Table 4:

Potentially protective biological activity of seaweed in neurodegenerative diseases.

Study type	Model	Treatment	Main findings	Reference
In vitro	Rat PC12 neuronal cell model of AD	Phlorotannin extracted from Ecklonia radiata for 48 h	Inhibits in vitro Aβ1–42 aggregation by 90%	Alghazwi et al. (2020)
			Reduces Aβ1–42-induced apoptosis threefold
	Murine N2a-sw neuronal cell model of AD	Unsaturated mannuronate oligosaccharide (1 mg/ml) for 24 h	Decreases Aβ1–42 production as measured by downregulated APP and BACE1 expression	Bi et al. (2021)
Animal	MPTP-induced C57BL/6J mouse model of PD	Oral administration of polymannuronic acid (30 mg/kg) for 4 weeks	Improves motor functions as measured by increased survival of TH-IR neurons in SNpc	Dong et al. (2020)
			Exhibits anti-inflammatory effect in CNS as measured by suppressed IL-6 and TNF-α mRNA expression
			Enhances integrity of BBB and intestinal barrier as demonstrated by increased expression of occludin and ZO-1
	MPTP-induced C57BL/6J mouse model of PD	Oral administration of polymannuronic acid (30 mg/kg) for 4 weeks prior to MPTP	Increases survival of TH-IR neurons in the SNpc	Du et al. (2021)
			Improves motor function in pole test
			Increases striatal levels of serotonin and its metabolite 5-hydroxyindole acetic acid
	5XFAD transgenic mouse model of AD	Oral administration of GV-971 (100 mg/kg) for 1 month	Normalizes fecal and blood phenylalanine and isoleucine concentrations	Wang et al. (2019)
			Decreases Th1 cells, reactive microglia, Aβ plaque deposition, and tau phosphorylation in the brain
	APP/PS1 mouse model of AD	Oral administration of GV-971 (50 or 100 mg/kg) for 3 months	Improves cognitive functions as measured by enhanced spatial learning and memory performance	Wang et al. (2019)
Human clinical trials	Phase III clinical trial of patients with mild to moderate AD	Oral administration of GV-971 (450 mg) twice a day for 36 weeks	Improves ADAS-Cog12 score compared to baseline and patients who took a placebo	Xiao et al. (2021)

AD, Alzheimer’s disease; ADAS-Cog12, Alzheimer’s Disease Assessment Scale; APP, amyloid precursor protein; Aβ, amyloid β; BACE1, β-site APP cleaving enzyme 1; BBB, blood–brain barrier; CNS, central nervous system; IL, interleukin; MPTP, 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine; PD, Parkinson’s disease; PS1, presenilin 1; SNpc, substantia nigra pars compacta; Th1, type 1 T helper; TNF-α, tumor necrosis factor α; and ZO, zonula occludens.