Sophocarpine Attenuates Cognitive Impairment and Promotes Neurogenesis in a Mouse Model of Alzheimer's Disease.

INTRODUCTION: Alzheimer's disease (AD), which is characterized by abnormal deposition of amyloid-ß (Aß) plaques and impaired neurogenesis and cognition, still lacks an optimally effective therapeutic agent for its management, and mounting evidence has shown that inflammatory processes are implicated in AD. Sophocarpine has been reported to exert inflammation-regulating effects in various diseases. However, whether sophocarpine can exert anti-neuroinflammatory and neuroprotective effects in AD remains unclear. This study investigated whether sophocarpine could ameliorate the pathological features and potential mechanisms in a mouse AD model. METHODS: APP/PS1 mice were treated with sophocarpine for 8 weeks. We quantified the effects of sophocarpine treatment on cognitive performance using a behavioral test. Brain Aß deposits and neurogenesis were evaluated using immunofluorescence staining. We also assessed the morphology and inflammatory changes induced by sophocarpine administration and its expression in the hippocampus. RESULTS: Administration of sophocarpine significantly alleviated cognitive impairment and reduced neural loss. APP/PS1 mice treated with sophocarpine showed reduced Aß plaque deposits and enhanced neurogenesis. Sophocarpine markedly decreased the expression of inflammation markers and inhibited microglial activation. CONCLUSIONS: Sophocarpine could potentially alleviate cognitive impairment and brain damage in APP/PS1 mice with its neuroprotective effects via modulation of the inflammatory pathway.

ß-Sitosterol treatment attenuates cognitive deficits and prevents amyloid plaque deposition in amyloid protein precursor/presenilin 1 mice.

Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia worldwide, and is mainly characterized by aggregated ß-amyloid (Aß). Increasing evidence has shown that plant extracts have the potential to delay AD development. The plant sterol ß-Sitosterol has a potential role in inhibiting the production of platelet Aß, suggesting that it may be useful for AD prevention. In the present study, we aimed to investigate the effect and mechanism of ß-Sitosterol on deficits in learning and memory in amyloid protein precursor/presenilin 1 (APP/PS1) double transgenic mice. APP/PS1 mice were treated with ß-Sitosterol for four weeks, from the age of seven months. Brain Aß metabolism was evaluated using ELISA and Western blotting. We found that ß-Sitosterol treatment can improve spatial learning and recognition memory ability, and reduce plaque load in APP/PS1 mice. ß-Sitosterol treatment helped reverse dendritic spine loss in APP/PS1 mice and reversed the decreased hippocampal neuron miniature excitatory postsynaptic current frequency. Our research helps to explain and support the neuroprotective effect of ß-Sitosterol, which may offer a novel pharmaceutical agent for the treatment of AD. Taken together, these findings suggest that ß-Sitosterol ameliorates memory and learning impairment in APP/PS1 mice and possibly decreases Aß deposition.