This study aimed to investigate the potential effects of
Gomisin B, a natural compound known for its inhibition of
CYP3A4, on
cognitive dysfunction in APP/PS1 transgenic mice with
Alzheimer's disease (AD). Additionally, the study explored the combined effects of
Gomisin B and
Osthole (OST). The research involved male wild-type (WT) mice and 7-month-old APP/PS1 transgenic AD mice. The assessment of behavioral changes included the use of the open field test (OFT) and the Morris water maze (MWM). OST levels in brain tissue were quantified using LC-MS/MS, while levels of oxidative stress were measured through an assay kit. Neuronal apoptosis was studied using Nissl staining, RT-qPCR, and immunofluorescence.
Amyloid plaque clearance was assessed using
thioflavine-S (Th-S) staining, RT-qPCR, and ELISA. The results of the study revealed that
Gomisin B led to a significant improvement in
cognitive dysfunction in APP/PS1 mice. Moreover, the simultaneous administration of OST and
Gomisin B demonstrated enhanced
therapeutic effects. These effects were attributed to the inhibition of β-site APP-Cleaving
Enzyme 1 (BACE1) and oxidative stress by
Gomisin B, along with its anti-apoptotic properties. The combined use of OST and
Gomisin B exhibited a synergistic impact, resulting in more pronounced
anti-oxidant and anti-apoptotic effects. In summary, this study pioneers the exploration of
Gomisin B's multifunctional anti-AD properties in APP/PS1 mice. The findings provide a solid groundwork for the development of anti-Alzheimer's drugs based on natural active ingredients.