Fucoxanthin, a natural carotenoid abundant in edible brown seaweeds, has been shown to possess anti-cancer, anti-oxidant, anti-obesity and anti-diabetic effects. In this study, we report for the first time that fucoxanthin effectively protects against scopolamine-induced cognitive impairments in mice. In addition, fucoxanthin significantly reversed the scopolamine-induced increase of acetylcholinesterase (AChE) activity and decreased both choline acetyltransferase activity and brain-derived neurotrophic factor (BDNF) expression. Using an in vitro AChE activity assay, we discovered that fucoxanthin directly inhibits AChE with an IC₅₀ value of 81.2 μM. Molecular docking analysis suggests that fucoxanthin likely interacts with the peripheral anionic site within AChE, which is in accordance with enzymatic activity results showing that fucoxanthin inhibits AChE in a non-competitive manner. Based on our current findings, we anticipate that fucoxanthin might exhibit great therapeutic efficacy for the treatment of Alzheimer’s disease by acting on multiple targets, including inhibiting AChE and increasing BDNF expression.

Brain derived neurotrophic factor (BDNF) has been known to play an important role in various mental disorders or diseases such as Alzheimer's disease (AD). The aim of our study was to assess whether BDNF promoter methylation in peripheral blood was able to predict the risk of AD. A total of 44 AD patients and 62 age- and gender-matched controls were recruited in the current case-control study. Using the bisulphite pyrosequencing technology, we evaluated four CpG sites in the promoter of the BDNF. Our results showed that BDNF methylation was significantly higher in AD cases than in the controls (CpG1: p = 10.021; CpG2: p = 0.002; CpG3: p = 0.007; CpG4: p = 0.005; average methylation: p = 0.004). In addition, BDNF promoter methylation was shown to be significantly correlated with the levels of alkaline phosphatase (ALP), glucose, Lp(a), ApoE and ApoA in males (ALP: r = −0.308, p = 0.042; glucose: r = −0.383, p = 0.010; Lp(a): r = 0.333, p = 0.027; ApoE: r = −0.345, p = 0.032;), ApoA levels in females (r = 0.362, p = 0.033), and C Reactive Protein (CRP) levels in both genders (males: r = −0.373, p = 0.016; females: r = −0.399, p = 0.021). Our work suggested that peripheral BDNF promoter methylation might be a diagnostic marker of AD risk, although its underlying function remains to be elaborated in the future.

Alzheimer’s disease (AD), the most common neurodegenerative disorder, is characterized by neurofibrillary tangles, synaptic impairments, and loss of neurons. Oligomers of β‐amyloid (Aβ) are widely accepted as the main neurotoxins to induce oxidative stress and neuronal loss in AD. In this study, we discovered that fucoxanthin, a marine carotenoid with antioxidative stress properties, concentration dependently prevented Aβ oligomer‐induced increase of neuronal apoptosis and intracellular reactive oxygen species in SH‐SY5Y cells. Aβ oligomers inhibited the prosurvival phosphoinositide 3‐kinase (PI3K)/Akt cascade and activated the proapoptotic extracellular signal‐regulated kinase (ERK) pathway. Moreover, inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen‐activated protein kinase (MEK) synergistically prevented Aβ oligomer‐induced neuronal death, suggesting that the PI3K/Akt and ERK pathways might be involved in Aβ oligomer‐induced neurotoxicity. Pretreatment with fucoxanthin significantly prevented Aβ oligomer‐induced alteration of the PI3K/Akt and ERK pathways. Furthermore, LY294002 and wortmannin, two PI3K inhibitors, abolished the neuroprotective effects of fucoxanthin against Aβ oligomer‐induced neurotoxicity. These results suggested that fucoxanthin might prevent Aβ oligomer‐induced neuronal loss and oxidative stress via the activation of the PI3K/Akt cascade as well as inhibition of the ERK pathway, indicating that further studies of fucoxanthin and related compounds might lead to a useful treatment of AD.

Alzheimer’s disease (AD) is one of the most common diseases in elderly people with a high incidence of dementia at approximately 60–80%. The pathogenesis of AD was quite complicated and currently there is no unified conclusion in the academic community, so no efficiently clinical treatment is available. In recent years, with the development of traditional Chinese medicine (TCM), researchers have proposed the idea of relying on TCM to prevent and treat AD based on the characteristic of multiple targets of TCM. This study reviewed the pathological hypothesis of AD and the potential biomarkers found in the current researches. And the potential targets of berberine and evodiamine fromEvodia rutaecarpain AD were summarized and further analyzed. A compound-targets-pathway network was carried out to clarify the mechanism of action of berberine and evodiamine for AD. Furthermore, the limitations of current researches on the TCM and AD were discussed. It is hoped that this review will provide some references for development of TCM in the prevention and treatment of AD.