Fucoxanthin Prevents Long-Term Administration l-DOPA-Induced Neurotoxicity through the ERK/JNK-c-Jun System in 6-OHDA-Lesioned Mice and PC12 Cells

Abstract

As the most abundant marine carotenoid extracted from seaweeds, fucoxanthin is considered to have neuroprotective activity via its excellent antioxidant properties. Oxidative stress is regarded as an important starting factor for neuronal cell loss and necrosis, is one of the causes of Parkinson’s disease (PD), and is considered to be the cause of adverse reactions caused by the current PD commonly used treatment drug levodopa (l-DA). Supplementation with antioxidants early in PD can effectively prevent neurodegeneration and inhibit apoptosis in dopaminergic neurons. At present, the effect of fucoxanthin in improving the adverse effects triggered by long-term l-DA administration in PD patients is unclear. In the present study, we found that fucoxanthin can reduce cytotoxicity and suppress the high concentration of l-DA (200 μM)-mediated cell apoptosis in the 6-OHDA-induced PC12 cells through improving the reduction in mitochondrial membrane potential, suppressing ROS over-expression, and inhibiting active of ERK/JNK-c-Jun system and expression of caspase-3 protein. These results were demonstrated by PD mice with long-term administration of l-DA showing enhanced motor ability after intervention with fucoxanthin. Our data indicate that fucoxanthin may prove useful in the treatment of PD patients with long-term l-DA administration.

Role of Carotenoids in Parkinson’s Diseases

“…Additionally, in 6-OHDA-induced PC12 cells, fucoxanthin also upregulated the expression of Keap1 downstream antioxidant enzymes in a dose-dependent manner, including nicotinamide heme oxygenase-1 (HO-1), glutamate-cysteine ligase modification subunit (GCLM), and glutamatecysteine ligase catalytic subunit (GCLC) [129]. Furthermore, fucoxanthin can prevent neurotoxicity and suppress the high concentration of levodopa (L-DOPA)induced cell apoptosis in the 6-OHDA-induced PC12 cells by improving the reduction in mitochondrial membrane potential, suppressing ROS expression, and inhibiting activation of ERK/JNK-c-Jun pathway and expression of cleaved caspase-3 [130].…”

Marine-Derived Components: Can They Be a Potential Therapeutic Approach to Parkinson’s Disease?

“…Liu and coworkers (2022) [ 129 ] reported the neuroprotective effects of fucoxanthin ( 24 ) ( Figure 8 ) isolated from brown seaweeds on the 6-OHDA-lesioned mice model of PD. The authors observed that long-term administration of L-dopa (30 mg/kg) produced neurotoxicity through Caspase-3 and c-Jun expression mediated by the ERK/JNK system; however, with fucoxanthin treatment, a decrease in ERK1/2, JNK1/2, c-Jun phosphorylation, and Caspase-3 was verified, improving the exercise ability of PD mice.…”

Molecular and Cellular Interactions in Pathogenesis of Sporadic Parkinson Disease

“…Moreover, L-DOPA does not counteract non-motor symptoms, which sometimes lead to the same disability as motor ones [ 313 ]. Moreover, high concentrations of L-DOPA as well as DA may induce excessive ROS production and oxidative stress, which can be reduced by dietary supplements like flavonoids and carotenoids [ 314 , 315 ].…”