Andrographolide reduces cognitive impairment in young and mature AßPPswe/PS-1 mice.

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disorder in which the amyloid-ß (Aß) oligomers are a key factor in synaptic impairment and in spatial memory decline associated with neuronal dysfunction. This impairment includes synaptic failure associated with the loss of synaptic proteins that contribute to AD progression. Interestingly, the use of natural compounds is an emergent conceptual strategy in the search for drugs with therapeutic potentials for treating neurodegenerative disorders. In the present study, we report that andrographolide (ANDRO), which is a labdane diterpene extracted from Andrographis paniculata, increases slope of field excitatory postsynaptic potentials (fEPSP) in the CA1 region of hippocampal slices and inhibits long-term depression (LTD), protecting the long-term potentiation (LTP) against the damage induced by Aß oligomers in vitro, most likely by inhibiting glycogen synthase kinase-3ß (GSK-3ß). Additionally, ANDRO prevents changes in neuropathology in two different age groups (7- and 12-month-old mice) of an AßPPswe/PS-1 Alzheimer's model. ANDRO reduces the Aß levels, changing the ontogeny of amyloid plaques in hippocampi and cortices in 7-month-old mice, and reduces tau phosphorylation around the Aß oligomeric species in both age groups. Additionally, we observed that ANDRO recovers spatial memory functions that correlate with protecting synaptic plasticity and synaptic proteins in two different age groups. Our results suggest that ANDRO could be used in a potential preventive therapy during AD progression.