Qingxin kaiqiao fang ameliorates memory impairment and inhibits apoptosis in APP/PS1 double transgenic mice through the MAPK pathway

Abstract

Background

Qingxin kaiqiao fang (QKF) has been found to treat Alzheimer’s disease (AD) through apoptosis inhibition. The mitogen-activated protein kinase (MAPK) pathway is closely related to apoptosis in the course of AD. This study aimed to investigate whether QKF-induced apoptosis depression is achieved through MAPK pathway.

Materials and methods

C57BL/6 J and APP/PS1 mice were used as control and model groups. APP/PS1 mice were treated with different dosages of QKF (4.75, 9.5, and 19 g⋅kg⁻¹⋅d⁻¹⋅ig, respectively) for 12 weeks as L-QKF, M-QKF, and H-QKF groups. The M-QKF-treated APP/ PS1 mice were administrated with 2 µg/kg of U46619 and saline, intra ventricular ventricle injection, as M-QKF+U46619 and M-QKF+saline groups and were injected with PD98059 0.3 mg/kg and the same volume of dimethyl sulfoxide (DMSO), intravenous, as M-QKF+PD98059 and M-QKF+DMSO groups. After 12 weeks treatment, Morris water maze was performed for behavior study. Pathological degeneration was examined by H&E staining, Nissl staining, and transmission electron microscope observation of hippocampus; immunohistochemistry and Western blot (WB) were tested for amyloid β (Aβ) expression. Apoptosis was measured through TUNEL assay; Bax, Bcl-2, and caspase-3 expression through WB; and cleaved caspase-3 expression through ELISA. MAPK pathway was detected via WB for the expressions of ERK1/2, JNK, and p38 MAPK and their phosphorylation patterns.

Results

QKF improved the learning and memory capability, as well as inhibited neuronal apoptosis and then reduced the pathological degeneration of APP/PS1 mice. M-QKF reduced neuron apoptosis by inhibiting p38 MAPK and activating ERK1/2 but had no significant effect on JNK.

Conclusion

QKF, especially at the middle dose, alleviated the learning and memory impairment and played an antiapoptotic role in AD through MAPK pathways.

Keywords:

• Qingxin kaiqiao
• Alzheimer’s disease
• apoptosis
• APP
• PS1 mice
• MAPK

Acknowledgments

This work was supported by grants from Natural Science Foundation of China (No.81573896 to Haiyan Hu, No. 81601705 to Kailiang Zhou); Zhejiang Provincial Medicine and Health Technology Project (No. LY15H270016 to Haiyan Hu, No. 2017KY472 to Kailiang Zhou). Center of Cryo-Electron Microscopy Zhejiang University provided experimental platform.

Author contributions

SG wrote the manuscript text. SG, JL, TW, and YS prepared figures and collected samples. YL and WY analyzed data. HH and SG designed the experiment. HH and KZ revised the manuscript. All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.