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Dr. Romeu Videira

Pursuing a proficient elderberry anthocyanin and lipid-based nanoformulation for mitochondria-targeted therapy: the challenge of the degenerative brain diseases

Short Abstract:

The development of therapeutic strategies to modulate mitochondrial function is a great scientific challenge, since deficient activity of the mitochondrial redox chain complexes (e.g., mainly complex I) and abnormal mitochondrial lipidome (e.g., mainly cardiolipin profile) are common pathological hallmarks of many degenerative pathologies, including Parkinson's (PD) and Alzheimer’s (AD) diseases. To address this challenge, we propose an innovative SC-Nanophytosomes formulation built with an elderberry anthocyanin-enriched extract (Sambucus nigra) and the membrane polar lipids obtained from Codium tomentosum. The anthocyanin-enriched extract is dominated by four cyanidin-glycosides with mitochondriotropic compounds and ability to work in mitochondrial inner membrane as electron carriers that oxidize NADH and deliver electrons for complex III, bypassing mitochondrial dysfunctions associated with impaired complex I activity. Algae membrane polar lipids are characterized by 26% of non-phosphorus polar lipids and 74% of phospholipids, containing high abundance of phosphatidylglycerols (cardiolipin precursor) and fatty acids with high ratio of omega3/omega6 PUFA. SC-Nanophytosomes engineered with 600 µM algae membrane polar lipids and 0.5 mg/L of the anthocyanin-enriched extract are nanosized vesicles with a negative surface charge that exhibit stability during storage at 4 ºC.  In vitro assays with SH-SY5Y cells showed that SC-Nanophytosomes have the competence to target mitochondria via caveola-mediated endocytosis, improving the activity of complexes I and II and preserving the mitochondrial membrane potential in the presence of rotenone. Additionally, the oral administration of SC-Nanophytosomes promote positive outcomes in rat with PD-like pathology, suggesting that they have potential to support a mitochondria-targeted therapy for neurodegenerative brain diseases.

 

Acknowledgements: The work was supported through the project UIDB/50006/2020, funded by FCT/MCTES through national funds. Daniela Mendes thanks FCT (Fundação para a Ciência e Tecnologia) and ESF (European Social Fund) through POCH (Programa Operacional Capital Humano) for her PhD grant (SFRH/BD/138206/2018).

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Short CV:

Romeu A. Videira (RV – male; author/co-author of 50 research papers, 4 book chapters and 1 international patent application) was graduated in Biochemistry, University of Coimbra, in 1993, and achieved his Ph.D. degree in 2003, in Biochemistry, University of Coimbra. He assumed duties as teaching assistant (1998-2009) in Polytechnic Institute of Viseu. From July 2009 to 2015, RV was Assistant Investigator in University of Trás-os-Montes e Alto (UTAD). From April 2016 to the present, Romeu Videira is Researcher of LAQV-REQUIMTE, University of Porto (UP), developing his investigation within the Natural Products - chemistry and bioactivity group. Currently he is also Invited Assistant of FFUP.

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