Avaliação fitoquímica e do potencial neuroprotetor de Hancornia speciosa Gomes em modelo murino de doença de Alzheimer.

Abstract

Alzheimer's disease (AD) is the most common form of dementia and manifests itself through signs such as memory loss, spatial disorientation, progressive loss of cognitive function and intellectual impairment. Senescence and senility are the main risk factors for the development and progression of AD. In addition, epidemiological studies have shown that hypertension is a risk factor for dementias, and strong clinical evidence that the use of antihypertensive drugs by the elderly may be associated with a lower incidence of dementias and a delay in cognitive decline and reduced neuroinflammation. In recent years, our group has demonstrated the potential antihypertensive effect of several plants in the Brazilian Savana like bioma (Cerrado), among which, Hancornia speciosa, popularly known as “mangabeira”, has stood out. For this purpose, male C57 Bl/6 mice, aged between 10 and 12 weeks, were treated for 7 days with acetone:water extract (70:30) from H. speciosa leaves, in doses of 10, 30 and 100 mg/kg, then being submitted to the Object Recognition Task (ORT). Our results showed that the extracts did not induce cognitive changes in animals tested in ORT. In sequence, different animals were submitted to stereotactic surgery for intra-hippocampal injection of Aβ1-42 or PBS and were treated with the same extract and doses, for 7 days. Our results showed that the extract, administered per os, at doses of 30 and 100 mg/kg was able to reverse the cognitive damage induced by Aβ1-42. Then, the aforementioned extract was submitted to the phytochemical study. Preliminary analyzes showed the presence of several secondary metabolites, mainly polyphenolics, such as rutin and proanthocyanidins. The quantification of proanthocyanidins by UV/VIS spectrometry demonstrated a content of ca. 4,5% w/w of these metabolites. The extract was then fractionated by Sephadex LH-20 chromatography column and the fractions obtained were combined by TLC into 3 groups of fractions enriched in proanthocyanidins. The TS2C3 fraction showed less chemical complexity and sufficient amount for further studies and the characterization of its constituents. Major peaks were identified by UPLC-ESI-MS-MS as being dimeric proanthocyanidin hexosides (peaks 1 (Tr = 2.84 min); 2 (Tr = 3.01 min); 3 (Tr = 3.21 min) ; 4 (Tr = 3.30 min)), with molar weight of 740 g/mol, as well as trimeric derivatives (peaks 6 (Tr = 3.53 min) and 7 (Tr = 3.64 min)), with molar weight of 1028 g/mol. Further studies will still be carried out to define the chemical identity of the major constituents of this fraction as well as its neuroprotective potential in an AD model. The histopathological findings after treatment with the extract and the fraction will be also evaluated. Our results shows that the acetone:water extract (70:30) from H. speciosa revert the cognitive deficit induced by Aβ1-42.