Behavioral, pathological, electrophysiological, and transcriptomic analyses of neuroprotective effects of Huishen Granules on Alzheimer's Disease mice

Abstract

Introduction

Alzheimer’s disease (AD), a prevalent neurodegenerative disorder, still lacks effective therapeutic interventions. Huishen Granules (HSG) as a traditional Chinese medicine prescription has shown therapeutic potential in AD, yet its mechanism remains unclear.

Methods

In this study, the neuroprotective effects of HSG were evaluated in 5 × FAD mice, a well-established AD model. Mice were randomly assigned to three groups: wild-type control (WT), AD model (AD) group, and HSG-treated groups. Cognitive and anxiety-like behaviors were evaluated using the Morris water maze, open-field test, novel object recognition test, and elevated plus maze. Hippocampal synaptic plasticity was assessed via in vivo electrophysiological recordings. Toxicity assessed by hematological tests and histopathology. Whole transcriptome sequencing combined with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified HSG-targeted genes and pathways.

Results

HSG administration improved cognitive performance, synaptic plasticity, and histological appearance in AD mice without toxicity. Transcriptomic analysis of hippocampal tissue identified 178 differentially expressed mRNAs between the WT and AD groups, among which 13 mRNAs showed significant alterations following HSG treatment. These genes primarily regulate energy metabolism, synaptic transmission, and inflammatory responses.

Discussion

Collectively, these findings suggest that HSG mitigates cognitive deficits and neuronal pathology in AD mice by targeting multiple biological pathways, thereby providing a theoretical basis for its potential clinical application in AD therapy.