Isoquercetin mitigates neuroinflammation and oxidative stress by targeting the NF-κB pathway

Parkinson's disease (PD) manifests as hypokinetic movement disorder because dopamine reduction occurs within midbrain regions, along with striatal dopaminergic neuron destruction. Adult zebrafish, well a well-characterized dopaminergic system, has led to an increase in their utilization in PD research. Adult zebrafish are frequently made to exhibit Parkinsonism using neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), one of the toxin-based models. Therefore, in the present study, adult zebrafish were utilized to explore the neuroprotective effect of Isoquercetin (ISO) against oxidative stress and neuroinflammation by the MPTP-induced model of PD by targeting the pathway. So, three doses of ISO i.e.12.5, 25, and 50 mg/kg, were used against MPTP (20 g/kg) for 7 days. Behavioral symptoms like motility and anxiety were improved using the novel diving tank test and the open field test. Biochemical analysis revealed that zebrafish treated with ISO in MPTP exposed zebrafish enhanced SOD, Catalase, and GSH activity and decreased MDA activity, inhibited proinflammatory mediators viz. IL-6, TNF-α, and IL-1β. During the histopathological study, ISO gradually reduced the number of pyknotic neurons in the midbrain in MPTP-treated zebrafish. The docking analysis of ISO into the binding pocket of NF-κB (PDB id: 1LE7) showed that the molecule fitted well into the protein binding pocket and showed favorable results. According to an IHC study, ISO decreased the expression of NF-κB, which results in a decrease in neuroinflammation. The neuroprotective effect of ISO in MPTP-induced PD in zebrafish is attributed by modulating by NF-κB pathway.