Rosmarinic acid and ursolic acid alleviate deficits in cognition, synaptic regulation and adult hippocampal neurogenesis in an Aβ1-42-induced mouse model of Alzheimer's disease

Rosmarinus officinalis, commonly known as rosemary, is a medicinal herb that presents significant biological properties such as antimicrobial, antioxidant, anti-inflammatory, anti-diabetic and anti-depressant activities. Recent findings correlate impaired adult neurogenesis, which is crucial for the maintenance of synaptic plasticity and hippocampal functioning, synaptic regulation with the pathological hallmarks of Alzheimer's disease (AD). These observations call for the need to developing compounds that promote neurogenesis and alleviates deficits in cognition and synaptic regulation. The present study was conducted to determine the proneurogenic effects of R. officinalis and its active compounds (ursolic acid and rosmarinic acid) in comparison to Donepezil in an Aβ1-42-induced mouse model of AD. BALB/c mice were divided into ten groups. Half were injected with Aβ1-42 in the hippocampus through stereotaxic surgery to generate the disease groups. The other half received control injections. Each set of five groups were administered orally with vehicle, an ethanolic extract of R. officinalis, ursolic acid, rosmarinic acid or donepezil. Behavior analysis included the Morris water maze test, the novel object recognition test and the Elevated plus maze. The mice were then sacrificed and the hippocampal tissue was processed for immunohistochemistry and gene expression analysis. The results show a protective effect by rosmarinic acid and ursolic acid in reversing the deficits in spatial and recognition memory as well as changes in anxiety induced by Aβ1-42. The neuronal density and the expression levels of neurogenic (Ki67, NeuN and DCX) and synaptic (Syn I, II, III, Synaptophysin and PSD-95) markers were also normalized upon treatment with rosmarinic and ursolic acid. Our findings indicate the potential of R. officinalis and its active compounds as therapeutic agents against Aβ1-42-induced neurotoxicity in AD.