Tripchlorolide improves cognitive deficits by reducing amyloid β and upregulating synapse-related proteins in a transgenic model of Alzheimer's disease

This study investigated effects of tripchloride on Aβ levels, synaptic plasticity, and cognitive function in AD Tg mice. Synaptic plasticity is widely considered to be the cellular foundation for learning and memory in the brain, and changes in the expression of synaptic markers are a reliable predictor of disease progression and cognitive decline. Tripchlorolide (T4), an extract from a traditional Chinese herbal Tripterygium wilfordii Hook F, has been shown to be neuroprotective in animal models of Parkinson’s disease and to improve cognitive deficits in senescence-accelerated mouse P8. In this study, using the 5X FAD mouse model, T4 treatment significantly improved spatial learning and memory, alleviated synaptic ultrastructure degradation, and up-regulated expression of synapse-related proteins. T4 treatment also significantly reduced cerebral Aβ deposits and lowered Aβ levels in brain homogenates. These effects coincided with a reduction in cleavage of β-carboxyl-terminal APP fragments and protein expression of BACE 1. Taken together, these findings identify T4 as a potent negative regulator of brain Aβ levels and show that it significantly ameliorates synaptic degeneration and cognitive deficits in a mouse model of AD.