Multi-Target Antioxidant Potential of Tricin Against Parkinson's Disease- Linked Oxidative Stress

Oxidative stress (OS) is a key factor in the degeneration of dopaminergic neurons in Parkinson's disease (PD). It is closely associated with mitochondrial dysfunction, overproduction of reactive oxygen species (ROS), neuroinflammation, and excitotoxicity mediated by nitric oxide (NO). These mechanisms underscore OS as a crucial therapeutic target. This study investigated the molecular interaction of tricin with OS-related targets and validated its antioxidant potential.

Nine protein targets were retrieved from RCSB-PDB, including Peroxisome Proliferator- Activated Receptor Gamma (PPAR-γ), Orphan Nuclear Receptor-Related 1 (NURR1), Lipoprotein- Associated Phospholipase A2 (Lp-PLA2), AKT1, Interleukin-6 (IL-6), Vascular Endothelial Growth Factor (VEGF), Adenosine A2A Receptor (A2AR), Monoamine Oxidase B (MAO-B), and Catechol- O-Methyl-Transferase (COMT). Molecular docking simulations were conducted to assess binding affinities, and in vitro assays confirmed antioxidant activity against free radicals.

Tricin showed effective interactions with all nine targets. It exhibited potent interactions with PPAR-γ, Lp-PLA2, VEGF and COMT compared to their native ligands, with binding energies of -7.3, -8.1, -7.3, and -7.6 kcal/mol, respectively. Additionally, it displayed significant binding affinities for MAO-B, NURR1, AKT1, IL-6, and A2AR, with binding energies of -8.9, -7.1, -5.9, -6.7, and -7.7 kcal/mol, respectively. In vitro assays confirmed concentration-dependent scavenging, with effective inhibitory concentrations against 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydrogen peroxide (H₂O₂).

These findings suggest that tricin may act as a multitarget antioxidant and modulator of OS-related pathways in PD.

The outcomes suggest that tricin could exert neuroprotective effects by inhibiting and scavenging OS and possibly acting on multiple PD-related targets.