Anshen Decoction Improves Synaptic Plasticity and Memory in Insomnia Rats by Regulating Hippocampal Mitochondrial Dysfunction via the AMPK/PGC-1α Pathway

INTRODUCTION: This study investigated the effects of Anshen Decoction (ASD) on heart-kidney disharmony insomnia, focusing on the AMPK/PGC-1α pathway. METHODS: ASD components were analyzed via HPLC. A rat model of heart-kidney disharmony insomnia was established using compound stressors and p-chlorophenylalanine (PCPA). After intervention with ASD, Estazolam, or Wuling capsule (WL), behavioral tests were conducted. Serum levels of stress hormones-Corticotropin-Releasing Hormone (CRH), Adrenocorticotropic Hormone (ACTH), and Cortisol (CORT) were measured. Hippocampal ATP content and mitochondrial respiratory chain complexes III/IV (COX-III/COX-IV) activity were evaluated. HE and JC-1 staining detected histopathology and mitochondrial membrane potential (MMP). Synaptic plasticity proteins (GAP-43, PSD-95, SynI) and AMPK/PGC-1α pathway components were analyzed via Western blot and IHC. RESULTS: Following ASD treatment, the learning and memory capabilities of model rats were significantly enhanced, anxiety and tension were alleviated, hippocampal pathological damage was mitigated, and serum levels of CRH, ACTH, and CORT were reduced. These findings were consistent with those observed in the two positive control groups treated with Estazolam and WL. Moreover, ASD treatment upregulated the levels of GAP-43, PSD-95, SynI, ATP, COX-III, and COX-IV in the hippocampal tissue of model rats, increased MMP levels, and elevated the p- AMPKα /AMPKα protein ratio as well as the expression levels of PGC-1α, NRF-1, and TFAM proteins. CONCLUSION: ASD can ameliorate learning and memory impairments in rats with heart-kidney disharmony insomnia. This effect may be attributed to the activation of the AMPK/PGC-1α axis, which inhibits mitochondrial dysfunction in the hippocampus and enhances synaptic plasticity.