Tianqi Yizhi Granule alleviates cognitive dysfunction and neurodegeneration in SAMP8 mice via the PKC/ERK pathway

Background: Given the lack of satisfactory clinical treatments for Alzheimer's disease (AD), a neurodegenerative condition detrimental to health, developing alternative therapies is critical. Tianqi Yizhi Granule (TQYZ) is a preparation used to treat AD based on traditional Chinese medicine theory, the latent mechanisms of which await elucidation.

Purpose: This study sought to investigate the neuroprotective properties of TQYZ while exploring its potential therapeutic mechanisms using network pharmacology analyses and experimental validation.

Methods: Network pharmacology analyses were performed. Cognitive and neurodegenerative alterations were evaluated through behavioral tests and histological staining. For in vivo and in vitro experiments, short hairpin RNA sequences were transfected via adeno-associated virus vectors to verify the predicted mechanism.

Results: A total of 159 potential therapeutic targets of TQYZ overlapped with AD-related targets. In senescence-accelerated mouse prone 8 (SAMP8) mice, treatment with TQYZ significantly improved cognitive function, ameliorated neuronal damage and Apoptosis, and upregulated the protein expression of PKC/ERK pathway members. TQYZ maintained the mitochondrial membrane potential, reduced the generation of Reactive Oxygen Species, and inhibited neuronal Apoptosis in Aβ_25-35-induced HT22 cells. However, these neuroprotective effects were notably reduced in shRNA PRKCB-transfected HT22 cells and SAMP8 mice.

Conclusions: TQYZ mitigates the pathological degeneration process and cognitive impairment in SAMP8 mice and suppresses mitochondrial dysfunction and Apoptosis in HT22 cells treated with Aβ_25-35. Its neuroprotective mechanism is linked to PKC/ERK pathway activation. This study highlights a promising strategy for AD therapy.

Alzheimer's disease; Network pharmacology; Neuronal apoptosis; PKC/ERK; Traditional Chinese medicine.