Preparation and Neuroprotective Activity of Glucuronomannan Oligosaccharides in an MPTP-Induced Parkinson’s Model

Abstract

Parkinson’s disease (PD), characterized by dopaminergic neuron degeneration in the substantia nigra and dopamine depletion in the striatum, affects up to 1% of the global population over 50 years of age. Our previous study found that a heteropolysaccharide from Saccharina japonica exhibits neuroprotective effects through antioxidative stress. In view of its high molecular weight and complex structure, we degraded the polysaccharide and subsequently obtained four oligosaccharides. In this study, we aimed to further detect the neuroprotective mechanism of the oligosaccharides. We applied MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to induce PD, and glucuronomannan oligosaccharides (GMn) was subsequently administered. Results showed that GMn ameliorated behavioral deficits in Parkinsonism mice. Furthermore, we observed that glucuronomannan oligosaccharides contributed to down-regulating the apoptotic signaling pathway through enhancing the expression of tyrosine hydroxylase (TH) in dopaminergic neurons. These results suggest that glucuronomannan oligosaccharides protect dopaminergic neurons from apoptosis in PD mice.

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

“…We applied Western blot and immunofluorescence to analyze TH in both striatum and substantia nigra. As shown in Figure 5 A–D, MPTP induced a reduction in the protein expression of TH and a decrease in TH-positive neurons in the striatum; however, treatment with GM2 markedly prevented TH loss, consistent with previous reports [ 23 ]. Similar results were observed in the substantia nigra, showing that GM2 protected dopaminergic neurons from MPTP-induced apoptosis through enhancement of TH levels ( Figure 5 E–H).…”

“…Our previous study reported that the glucuronomannan oligosaccharide GM2 from Saccharina japonica could ameliorate behavioral deficits and increased the protein level of TH in the striatum of Parkinsonism mice [ 23 ]. TH, the rate-limiting enzyme in the synthesis of DA, is often used as a marker for the integrity of dopaminergic neurons [ 42 , 43 ].…”

“…For the preparation of GM2, please refer to a previous study ( Figure 8 ) (see the Supplementary Materials ) [ 23 ].…”

“…Considering its high molecular weight and complex structure, we hydrolyzed the polysaccharide, obtaining three glucuronomannan oligosaccharides (GMn; GM1, GM2, GM3) and applied the oligosaccharides in a MPTP-induced Parkinson’s model. The results revealed that GMn ameliorated behavioral deficits in Parkinsonism mice and downregulated the apoptotic signaling pathway, especially with GM2 showing a more effective role in neuroprotection [ 23 ]. However, how did GM2 play the neuroprotective role?…”

Neuroprotective Effects of Oligosaccharides From Periplaneta Americana on Parkinson’s Disease Models In Vitro and In Vivo

“…Batryticatus Bombyx have been reported to protect DAergic neurons against MPTP-induced neurotoxicity by alleviating oxidative damage and improving behavioral impairments in PD model mice ( Lim et al, 2019 ). Up to now, a series of studies demonstrated that polysaccharides or oligosaccharides with bioactivities from plants, animals, and fungi exerted promising therapeutic effects for preventing neurodegenerative disorders mainly by the microbiota-gut-brain axis in MPTP-induced PD model, such as Astragalus polysaccharides ( Li et al, 2016 ; Souza et al, 2017 ), fucoidan ( Kim et al, 2017 ), and oligomannurarate 971 ( Liu et al, 2020a ). Growing evidence implicated that dysbiosis in the abundance and composition of gut microbiota could affect both the central nervous system (CNS) and the enteric nervous system (ENS) ( Liu et al, 2022 ).…”