Evaluation of the neuroprotective potential of violacein in ex vivo and in vivo models of Parkinson’s disease

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder lacking disease-modifying therapies. Violacein (Vio), a natural compound from Chromobacterium violaceum, has antioxidant, anti-inflammatory, and neuroprotective properties. This study evaluated its effects in ex vivo and in vivo PD models. Methods: Striatal and hippocampal slices from Wistar rats were exposed to 6-hydroxydopamine (6-OHDA) with or without Vio. Cell viability, SUMO-2/3 conjugation, and SENP3 levels were analyzed. In vivo, rats received bilateral intrastriatal 6-OHDA (10 or 20 µg) and Vio (300 nmol/kg, i.p.), followed by behavioral and oxidative stress analyses. Results: Vio prevented 6-OHDA-induced toxicity ex vivo. SUMO-2/3 conjugation decreased in the hippocampus, while SENP3 levels were reduced in both regions. In vivo, Vio partially improved memory, anxiety- and depressive-like behaviors, mainly at the lower 6-OHDA dose. It also increased GSH and reduced MDA and ROS, especially in the prefrontal cortex and hippocampus. Conclusion: Vio showed neuroprotective effects in PD models, mainly by reducing oxidative stress rather than modulating SUMOylation. These findings support its potential as a disease-modifying therapy, particularly in early or moderate PD onset. Funding: Studentships from CAPES (L.Y.Q. and M.S.P.); CNPq (B.J.C.; productivity in research to L.M.S. and H.I.C.; grants 445750/2023-5 and 403204/2024-0); FAPESC (R.S.V.; C.H.W.; grant 2024TR1733.