 ] In our research, the i.c.v.…”

Senegenin Inhibits Aβ1-42-Induced PC12 Cells Apoptosis and Oxidative Stress via Activation of the PI3K/Akt Signaling Pathway

“…Aβ 1–42 was dissolved in PBS and incubated at 37°C for seven days to induce aggregation. 45 , 46 Next, the aggregated Aβ 1–42 was diluted to the desired concentration. A 2mM stock solution of Sen was prepared by dissolving 20mg Sen powder in 15mL DMEM and placed at −20°C for long-term storage.…”