Extract from Hancornia speciosa leaves improves behavioral pathological changes induced by amyloid-β in mice

Introduction: Alzheimer’s Disease (AD) is a neurodegenerative disorder which leads to memory loss and dementia. In spite of affecting a large proportion of elderly people, and the advances on the comprehension of its pathophysiology, presently there is no therapeutic approach to prevent AD progress. Neuronal death and neuroinflammation are associated with the pathology development. Moreover, clinical and epidemiological evidences have shown that hypertension is a risk factor for the development of AD. The available pharmacological therapy is based on one-drug-one molecule strategy that is not efficient to treat AD. Natural products from plants represent a promising source of bioactive compounds for treating AD. In the last years, our research group has been studying some plants from the Brazilian savanna (cerrado) with antihypertensive and anti-inflammatory effects. One of the most promising species identified so far was Hancornia speciosa, a plant vulgarly known as “mangabeira”, traditionally used to treat diabetes, hypertension, among other diseases. We have demonstrated the potential antihypertensive effect of an extract from H. speciosa leaves by in vitro inhibition of angiotensin I-converting enzyme, and its vasodilator effect on rat aortic and mesenteric preparations. This activity was ascribed to polyphenols and cyclitols like L-(+)-bornesitol. Epidemiological data indicate that patients treated with anti-hypertensive drugs are less prone to develop AD. Therefore, this work aimed to investigate the effect of an acetone/water (7:3) extract from H. speciosa leaves (HFP1) in a murine model of AD induced by amyloid-β peptide. Methods: All experiments were performed in accordance with Institutional Ethics Committee (Protocol CEUA/UFMG 297/2018). The dried leaves of H. speciosa were percolated with acetone/water (7:3) and the solvent was removed under reduced pressure to afford the extract HFP1. The total proanthocyanidins content in HFP1 was quantified by UV-Vis spectrophotometry. Male C57Bl/6 mice were submitted to stereotactic surgery (-1.5 mm medial-lateral, -2.3 mm dorsal-ventral and -1.9 mm rostral-caudal relative to bregma) to receive an intra-hippocampal unilateral injection of 400 pmol of amyloid-β 1-42 in 0.5 µl of PBS. After 24 hours, the animals were treated daily with HFP1 (10, 30 or 100 mg/Kg) or the vehicle, for 7 days, and then submitted to object recognition task. Six groups were used: A) PBS + vehicle, B) PBS + HFP1 30 mg/Kg, C) amyloid-β + vehicle, D) amyloid-β + HFP1 10 mg/Kg, E) amyloid-β + HFP1 30 mg/Kg and F) amyloid-β + HFP1 100 mg/Kg; n = 8. After the treatment, the animals were submitted to thoracotomy and intracardiac perfusion and then were decapitated. Data were analyzed by one-way ANOVA followed by Bonferoni post-hoc test and values were expressed as mean ± SD. The level of statistical significance was set at a p value less than 0.05. Results: Injection of amyloid-β induced memory impairment as demonstrated by the object recognition task (50.1 ± 7.2% for group C in comparison to 73.3 ± 8.5 % obtained for PBS group A), which was significantly prevented by treatment with HFP1 either at 30 mg/Kg (68.6 ± 14.2 %) or 100 mg/Kg (78.4 ± 7.0%). The content of total proanthocyanidins in HFP1 was 40.4 ± 2.0% w/w. Conclusions: Amyloid-β induces cognitive changes in mice, which can be prevented by oral treatment with HPF1 at 30 mg/Kg or 100 mg/Kg. The extract has a high content of proanthocyanidins that might be related to its biological activity. The chemical characterization of the extract is in course and its mechanism of action will be evaluated in the future. Acknowledgments: CAPES for a master fellowship (WOCJ) and CNPq for the financial support (grant number 434133/2018-3).