Fucoidan Protects Dopaminergic Neurons by Enhancing the Mitochondrial Function in a Rotenone-induced Rat Model of Parkinson’s Disease

Abstract

The mitochondrion is susceptible to neurodegenerative disorders such as Parkinson’s disease (PD). Mitochondrial dysfunction has been considered to play an important role in the dopaminergic degeneration in PD. However, there are no effective drugs to protect mitochondria from dysfunction during the disease development. In the present study, fucoidan, a sulfated polysaccharide derived from Laminaria japonica, was investigated and characterized for its protective effect on the dopamine system and mitochondrial function of dopaminergic neurons in a rotenone-induced rat model of PD. We found that chronic treatment with fucoidan significantly reversed the loss of nigral dopaminergic neurons and striatal dopaminergic fibers and the reduction of striatal dopamine levels in PD rats. Fucoidan also alleviated rotenone-induced behavioral deficits. Moreover, the mitochondrial respiratory function as detected by the mitochondrial oxygen consumption and the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and nuclear transcription factor 2 (NRF2) were reduced in the substantia nigra of PD rats, which were markedly reversed by fucoidan. Oxidative products induced by rotenone were significantly reduced by fucoidan. Taken together, these results demonstrate that fucoidan possesses the ability to protect the dopamine system in PD rats. The neuroprotective effect of fucoidan may be mediated via reserving mitochondrial function involving the PGC-1α/NRF2 pathway. This study provides new evidence that fucoidan can be explored in PD therapy.

Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases

“…Major sulfated polysaccharides found in marine algae include fucoidan from brown seaweed, ulvan from green seaweed, and carrageenan from red seaweed. Several studies have reported on the neuroprotective effect of fucoidan in various neurodegeneration models [209][210][211][212][213][214]. Luo et al's study [209] demonstrated that fucoidan, isolated from Laminaria japonica, attenuated MPTP-induced locomotor activity deficits, prevented depletion of striatal dopamine and its metabolite, dihydroxyphenylacetic acid (DOPAC) level, reduced loss of dopaminergic neurons and tyrosine hydroxylase protein expression, and attenuated the increase of lipid peroxidation level and decreases of antioxidant enzyme activities as well as total antioxidant capacity in the substantia nigra pars compacta of MPTPinduced mice.…”

“…In the 6-OHDA rat model of Parkinson's disease, fucoidan from Laminaria japonica also reduced the dopaminergic neuronal loss in the substantia nigra pars compacta and dopaminergic fibers, inhibited the increase of NADPH oxygenase-1 (NOX1), oxidative stress, and microglial activation in the substantia nigra pars compacta, and attenuated motor dysfunction in 6-ODHA-induced rats [210]. In another rat model of Parkinson's disease, fucoidan from Laminaria japonica alleviated Parkinson's disease-like behaviors, reduced nigral dopaminergic neuronal loss and oxidative stress, prevented the reduction on dopamine and its metabolites, and enhanced mitochondrial respiratory function through the peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α)/Nrf2 pathway in rotenone-induced rats [211].…”

Neuroprotective effects of Shende’an tablet in the Parkinson’s disease model

“…However, PGC-1a and Nrf2 coordinate a large part of the enzymatic antioxidant defense system. More and more evidence indicates that PGC-1α/Nrf2 pathway is a promising target for drug discovery against PD [34,37,38]. Recently, Zhang et al reported that fucoidan has the ability to protect the dopamine system in PD rats, which may be mediated by reserving mitochondrial function involving the PGC-1α/Nrf2 pathway [38].…”

Disease Progression-Dependent Expression of CD200R1 and CX3CR1 in Mouse Models of Parkinson’s Disease

“…Using a bright-field Olympic microscope, the boundaries of the SNpc area were traced. The number of TH-immunoreactive cells within the traced area was counted by stereology using Stereo Investigator software (MBF Bioscience), as described previously [27].…”