Aconiti lateralis Radix Praeparata inhibits Alzheimer’s disease by regulating the complex regulation network with the core of GRIN1 and MAPK1

Abstract

Context

Current medicine for Alzheimer’s disease (AD) cannot effectively reverse or block nerve injury. Traditional Chinese Medicine practice and research imply Aconiti lateralis Radix Praeparata (Fuzi) may meet this goal.

Objective

Analysing the anti-AD effect of Fuzi and its potential molecular mechanism.

Materials and methods

AD model cells were treated with Fuzi in 0-300 mg/mL for 24 h in 37 °C. The cell viability (CV) and length of cell projections (LCP) for each group were observed, analysed, and standardised using control as a baseline (CV_s and LCP_s). The Fuzi and AD relevant genes were identified basing on databases, and the molecular mechanism of Fuzi anti-AD was predicted by network analysis.

Results

Experiment results showed that Fuzi in 0.4 mg/mL boosted LCP (LCP_s = 1.2533, p ≤ 0.05), and in 1.6–100 mg/mL increased CV (CV_s from 1.1673 to 1.3321, p ≤ 0.05). Bioinformatics analysis found 17 Fuzi target genes (relevant scores ≥ 20), showing strong AD relevant signals (RMS_p ≤ 0.05, related scores ≥ 5), enriched in the pathways regulating axon growth, synaptic plasticity, cell survival, proliferation, apoptosis, and death (p ≤ 0.05). Especially, GRIN1 and MAPK1 interacted with APP protein and located in the key point of the “Alzheimer’s disease” pathway.

Discussion and conclusions

These results suggest that Fuzi may have therapeutic and prevention potential in AD, and GRIN1 and MAPK1 may be the core of the pathways of the Fuzi anti-AD process. Fuzi should be studied more extensively, especially for the prevention of AD.

Keywords:

• Fuzi
• therapy
• APP cells
• aminophenol

Acknowledgement

We thank Prof. Jia Liu and Prof. Tinghua Wang for kindly providing the APP cells.

Author contributions

Y-T.W and H-X.Z performed experiment and analysis in the research and prepared figures and tables of this paper. J.W, M.Y and Q-Q.Z analysed experiment data and wrote the main manuscript and prepared figures and tables of this paper. S.Y, D-Y.Y, L-L.S, and L-H.Z gave some advice on data analysis and helped to revise the draft of the manuscript writing. L-M.W, H-X.W, and X.C designed the research, analysed the data and revise the draft of the manuscript writing.

Disclosure statement

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article [and/or] its Supplementary materials.

Additional information

Funding

This research is supported by The National Natural Science Foundation of China [81860255, 81760869], Innovative experimental project for college students of Kunming Medicine University. Cao Xue is supported by the Hundred-Talent Program of Kunming Medical University.