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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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8TH ASIAN PACIFIC PHYCOLOGICAL FORUM
Neuroprotective effects of fucoxanthin and its derivative fucoxanthinol
from the phaeophyte Undaria pinnatifida attenuate oxidative stress
in hippocampal neurons
Md. Mohibbullah
1
&Md. Nazmul Haque
2
&Mohammed Nurul Absar Khan
1,3
&In-Sik Park
4
&Il Soo Moon
2
&
Yong-Ki Hong
1
#Springer Science+Business Media B.V., part of Springer Nature 2018
Abstract
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
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
1
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
Introduction
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
ykhong@pknu.ac.kr
1
Department of Biotechnology, Pukyong National University,
Namgu, Busan 48513, Republic of Korea
2
Department of Anatomy, College of Medicine, Dongguk University,
Gyeongju, Gyeongbuk 38066, Republic of Korea
3
Department of Fishing & Post-Harvest Technology, Chittagong
Veterinary and Animal Sciences University, Chittagong, Bangladesh
4
Department of Anatomy, College of Korean Medicine, Dongguk
University, Gyeongju, Gyeongbuk 38066, Republic of Korea
https://doi.org/10.1007/s10811-018-1458-6
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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... 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 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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... 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. ...
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... 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 ...
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