Protective Effects of Fucoidan on Aβ25–35 and d-Gal-Induced Neurotoxicity in PC12 Cells and d-Gal-Induced Cognitive Dysfunction in Mice

Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disease which contributes to memory loss and cognitive decline in the elderly. Fucoidan, extracted from brown algae, is a complex sulfated polysaccharide and potential bioactive compound. In this study, we investigated whether fucoidan protects PC12 cells from apoptosis induced by a combination of beta-amyloid 25–35 (Aβ25–35) and d-galactose (d-Gal), and improves learning and memory impairment in AD model mice. The results indicated that fucoidan could inhibit the release of cytochrome c from the mitochondria to cytosol and activation of caspases, and increase the expression of apoptosis inhibitor proteins (IAPs), including livin and X-linked IAP (XIAP) in PC12 cells damaged by Aβ25–35 and d-Gal-induction. Fucoidan reversed the decreased activity of acetylcholine (ACh) and choline acetyl transferase (ChAT), as well as the increased activity of acetylcholine esterase (AChE), in AD model mice induced by infusion of d-Gal. Furthermore, fucoidan improved antioxidant activity in vitro and in vivo by activation of superoxide dismutase (SOD) and glutathione (GSH). These results suggested that fucoidan could protect PC12 cells from apoptosis and ameliorate the learning and memory impairment in AD model mice, which appeared to be due to regulating the cholinergic system, reducing oxidative stress, and inhibiting the caspase-dependent apoptosis pathway.

Protective role of phenylethanoid glycosides, Torenoside�B and Savatiside A, in Alzheimer's disease

“…In the current study, Aβ 25-35 was used to induce SH-SY5Y cells at different concentrations. The results revealed a marked decrease in cell viability with increased Aβ 25-35 concentrations, which is consistent with the results of previous studies (21,22). To avoid adverse effects following induction, 30 µM of Aβ [25][26][27][28][29][30][31][32][33][34][35] (with a cell viability of 63.4%) was selected for subsequent cell-based in-vitro experiments.…”

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.…”

Study on Absorption Mechanism and Tissue Distribution of Fucoidan

“…Heart, liver, spleen, lung, kidney, and brain tissue were collected and homogenized. Tissue homogenate and plasma were added with 0, 0.2, 0.4, 0.8, 1, 2, 4, 6,8,10,15,20,25,30,35,40,45,50,60,80 and 100 µL of FITC solutions respectively to obtain FITC-tissue homogenate mixture. The fluorescence intensity was measured at 490 nm and 520 nm using a microplate reader.…”

“…The SO4 2− is the main functional group responsible for the biological properties of polysaccharides, and its quantity and position are critical determinants of the activity of these macromolecules. Recent studies have shown that fucoidan can exert a wide range of pharmacological effects, including anti-inflammatory [6], antitumor [7], antioxidative [8], antiviral, and antithrombotic activity, as well as improving immune response and lipid metabolism [5,[9][10][11][12]. However, only a small number of studies addressed the mechanism of absorption and tissue distribution of this compound in vivo given their high molecular size [13][14][15][16].…”