Beneficial Effects of the Herbal Medicine Zuo Gui Wan in a Mice Model of Alzheimer's Disease via Drp1-Mediated Inhibition of Mitochondrial Fission and Activation of AMPK/PGC-1α-regulated Mitochondrial Bioenergetics
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE
Zuo Gui Wan (ZGW) is a well-known traditional Chinese medicine decoction used for approximately 400 years to treat age-related degenerative conditions, including cognitive impairment in older adults, osteoporosis, and general aging. However, the mechanism of action for ZGW remains unclear.
AIMS OF THE STUDY
This study aims to investigate the efficacy of ZGW in improving cognitive function in Alzheimer's disease (AD) animal models and to explore the underlying mechanisms, presenting a novel perspective in the field.
MATERIALS AND METHODS
Six-month-old male APP/PS1 mice were divided into three groups that received either metformin (200 mg/kg daily) or ZGW (6 and 12 g/kg daily). High-performance liquid chromatography was conducted for ZGW's quality control. Cognitive function was assessed using the Morris water maze test. Neuronal loss, synaptic plasticity, and β-amyloid (Aβ) deposition were evaluated through Western blot or immunofluorescence staining. The underlying molecular mechanisms were investigated using ELISA, Western blot, qRT-PCR, co-immunoprecipitation assay, ATP assay, and cytochrome c oxidase assay.
RESULTS
ZGW, administered in both low and high doses, significantly enhanced cognitive performance, notably decreased neuronal loss and Aβ deposition, and reduced levels of Aβ1-40/42. It also inhibited excessive mitochondrial division primarily by suppressing phosphorylated Drp1, especially at high doses of ZGW. Co-immunoprecipitation…
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