The bioactive compounds from elderberry to modulate mitochondrial dysfunctions underlying Alzheimer's disease
Dina Neves1,, , João Bernardo1, Patrícia Valentão1, Maria C. Oliveira2, David M. Pereira1, Paula B. Andrade1, Romeu A. Videira1
1 REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, N° 228, 4050-213 Porto, Portugal
2 Centro de Química de Vila Real (CQ-VR), Departamento de Química; Escola de Ciências da Vida e do Ambiente, Universidade de Trás-os-Montes e Alto Douro (UTAD), P.O. Box 1013, 5001-801 Vila Real, Portugal

Aim: The specific objective of this work is to establish a correlation between the physical-chemical properties of the aqueous extract of elderberry (Sambucus nigra L.) and its ability to tune the cell redox state and to overcome mitochondrial dysfunctions, which are pathological events with high relevance in Alzheimer's disease (AD).

Introduction: Currently, there is no effective medicine to prevent or delay the progressive brain degeneration underlying cognitive decline and dementia that characterize AD. Previous works support the idea that the loss of mitochondrial functionality, connected with the decline of complex I activity, is able to promote AD phenotype through the activation of multiple pathophysiological pathways, including oxidative stress, neuroinflammation, and also tau and amyloid-beta pathologies. Thus, multi-targeted approaches supported by mixtures of natural bioactive compounds should reveal more effectiveness than classical therapeutics for AD.

Methods: The polyphenolic profile of elderberry extract and of anthocyanin-enriched fraction was evaluated by HPLC-DAD, the optical properties by UV–vis and fluorescence spectroscopy and the redox behavior by cyclic voltammetry. Antioxidant properties were assessed in cell-free assays while the ability the elderberry extract to modulate the mitochondrial redox chain was evaluated in rat brain mitochondria.

Results: HPLC analyses showed that elderberry extract is a mixture of chemical compounds, particularly rich in anthocyanins. It exhibits intrinsic fluorescence properties with potential for bioimaging, reversible redox behavior and ability to scavenge DPPH, nitric oxide and superoxide radicals. The antioxidant, optical and redox properties of elderberry extract are strongly correlated to their content in anthocyanins. Bioenergetic studies show that elderberry extract has ability to promote the oxidation of NADH in aqueous phase and deliver electrons to ubiquinone or complex III in the inner-mitochondrial membrane, overcoming the complex I inhibition promoted by rotenone.

Conclusion: Elderberry anthocyanins have potential to be used in mitochondria-targeted formulations to modulate the pathophysiological changes underlying AD from their early stages.

Acknowledgements: This work received financial support from National Funds (FCT/MEC) through project UID/QUI/50006/2013, co-financed by FEDER through COMPETE, under the Partnership Agreement PT2020, and from NORTE 2020, under the PORTUGAL 2020 Partnership Agreement, through ERDF (NORTE-01-0145-FEDER-000024).

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