Glucuronomannan GM2 from Saccharina japonica Enhanced Mitochondrial Function and Autophagy in a Parkinson’s Model

Abstract

Parkinson’s disease (PD), one of the most common neurodegenerative disorders, is caused by dopamine depletion in the striatum and dopaminergic neuron degeneration in the substantia nigra. In our previous study, we hydrolyzed the fucoidan from Saccharina japonica, obtaining three glucuronomannan oligosaccharides (GMn; GM1, GM2, and GM3) and found that GMn ameliorated behavioral deficits in Parkinsonism mice and downregulated the apoptotic signaling pathway, especially with GM2 showing a more effective role in neuroprotection. However, the neuroprotective mechanism is unclear. Therefore, in this study, we aimed to assess the neuroprotective effects of GM2 in vivo and in vitro. We applied GM2 in 1-methyl-4-phenylpyridinium (MPP+)-treated PC12 cells, and the results showed that GM2 markedly improved the cell viability and mitochondrial membrane potential, inhibited MPP+-induced apoptosis, and enhanced autophagy. Furthermore, GM2 contributed to reducing the loss of dopaminergic neurons in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice through enhancing autophagy. These data indicate that a possible protection of mitochondria and upregulation of autophagy might underlie the observed neuroprotective effects, suggesting that GM2 has potential as a promising multifunctional lead disease-modifying therapy for PD. These findings might pave the way for additional treatment strategies utilizing carbohydrate drugs in PD.

Chitosan oligosaccharides exert neuroprotective effectsviamodulating the PI3K/Akt/Bcl-2 pathway in a Parkinsonian model

“…48 Many studies confirmed that the expression of TH was reduced in PD patients, and the increased expression of TH protein could significantly alleviate PD. 10,13,14 In this research, we characterized TH expression in the striatum by WB (Fig. 5A and C).…”

“…protein could significantly alleviate PD. 10,13,14 In this research, we characterized TH expression in the striatum by WB (Fig. 5A and C).…”

“…10,12 Natural products have been regarded as relatively effective and safe agents, and polysaccharides from marine organisms have received high attention for neuroprotection recently. 14,15 Chitin is the second-largest biological resource after cellulose, and chitosan oligosaccharide (COS) is a hydrolysate of chitosan from shrimp and crab shells, with a molecular weight (M w ) less than 3.9 kDa, composed of N-acetyl-D-glucosamine and β-1,4-linked D-glucosamine. 16 COS has gained consider-able attention presently, due to its fine solubility (water), low toxicity, and easy degradability.…”

Marine Pharmacology in 2019‐2021: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti‐Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…It also demonstrated lesser human dopamine D3 receptor agonist activity, potentially as a novel therapeutic for PD management [142]. [143]. Paudel and colleagues additionally evaluated the bromophenol (54), as a mixed-type inhibitor of AChE, a competitive inhibitor of butyrylcholinesterase (BChE), as well as noncompetitive inhibition of BACE1 in vitro, indicating therapeutic potential for AD management [144].…”