Cornus mas L. Extracts Exhibit Neuroprotective Properties, Further Enhanced by Metal-Bound Energy-Linked Organic Substrates

Neurodegenerative diseases have been increasingly plaguing the global population, with attempts to understand their etiopathogenesis and pursue therapeutics being at the forefront of multidisciplinary efforts. To that end, research was launched in our lab, based on natural products and bioessential metal ion complex forms to peruse their antioxidant and neuroprotective potential at the cellular level. To that end, the bioactivity profile of optimized <i>Cornus mas</i> L. extracts and supplemented mixtures thereof with soluble-bioavailable well-characterized hybrid materials, Zn(II)-Cit and V(IV)-Cit, was investigated. In vitro experiments on sensitive brain tissue cell lines (N2a58, SH-SY5Y) showed that the extracts and the metal complexes were atoxic (morphology, proliferation, chemotacticity) in a concentration-dependent manner. Subsequently, the antioxidant potential of all materials was examined, with H₂O₂ as the oxidizing agent, thereby revealing through viability and reactive oxygen species (ROS) visualization significant antioxidant activity, while specific genes (<i>NFE2L2</i>, <i>Hmox1</i>, <i>GCLM</i>) were crucial in divulging mechanistic aspects of the antioxidation. Concurrently, the anti-inflammatory activity was evaluated through gene expression (<i>TNF-a</i>, <i>IL-6</i>), with Zn(II) bioavailability projecting intracellular levels linked to the observed sustainable activity. The collective bioactivity profile of the extracts and Zn(II)-Cit reveals significant neuroprotective properties, thereby meriting development of new naturally-based neutraceuticals that proactively avert neuropathological aberrations.