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 Aβ
25–35
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 Aβ
25-35
-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 Aβ
25-35
-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 Aβ
25–35
, 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.
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