Abstract
Alzheimer’s disease (AD) is the most common form of dementia and has no cure. Therapeutic strategies focusing on the reduction of oxidative stress, modulation of amyloid-beta (Aβ) toxicity and inhibition of tau protein hyperphosphorylation are warranted to avoid the development and progression of AD. The aim of this study was to screen the crude extracts (CEs) and ethyl-acetate fractions (EAFs) of Guazuma ulmifolia, Limonium brasiliense, Paullinia cupana, Poincianella pluviosa, Stryphnodendron adstringens and Trichilia catigua using preliminary in vitro bioassays (acetylcholinesterase inhibition, antioxidant activity and total polyphenol content) to select extracts/fractions and assess their protective effects against Aβ25–35 toxicity in SH-SY5Y cells. The effect of the EAF of S. adstringens on mitochondrial membrane potential, lipid peroxidation, superoxide production and mRNA expression of 10 genes related to AD was also evaluated and the electropherogram fingerprints of EAFs were established by capillary electrophoresis. Chemometric tools were used to correlate the in vitro activities of the samples with their potential to be evaluated against AD and to divide extracts/fractions into four clusters. Pretreatment with the EAFs grouped in cluster 1 (S. adstringens, P. pluviosa and L. brasiliense) protected SH-SY5Y cells from Aβ25-35-induced toxicity. The EAF of S. adstringens at 15.62 μg/mL was able completely to inhibit the mitochondrial depolarization (69%), superoxide production (49%) and Aβ25-35-induced lipid peroxidation (35%). With respect to mRNA expression, the EAF of S. adstringens also prevented the MAPT mRNA overexpression (expression ratio of 2.387x) induced by Aβ25–35, which may be related to tau protein hyperphosphorylation. This is the first time that the neuroprotective effects of these fractions have been demonstrated and that the electropherogram fingerprints for the EAFs of G. ulmifolia, L. brasiliense, P. cupana, P. pluviosa and S. adstringens have been established. The study expands knowledge of the in vitro protective effects and quality control of the evaluated fractions.
Highlights
Ongoing advances and developments in modern medicine and science have increased life expectancy, exponentially increasing the prevalence of senile disorders like dementia [1,2]
Our results suggest that the ethyl-acetate fractions (EAFs) of S. adstringens may protect SH-SY5Y cells by inhibiting microtubule-associated protein tau (MAPT) gene overexpression, which is related to the deposition of intra-neuronal neurofibrillary tangles, leading to oxidative stress, cell injury and neurodegeneration [44]
The present study provides information concerning the in vitro protective effects of G. ulmifolia, L. brasiliense, P. cupana, P. pluviosa, S. adstringens and T. catigua against neurodegenerative disease, Alzheimer’s disease (AD)
Summary
Ongoing advances and developments in modern medicine and science have increased life expectancy, exponentially increasing the prevalence of senile disorders like dementia [1,2]. Alzheimer’s disease (AD) is the most common form of dementia and is characterized by the progressive loss of memory, language skills and cognitive ability, leading to death [4,5,6,7]. AD is characterized by excessive deposition of extraneuronal amyloid-beta (Aβ) peptide plaques, intracellular neurofibrillary tangles, hyperphosphorylation of tau protein and neuronal cell death. Abnormal Aβ aggregation and the formation of reactive oxygen species (ROS) due to oxidative stress are the main factors responsible for the development and progression of AD [4,5,6,7,8,9,10,11,12,13]
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