Nervonic acid suppresses MPTP-induced Parkinson's disease in an adult zebrafish model by regulating the MAPK/NF-κB signaling pathway, inflammation, apoptosis, and oxidative stress

Being a chronic inflammatory condition, Parkinson's disease (PD) can lead to brain damage. Nervonic acid is one of the most promising bioactive fatty acids, which is believed to be beneficial for the improvement of brain disorders. This study explored the neuroprotective capabilities of nervonic acid on the brain in an adult zebrafish PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Initially, the physiological behaviors of zebrafish with PD following nervonic acid treatment were assessed. Subsequently, molecular level transcriptome analysis was conducted to investigate its protective mechanism. Finally, the mechanisms of target pathways were validated through real-time PCR, immunohistochemistry, and Western blotting. The results showed that nervonic acid improved the locomotor capabilities of zebrafish with PD at the behavioral level. At the molecular level, it is likely that nervonic acid exerted its effects by suppressing inflammatory signaling pathways, such as mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), as well as addressing oxidative stress response and apoptosis. By inhibiting the expression of toll-like receptor 4 (TLR4), jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38α MAPK, NF-κB p65, and nuclear factor kappa B α (IκBα), nervonic acid disrupted the MAPK/NF-κB signaling pathway. Furthermore, it exhibited anti-inflammatory effects by reducing the expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Additionally, nervonic acid increased the levels of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) while decreasing malondialdehyde (MDA) content, demonstrating its antioxidative properties. Moreover, the acid upregulated the expression of B-cell lymphoma 2 (Bcl-2) and downregulated the levels of Bcl-2-associated X protein (Bax), Caspase-3, and Caspase-9, indicating its protective role against apoptosis. These findings suggest that nervonic acid mitigates MPTP-induced brain damage through its antioxidative, anti-inflammatory, and anti-apoptotic properties. This positions it as a promising candidate for a natural neuroprotective agent.