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Neuroprotective effects of fucoxanthin and its derivative fucoxanthinol from the phaeophyte Undaria pinnatifida attenuate oxidative stress in hippocampal neurons

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Neuroprotective and neurotrophic supports are critical for neuronal survival, outgrowth, and functional activity in the degenerating brain where oxidative stress is a leading cause of neurological disorders. An ethanol extract of the phaeophyte Undaria pinnatifida (UPE) concentration dependently increased the viability of rat hippocampal neurons in both hypoxia-induced oxidative stress and normoxic conditions. UPE, at an optimal 15 μg mL⁻¹, significantly reduced reactive oxygen species formation, DNA fragmentation, early and late apoptosis rates, and mitochondrial membrane dysfunction against hypoxia. In addition, the most active neuroprotectant from UPE was identified as fucoxanthin (Fx) by reverse-phase high-pressure liquid chromatography (RP-HPLC) and ¹H NMR. Fucoxanthinol (FxOH), a metabolite after enzymatic hydrolysis of Fx, significantly provided protection from neurite breakage and also enhanced the length of neurites in hypoxia cultures. The findings suggest that UPE and its active component Fx as well as FxOH have the ability to protect central nervous system neurons through anti-excitatory and anti-oxidative actions.
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Neuroprotective effects of fucoxanthin and its derivative fucoxanthinol
from the phaeophyte Undaria pinnatifida attenuate oxidative stress
in hippocampal neurons
Md. Mohibbullah
&Md. Nazmul Haque
&Mohammed Nurul Absar Khan
&In-Sik Park
&Il Soo Moon
Yong-Ki Hong
#Springer Science+Business Media B.V., part of Springer Nature 2018
Neuroprotective and neurotrophic supports are critical for neuronal survival, outgrowth, and functional activity in the
degenerating brain where oxidative stress is a leading cause of neurological disorders. An ethanol extract of the phaeophyte
Undaria pinnatifida (UPE) concentration dependently increased the viability of rat hippocampal neurons in both hypoxia-
induced oxidative stress and normoxic conditions. UPE, at an optimal 15 μgmL
, significantly reduced reactive oxygen species
formation, DNA fragmentation, early and late apoptosis rates, and mitochondrial membrane dysfunction against hypoxia. In
addition, the most active neuroprotectant from UPE was identified as fucoxanthin (Fx) by reverse-phase high-pressure liquid
chromatography (RP-HPLC) and
H NMR. Fucoxanthinol (FxOH), a metabolite after enzymatic hydrolysis of Fx, significantly
provided protection from neurite breakage and also enhanced the length of neurites in hypoxia cultures. The findings suggest that
UPE and its active component Fx as well as FxOH have the ability to protect central nervous system neurons through anti-
excitatory and anti-oxidative actions.
Keywords Fucoxanthin .Fucoxanthinol .Hippocampal neuron .Hypoxia .Undaria pinnatifida .Phaeophyta
Age-related brain disorders are of major concern among el-
derly individuals as life expectancy is increasing. Oxidative
stress in the brain is a prime initiator in almost all age-
associated neurological diseases including Alzheimers,
Parkinsons, and Huntingtons diseases (Uttara et al. 2009).
Moreover, the death of hippocampal neurons is closely asso-
ciated with a prolonged and severe oxidative stress, which is
ultimately linked to age-related memory impairment and dis-
orientation (Nicolle et al. 2001). However, the underlying
causes of such functional loss in neurodegenerative diseases
are still not clear. Neurons are highly susceptible to excess
levels of free radicals and, in turn, neurodegenerative diseases
can occur with the generation of oxidative stress-mediated
reactive oxygen species (ROS) that accompany mitochondrial
dysfunction leading to DNA fragmentation in the central ner-
vous system (CNS) underlying apoptosis or necrosis (Higuchi
2003; Suski et al. 2012). Since long-term treatment with tra-
ditional drugs such as donepezil, rivastigmine, and galanta-
mine might cause adverse effects in patients with neurodegen-
erative complications (Ali et al. 2015), many researchers are
trying to find natural products which are able to prevent ROS
formation in neurons.
Early efforts to investigate potential neurotrophic activity
of seaweeds showed that the brown seaweed Undaria
pinnatifida (known as miyok in Korea or wakame in Japan)
promoted neuronal cytoarchitectural complexity and function-
al maturation in rat hippocampal neurons (Hannan et al. 2014;
Bhuiyan et al. 2015). This seaweed is also known to prevent
*Yong -K i H on g
Department of Biotechnology, Pukyong National University,
Namgu, Busan 48513, Republic of Korea
Department of Anatomy, College of Medicine, Dongguk University,
Gyeongju, Gyeongbuk 38066, Republic of Korea
Department of Fishing & Post-Harvest Technology, Chittagong
Veterinary and Animal Sciences University, Chittagong, Bangladesh
Department of Anatomy, College of Korean Medicine, Dongguk
University, Gyeongju, Gyeongbuk 38066, Republic of Korea
Journal of Applied Phycology (2018) 30:32433252
Received: 19 O ctober 2017 / Revised and accepted: 15 March 201 8 / Pu blished online: 27 March 2018
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Phycobiliproteins (phycobilin at 100 or 500 µg/mL) and chlorophyll a at 245 µg/mL from P. palmata revealed anti-inflammatory properties by decreasing inflammatory mediators, namely IL-6, TNF-α, and • NO, in LPS-stimulated murine macrophages (RAW 264.7 cells) [310] (Table 4 [310][311][312][313][314][315][316]). Phycocyanin (48 mg/mL) stimulated the oxidative stress response in a yeast model of PD (alpha-synuclein induced toxicity) by modulating transcript levels of genes related to oxidative stress, such as SOD2 and HAP4 [311]. ...
... During the metabolism of fucoxanthin, it is deacetylated by lipase and esterase from the pancreas or in intestinal cells into fucoxanthinol [338]. Fucoxanthin at 0.075 µg/mL and this derivative, at the same concentration, showed antioxidant effects in primary cultures of rat hippocampal neurons against hypoxia-induced oxidative stress [312] (Table 4). ...
... [310][311][312][313][314][315][316]). Phycocyanin (48 mg/mL) stimulated the oxidative stress ...
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Currently, there is no known cure for neurodegenerative disease. However, the available therapies aim to manage some of the symptoms of the disease. Human neurodegenerative diseases are a heterogeneous group of illnesses characterized by progressive loss of neuronal cells and nervous system dysfunction related to several mechanisms such as protein aggregation, neuroinflammation, oxidative stress, and neurotransmission dysfunction. Neuroprotective compounds are essential in the prevention and management of neurodegenerative diseases. This review will focus on the neurodegeneration mechanisms and the compounds (proteins, polyunsaturated fatty acids (PUFAs), polysaccharides, carotenoids, phycobiliproteins, phenolic compounds, among others) present in seaweeds that have shown in vivo and in vitro neuroprotective activity. Additionally, it will cover the recent findings on the neuroprotective effects of bioactive compounds from macroalgae, with a focus on their biological potential and possible mechanism of action, including microbiota modulation. Furthermore, gastrointestinal digestion, absorption, and bioavailability will be discussed. Moreover, the clinical trials using seaweed-based drugs or extracts to treat neurodegenerative disorders will be presented, showing the real potential and limitations that a specific metabolite or extract may have as a new therapeutic agent considering the recent approval of a seaweed-based drug to treat Alzheimer’s disease.
... The administration of fucoxanthin to humans significantly reduces the relative body weight in a double-blind placebo-controlled study [15], along with in vitro [16] and in vivo [17] findings. Furthermore, fucoxanthin acts as a neurotrophic factor-like substance, conferring neuroprotection [18] and neurite outgrowth [19] in CNS neurons. In addition, fucoxanthin can ameliorate metabolic [3], hepatic [9], renal [20], cardiovascular [21], bone [22], ocular [23], skin [24], and respiratory [25] diseases, and show antimicrobial potentials [26]. ...
... Fucoxanthin suppresses OGD/R-induced apoptosis and ROS accumulation in cultured neurons, via activating the Nrf2/HO-1 signaling [90]. Neuroprotective effects were reported in hypoxia/reoxygenation (H/R)-induced excitotoxicity in primary hippocampal neurons when fucoxanthin and its derivative of fucoxanthinol were added to the culture [19]. Fucoxanthin also alleviated cerebral ischemic/reperfusion (I/R) injury and improved the neurologic deficit [90]. ...
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Fucoxanthin, belonging to the xanthophyll class of carotenoids, is a natural antioxidant pigment of marine algae, including brown macroalgae and diatoms. It represents 10% of the total carotenoids in nature. The plethora of scientific evidence supports the potential benefits of nutraceu-tical and pharmaceutical uses of fucoxanthin for boosting human health and disease management. Due to its unique chemical structure and action as a single compound with multi-targets of health effects, it has attracted mounting attention from the scientific community, resulting in an escalated number of scientific publications from January 2017 to February 2022. Fucoxanthin has remained the most popular option for anti-cancer and anti-tumor activity, followed by protection against in-flammatory, oxidative stress-related, nervous system, obesity, hepatic, diabetic, kidney, cardiac, skin, respiratory and microbial diseases, in a variety of model systems. Despite much pharmacological evidence from in vitro and in vivo findings, fucoxanthin in clinical research is still not satisfactory , because only one clinical study on obesity management was reported in the last five years. Additionally, pharmacokinetics, safety, toxicity, functional stability, and clinical perspective of fu-coxanthin are substantially addressed. Nevertheless, fucoxanthin and its derivatives are shown to be safe, non-toxic, and readily available upon administration. This review will provide pharmacological insights into fucoxanthin, underlying the diverse molecular mechanisms of health benefits. However, it requires more activity-oriented translational research in humans before it can be used as a multi-target drug.
... Fucoxanthin is a major pigment present in brown algae (Xiao et al., 2012) and it has been well reported to possess a broad spectrum of pharmacological properties including antioxidant, anti-inflammatory, neuroprotector, and antiobesity activity (Peng et al., 2011;Gammone and D'Orazio, 2015;Mohibbullah et al., 2018). Carotenoids and phenolics in macroalgae have been proven to be associated with antioxidant activity, with eISSN: 2550-2166 © 2021 The Authors. ...
... Published by Rynnye Lyan Resources FULL PAPER fucoxanthin being the lead compound responsible for this (Foo et al., 2017). Fucoxanthin harbours alenic and 5,6-monoepoxide bonds (Miyashita et al., 2011;Shang et al., 2011) that is responsible for various pharmacological effects, including anti-oxidant (Yu et al., 2018) which is achieved by scavenging free radicals (Foo et al., 2017;Mohibbullah et al., 2018). ...
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Fucoxanthin from brown algae has potential as a promising functional food component. However, fucoxanthin is less stable under high temperature and light exposure. The purpose of this study was to analyse the effect of stevia and cacao butter in increasing the stability of Sargassum polycystum C. Agardh extract containing fucoxanthin and its application as a snack bar. Brown algae, S. polycystum, was extracted using 96% foodgrade ethanol. Antioxidant activity and stability assay were performed using the 2,2- Diphenyl-1-Picrylhydrazyl (DPPH) method. Antioxidant activity of both, extract (E) and extract + stevia (ES), was found to decrease with time. Meanwhile, cacao butter was able to maintain extract’s stability without any significant difference when compared to extract alone. A combination of extract, stevia, and cacao butter (ESC) were found to be able to maintain antioxidant stability. Formulation of a snack bar with cacao butter and 1% stevia were more preferred by the panellists when compared to the other formulations. This study reports that cacao butter and 1% stevia is able to maintain antioxidant stability and improve the economic value of S. polycystum, one of them through the formulations of the snack bar.
... Moreover, to confirm the actions of extracts containing violaxanthin, concentrations of ∼1.8 and ∼2.8 μg ml −1 were investigated and also found to inhibit proliferation of colon cancer cells, thus confirming earlier research performed by Pasquet et al. (2011) with violaxanthin from Dunaliella tertiolecta (Pasquet et al. 2011), andCha et al. 2008, with violaxanthin from Chlorella ellipsoidea (Cha et al. 2008). It has also been observed that fucoxanthin and its derivative, fucoxanthinol (8-oxo-trans-neoxanthin; C 40 H 56 O 5 ), obtained from U. pinnatifida (15 μg ml −1 ) exhibited neuroprotective effects on rat hippocampal neurons in both hypoxia-induced oxidative stress and normoxic conditions through antiexcitatory and antioxidative actions (Mohibbullah et al. 2018), which could be of interest in the prevention of neurodegenerative diseases. ...
... Mechanisms and strategies for safe and effective neuroprotection against several types of damage, apoptosis, dysfunction, and degeneration of the central nervous system should therefore be developed . The neuroprotective action of certain algal compounds has been studied in recent years and examples of these are: pigments such as fucoxanthin, probably due to its antioxidant capacity Mohibbullah et al. 2018), and pheophytin, which promotes neuronal development in embryogenesis. Pheophytin did not itself promote neurite outgrowth of PC12 cells. ...
Macro‐ and microalgae contain a variety of biologically active compounds that are of great interest in the prevention of diseases and therefore are potential candidates for the development of pharmaceutical preparations, either as medicines or as nutraceuticals. Some epidemiological studies indicate that consumption of algae can protect from certain diseases such as allergies, cardiovascular diseases, cancer, obesity, diabetes, high blood pressure, atopic dermatitis, or Alzheimer's disease, and this has led to in vitro and in vivo studies, to research their possible mechanisms of action. Even though clinical trials are scarce, the pharmaceutical industry is keen on developing drugs of natural origin from marine organisms (e.g. Adcetris®), with fewer side effects or less toxicity to humans. Macro‐ and microalgae contain a variety of bioactive compounds: polysaccharides; phenolic compounds such as phlorotannins; diverse pigments such as the chlorophylls and carotenoids, including fucoxanthin; mycosporine‐like amino acids; halogenated compounds; proteins, peptides, and amino acids; essential and long‐chain marine polyunsaturated fatty acids; sterols; and other lipids, vitamins, and minerals that could be putative active ingredients for the pharmaceutical industry. Moreover, the cosmetics industry is studying algal compounds as a source of ingredients for potential use in cosmeceutical preparations such as phloroglucinol, porphyran, astaxanthin, and fucoxanthin. This chapter summarizes current knowledge on algal compounds of interest for the formulation of pharmaceutical and cosmeceutical preparations.
... Reduction of oxidative stress in rat hippocampal neurons [40]; Increase in neuron survivals in traumatic brain injury models [41] Mytiloxanthin (metabolite of fucoxanthin) Tunicates and shellfish Scavenger of singlet oxygen [42] Lipids Polyunsaturated fatty acids fish oils (cod liver oil), algae, sea cucumber, microalgae ...
... Reduction of Aβ-amyloid toxicity, anti-aggregation properties, inhibition of Aβ 40 Reduction of neuronal cell apoptosis and pro-inflammatory cytokines, neuroprotective effect in cerebral ischemia in gerbils [45]; amelioration of brain condition after stroke [46] crabs (Goniopsis cruentata and Ucides cordatus), sea cucumber, ascidian (Styela plicata), scallop, cockle (Cerastoderma edule), sand dollar (Mellita quinquiesperforata) ...
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Marine habitats offer a rich reservoir of new bioactive compounds with great pharmaceutical potential; the variety of these molecules is unique, and its production is favored by the chemical and physical conditions of the sea. It is known that marine organisms can synthesize bioactive molecules to survive from atypical environmental conditions, such as oxidative stress, photodynamic damage, and extreme temperature. Recent evidence proposed a beneficial role of these compounds for human health. In particular, xanthines, bryostatin, and 11-dehydrosinulariolide displayed encouraging neuroprotective effects in neurodegenerative disorders. This review will focus on the most promising marine drugs’ neuroprotective potential for neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. We will describe these marine compounds’ potential as adjuvant therapies for neurodegenerative diseases, based on their antioxidant, anti-inflammatory, and anti-apoptotic properties.
... Its protective effect on the gastric mucosa was also evaluated in this study. Activities of the two enzymes, serum aspartate transaminase (AST) and alanine transaminase (ALT), were lowered by FX treatment, indicating its positive effect on alcohol-induced liver injury (Mohibbullah et al., 2018;Zheng et al., 2019). Fat deposition in alcohol-induced liver was effectively reduced by FX. ...
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Fucoxanthin (FX) is a special carotenoid having an allenic bond in its structure. FX is extracted from a variety of algae and edible seaweeds. It has been proved to contain numerous health benefits and preventive effects against diseases like diabetes, obesity, liver cirrhosis, malignant cancer, etc. Thus, FX can be used as a potent source of both pharmacological and nutritional ingredient to prevent infectious diseases. In this review, we gathered the information regarding the current findings on antimicrobial, antioxidant, anti-inflammatory, skin protective, anti-obesity, antidiabetic, hepatoprotective, and other properties of FX including its bioavailability and stability characteristics. This review aims to assist further biochemical studies in order to develop further pharmaceutical assets and nutritional products in combination with FX and its various metabolites.
... It reduces inflammation, decreases oxidative stress, and has an antiobesity effect, demonstrating its safety for use in animals and humans [8][9][10][11]. Moreover, fucoxanthin reduces Aβ-induced oxidative stress and proinflammatory cytokines in microglial cells and hippocampal neurons [12,13], inhibits Aβ aggregation, and alleviates cognitive impairment in vivo [14]. Additionally, the fluorescence spectrum of fucoxanthin has absorption bands at 448, 476, and 505 nm and emission bands at 630, 685, and 750 nm [15]. ...
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The visualization of misfolded Aβ peptides by using fluorescence chemical dyes is very important in Alzheimer’s disease (AD) diagnosis. Here, we describe the fluorescent substance, fucoxanthin, which detects Aβ aggregates in the brain of AD transgenic mouse models. We found that fucoxanthin from the microalgae Phaeodactylum tricornutum has fluorescent excitation and emission wavelengths without any interference for Aβ interaction. Thus, we applied it to monitor Aβ aggregation in AD transgenic mouse models. Aβ plaques were visualized using fucoxanthin in the brain tissue of APP/PS1 and 5×FAD mice by histological staining with different staining methods. By comparing fucoxanthin-positive and thioflavin S-positive stained regions in the brains, we found that they are colocalized and that fucoxanthin can detect Aβ aggregates. Our finding suggests that fucoxanthin from P. tricornutum can be a new Aβ fluorescent imaging reagent in AD diagnosis.
Macroalgal pigments can serve as indicators of an environmental stresses due to their higher accumulation during these conditions. Even though they exhibit protective role, a stress can cause their degradation. Many factors influence the pigment content in macroalgae including the temperature of seawater, salinity and acidification, but they are also dependent on macroalgal species. Brown macroalgae are known for their fucoxanthin content, red macroalgae are characterized by the presence of phycobiliproteins, while green macroalgae contain highest chlorophylls amount. This review reports the main pigments isolated from three different macroalgal groups including brown (Ochrophyta), red (Rhodophyta) and green (Chlorophyta) macroalgae along with their bioactivities for the period 2016–2021. The methods of their isolation and analysis are systematically represented with an emphasis on comparison between the conventional and innovative extraction methods. The pigments antioxidant, neuroprotective, cytotoxic, anticancer, anti-inflammatory, anti-hypertensive activities and others are summarized indicating the potential of targeted macroalgal species for being used as the sources of these bioactive compounds.
The fucoxanthin is a high-added-value compound that corresponds to the category of carotenoids. It has been extracted from marine sources and for several different extraction methods in various countries. Fucoxanthin applications are in different areas, such as the pharmaceutical, cosmetic, and food industries. However, recent research has shown that fucoxanthin has anticancer, antioxidant, anti-obesity, anti-diabetic, hypoglycemic, and neuroprotective activities, which suggest its use as a food supplement. Finally, this review aims to show the latest advances of fucoxanthin from seaweeds in the extraction process, chemical characterization, and bioactivities in the development of third generation biorefineries and circular bioeconomy. This article is protected by copyright. All rights reserved.
Neuroinflammation is one of the key events in the progression of multiple neurological disorders. The blood–brain barrier and blood–nerve barrier are responsible for the development of neuroinflammation via metabolic alteration, free radical generation, and lipid peroxidation. Furthermore, overexpression of biological proteins such as proinflammatory and proapoptotic mediators, activation of glial, astrocyte, oligodendrocyte, and Schwann cells also plays a key role in the development of neuroinflammation. Moreover, in some cases, alteration of cellular enzymes, ion channels, and prion proteins are also used to enhance neuroinflammation. The natural source of medicines such as plant, animal, marine, and mineral drugs plays a critical role in ameliorating the free radical, lipid peroxidation, and inflammatory cytokine-associated neuroinflammation. Some conventional medicines are involved in the regulation of neurotransmitters and ion channel function in the nervous system. However, the clinical use of conventional medicines is still questionable due to its low safety, efficacy, and higher intolerable adverse effects. The recent drug discovery process has paid greater attention toward natural medicines especially marine drugs for neuroinflammatory disorders. Some of the marine drugs have a promising role in the management of neurovascular disorders via potential antiinflammatory actions. However, the relationship between chemical structure and their biological activity remains to be explored. It is an essential part of bringing potential medicines from nature to health management. Hence, this book chapter is based on exploring the structure–activity relationship of marine drugs for neuroinflammatory disorders.
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Background: As a natural carotenoid abundant in chloroplasts of edible brown algae, fucoxanthin possesses various health benefits, including anti-oxidative activity in particular. Objective: In the present study, we studied whether fucoxanthin protected against hydrogen peroxide (H2O2)-induced neuronal apoptosis. Design: The neuroprotective effects of fucoxanthin on H2O2-induced toxicity were studied in both SH-SY5Y cells and primary cerebellar granule neurons. Results: Fucoxanthin significantly protected against H2O2-induced neuronal apoptosis and intracellular reactive oxygen species. H2O2 treatment led to the reduced activity of phosphoinositide 3-kinase (PI3-K)/Akt cascade and the increased activity of extracellular signal-regulated kinase (ERK) pathway in SH-SY5Y cells. Moreover, fucoxanthin significantly restored the altered activities of PI3-K/Akt and ERK pathways induced by H2O2. Both specific inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase kinase (MEK) significantly protected against H2O2-induced neuronal death. Furthermore, the neuroprotective effects of fucoxanthin against H2O2-induced neuronal death were abolished by specific PI3-K inhibitors. Conclusions: Our data strongly revealed that fucoxanthin protected against H2O2-induced neurotoxicity via concurrently activating the PI3-K/Akt cascade and inhibiting the ERK pathway, providing support for the use of fucoxanthin to treat neurodegenerative disorders induced by oxidative stress.
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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.
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This survey analyzes two national pharmacovigilance databases in order to determine the major adverse reactions observed with the use of cholinesterase inhibitors in dementia. We conducted a statistical analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction Database (CVARD) concerning the side effects of cholinesterase inhibitors. The statistics calculated for each adverse event were the frequency and the reporting odds ratios (ROR). A total of 9877 and 2247 reports were extracted from the FAERS and CVARD databases, respectively. A disproportionately higher frequency of reports of death as an adverse event for rivastigmine, compared to the other acetylcholinesterase inhibiting drugs, was observed in both the FAERS (ROR = 3.42; CI95% = 2.94-3.98; P<0.0001) and CVARD (ROR = 3.67; CI95% = 1.92-7.00; P = 0.001) databases. While cholinesterase inhibitors remain to be an important therapeutic tool against Alzheimer's disease, the disproportionate prevalence of fatal outcomes with rivastigmine compared with alternatives should be taken into consideration.
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Reductions in neurotrophic factors are implicated in synaptic dysfunction in the central nervous system, but exogenous neurotrophic factors with potential effects on neuritic regeneration and synaptic reconstruction could offer therapeutic and preventive strategies for treating memory-related neurological disorders. In an earlier effort to identify natural neurotrophic agents, we found that the ethanol extract of the edible marine alga Undaria pinnatifida (UPE) had promising effects on the neuritogenesis of cultured hippocampal neurons. Here, we further investigated the ability of UPE to promote spinogenesis and synaptogenesis in primary cultures of hippocampal neurons. It was found that UPE triggered significant increase in numbers of dendritic filopodia and spines, promoted the formation of excitatory and inhibitory synapses, and potentiated synaptic transmission by increasing the sizes of reserve vesicle pools at presynaptic terminals. These findings indicate a substantial role for UPE in the morphological and functional maturation of neurons and suggest that UPE is a possible therapeutic preventative measure and treatment for neurodegenerative diseases, such as those involving cognitive disorders and memory impairments.
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Age-related neurological disorders are of growing concern among the elderly, and natural products with neuroprotective properties have been attracting increasing attention as candidates for the prevention or treatment of neurological disorders induced by oxidative stress. In an effort to explore natural resources, we collected some common marine seaweed from the Korean peninsula and Indonesia and screened them for neuroprotective activity against hypoxia/reoxygenation (H/R)-induced oxidative stress. Of the 23 seaweeds examined, the ethanol extract of Gracilariopsis chorda (GCE) provided maximum neuroprotection at an optimum concentration of 15 μg/mL, followed by Undaria pinnatifida. GCE increased cell viability after H/R, decreased the formation of reactive oxygen species (measured by 2',7'-dichlorodihydrofluorescein diacetate [DCF-DA] staining), and inhibited the double-stranded DNA breaks (measured by H2AX immunocytochemistry), apoptosis (measured by Annexin V/propidium iodide staining), internucleosomal DNA fragmentation (measured by DNA laddering), and dissipation of mitochondrial membrane potential (measured by JC-1 staining). Using reverse-phase high-pressure liquid chromatography, we quantitated the arachidonic acid (AA) in GCE, which provides neuroprotection against H/R-induced oxidative stress. This neuroprotective effect of AA was comparable to that of GCE. These findings suggest that the neuroprotective effect of GCE against H/R-induced neuronal death is due, at least in part, to the AA content that suppresses neuronal apoptosis.
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Histone H2AX is a ubiquitous member of the H2A histone family that differs from the other H2A histones by the presence of an evolutionarily conserved C-terminal motif, -KKATQASQEY. The serine residue in this motif becomes rapidly phosphorylated in cells and animals when DNA double-stranded breaks are introduced into their chromatin by various physical and chemical means. In the present communication we show that this phosphorylated form of H2AX, referred to as γ-H2AX, appears during apoptosis concurrently with the initial appearance of high molecular weight DNA fragments. γ-H2AX forms before the appearance of internucleosomal DNA fragments and the externalization of phosphatidylserine to the outer membrane leaflet. γ-H2AX formation is inhibited byN-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone and the inhibitor of caspase-activated DNase, and it is induced when DNase I and restriction enzymes are introduced into cells, suggesting that any apoptotic endonuclease is sufficient to induce γ-H2AX formation. These results indicate that γ-H2AX formation is an early chromatin modification following initiation of DNA fragmentation during apoptosis.
This study explored Himanthalia elongata brown seaweed as a potential source of dietary fucoxanthin which is a promising medicinal and nutritional ingredient. The seaweed was extracted with low polarity solvents (n-hexane, diethyl ether, and chloroform) and the crude extract was purified with preparative thin layer chromatography (P-TLC). Identification, quantification and structure elucidation of purified compounds was performed by LC-DAD-ESI-MS and NMR (1H and 13C). P-TLC led purification yielded 18.6 mg/g fucoxanthin with 97% of purity based on the calibration curve, in single-step purification. LC-ESI-MS (parent ion at m/z 641 [M + H-H2O]+) and NMR spectra confirmed that the purified band contained all-trans-fucoxanthin as the major compound. Purified fucoxanthin exhibited statistically similar (p > 0.05) DPPH scavenging capacity (EC50: 12.9 μg/mL) while the FRAP value (15.2 μg trolox equivalent) was recorded lower (p < 0.05) than the commercial fucoxanthin. The promising results of fucoxanthin purity, recovery and activity suggested that H. elongata seaweed has potential to be exploited as an alternate source for commercial fucoxanthin production.
To extend the scope of application of fucoxanthin, a marine carotenoid, whole milk (WM) and skimmed milk (SM) were fortified with fucoxanthin isolated from the microalga Phaeodactylum tricornutum to a final 8 μg/mL milk solution concentration. Using these liquid systems, a fucoxanthin analysis method implementing extraction and HPLC-DAD was developed and validated by accuracy, precision, system suitability, and robustness tests. The current method demonstrated good linearity over the range of 0.125-100 μg/mL fucoxanthin with R(2) = 1.0000, and all validation data supported its adequacy for use in fucoxanthin analysis from milk solution. To investigate fucoxanthin stability during milk production and distribution, fucoxanthin content was examined during storage, pasteurization, and drying processes under various conditions. Fucoxanthin in milk solutions showed better stabilizing effect in 1 month of storage period. Degradation rate constant (k) on fucoxanthin during this storage period suggested that fucoxanthin stability might be negatively correlated with decrease of temperature and increase of protein content such as casein and whey protein in milk matrix. In a comparison between SM and WM, fucoxantin in SM always showed better stability than that in WM during storage and three kinds of drying processes. This effect was also deduced to relate with protein content. In the pasteurization step, >91% of fucoxanthin was retained after three pasteurization processes even though the above trend was not found. This study demonstrated for the first time that milk products can be used as a basic food matrix for fucoxanthin application and that protein content in milk is an important factor for fucoxanthin stability.