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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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Journal of Applied Phycology
Authors:
Md. Mohibbullah at Sher-e-Bangla Agricultural University
Md. Mohibbullah
Md Nazmul Haque Habib at Dongguk University
Md Nazmul Haque Habib
Mohammed Nurul Absar Khan at Chattogram Veterinary and Animal Sciences University
Mohammed Nurul Absar Khan
In-Sik Park
In-Sik Park
In-Sik Park
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Abstract and Figures

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.
Effect of UPE on neuronal viability in H/R and normal cultures. Embryonic (E) 19-day rat hippocampal cells were cultured and plated at 3 × 10⁴ cells cm⁻². On DIV 9, cultures were exposed to hypoxia (3 h) and subsequently to normoxia (96 h). a At the 13th day of cultures, a representative MAP-2 immunostained image to identify hippocampal neurons (a), neurons in normoxia (no H/R) control (b), neurons in hypoxia control (c), and neurons in the UPE (15 μg mL⁻¹) + hypoxia-treated group (d). Scale bar: 80 μm (a, (a)); 40 μm (a, (b–d)). b The viability was determined by trypan blue exclusion and LDH assays in both hypoxic (a) and normoxic (b) cultures. Bars represent means ± SE (n = 3; ~ 800–1000 neurons per group). #P < 0.05, ##P < 0.001 compared with the normoxia control; *P < 0.05, **P < 0.001 compared with the hypoxia control (ANOVA)
Effect of UPE on neuronal viability in H/R and normal cultures. Embryonic (E) 19-day rat hippocampal cells were cultured and plated at 3 × 10⁴ cells cm⁻². On DIV 9, cultures were exposed to hypoxia (3 h) and subsequently to normoxia (96 h). a At the 13th day of cultures, a representative MAP-2 immunostained image to identify hippocampal neurons (a), neurons in normoxia (no H/R) control (b), neurons in hypoxia control (c), and neurons in the UPE (15 μg mL⁻¹) + hypoxia-treated group (d). Scale bar: 80 μm (a, (a)); 40 μm (a, (b–d)). b The viability was determined by trypan blue exclusion and LDH assays in both hypoxic (a) and normoxic (b) cultures. Bars represent means ± SE (n = 3; ~ 800–1000 neurons per group). #P < 0.05, ##P < 0.001 compared with the normoxia control; *P < 0.05, **P < 0.001 compared with the hypoxia control (ANOVA)
… 
Effect of UPE on ROS formation after H/R. Vehicle or UPE (15 μg mL⁻¹) was added to the hippocampal cultures. On DIV 9, the cultures were exposed to hypoxia for different times and then to normoxia for 24 h. a Typical phase-contrast (upper) and DCF-DA-stained (lower) images. Scale bar = 40 μm. b Percentage of ROS(+) cells. Bars represent means ± SE (n = 3; ~ 1000–1200 neurons per group). *P < 0.01 compared with vehicle-treated controls (Student’s t test)
Effect of UPE on ROS formation after H/R. Vehicle or UPE (15 μg mL⁻¹) was added to the hippocampal cultures. On DIV 9, the cultures were exposed to hypoxia for different times and then to normoxia for 24 h. a Typical phase-contrast (upper) and DCF-DA-stained (lower) images. Scale bar = 40 μm. b Percentage of ROS(+) cells. Bars represent means ± SE (n = 3; ~ 1000–1200 neurons per group). *P < 0.01 compared with vehicle-treated controls (Student’s t test)
… 
Effect of UPE on DNA fragmentation after H/R. Cultures were exposed to hypoxia on DIV 6 and then to normoxia. a Representative immunostained images with the anti-phospho-H2AX antibody. Nuclei are enlarged to show individual puncta (arrowheads). Scale bar = 2 μm. b Number of puncta per nucleus was counted. Bars represent means ± SE (n = 30 nuclei). *P < 0.001 compared with normoxia and hypoxia controls (Student’s t test)
Effect of UPE on DNA fragmentation after H/R. Cultures were exposed to hypoxia on DIV 6 and then to normoxia. a Representative immunostained images with the anti-phospho-H2AX antibody. Nuclei are enlarged to show individual puncta (arrowheads). Scale bar = 2 μm. b Number of puncta per nucleus was counted. Bars represent means ± SE (n = 30 nuclei). *P < 0.001 compared with normoxia and hypoxia controls (Student’s t test)
… 
Effect of UPE on apoptosis formation and subsequent MMP loss after H/R. Cultures were exposed to hypoxia for 3 h and normoxia for 96 h. a Typical images of annexin V (AV; green) and propidium iodide (PI; red) double staining to visualize early [AV(+)/PI(−)] and late apoptotic [AV(+)/PI(+)] neurons, scale bar = 2 μm (a), and the proportion (%) of early and late apoptotic cells (b). b Representative images of JC-1 staining for MMP, scale bar = 8 μm (a), and the red/green intensity ratios (b). Bars represent means ± SE (n = 3; ~ 1500 neurons per group for apoptosis study and ~ 40 neurons per group for MMP). #P < 0.05, ##P < 0.001 compared with the normoxia control; *P < 0.05, **P < 0.001 compared with the hypoxia control (ANOVA)
Effect of UPE on apoptosis formation and subsequent MMP loss after H/R. Cultures were exposed to hypoxia for 3 h and normoxia for 96 h. a Typical images of annexin V (AV; green) and propidium iodide (PI; red) double staining to visualize early [AV(+)/PI(−)] and late apoptotic [AV(+)/PI(+)] neurons, scale bar = 2 μm (a), and the proportion (%) of early and late apoptotic cells (b). b Representative images of JC-1 staining for MMP, scale bar = 8 μm (a), and the red/green intensity ratios (b). Bars represent means ± SE (n = 3; ~ 1500 neurons per group for apoptosis study and ~ 40 neurons per group for MMP). #P < 0.05, ##P < 0.001 compared with the normoxia control; *P < 0.05, **P < 0.001 compared with the hypoxia control (ANOVA)
… 
RP-HPLC analysis of Fx in UPE and its neuroprotective activity in a dose-dependent manner against H/R injury. a Representative RP-HPLC chromatograms of UPE (a), Fx (b), and the mixture of UPE and Fx (c). Neurons were exposed to hypoxia for 3 h on DIV 9 and then to normoxia for 96 h. b Screening of each RP-HPLC fraction (F1, F2, and F3) of UPE for the ability to protect neurons against H/R. c Treatment of Fx with different concentrations ranging from 0.025 to 0.25 μg mL⁻¹. Cell viability was determined using the trypan blue exclusion assay on DIV 13. Bars represent means ± SE (n = 3; ~ 800–1000 neurons per group). #P < 0.01 compared with the normoxia control; *P < 0.05, **P < 0.01, ***P < 0.001 compared with the hypoxia control (ANOVA)
+2
RP-HPLC analysis of Fx in UPE and its neuroprotective activity in a dose-dependent manner against H/R injury. a Representative RP-HPLC chromatograms of UPE (a), Fx (b), and the mixture of UPE and Fx (c). Neurons were exposed to hypoxia for 3 h on DIV 9 and then to normoxia for 96 h. b Screening of each RP-HPLC fraction (F1, F2, and F3) of UPE for the ability to protect neurons against H/R. c Treatment of Fx with different concentrations ranging from 0.025 to 0.25 μg mL⁻¹. Cell viability was determined using the trypan blue exclusion assay on DIV 13. Bars represent means ± SE (n = 3; ~ 800–1000 neurons per group). #P < 0.01 compared with the normoxia control; *P < 0.05, **P < 0.01, ***P < 0.001 compared with the hypoxia control (ANOVA)
… 
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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 Alzheimer’s,
Parkinson’s, and Huntington’s 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) 30:3243–3252
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.
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Full-text available
  • Mar 2017
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 Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterase in Vitro
Article
Full-text available
  • Mar 2016
  • MAR DRUGS
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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Adverse Effects of Cholinesterase Inhibitors in Dementia, According to the Pharmacovigilance Databases of the United-States and Canada
Article
Full-text available
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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Undaria pinnatifida Promotes Spinogenesis and Synaptogenesis and Potentiates Functional Presynaptic Plasticity in Hippocampal Neurons
Article
Full-text available
  • May 2015
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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The Edible Marine Alga Gracilariopsis chorda Alleviates Hypoxia/Reoxygenation-Induced Oxidative Stress in Cultured Hippocampal Neurons
Article
Full-text available
  • Jun 2015
  • J MED FOOD
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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Initiation of DNA Fragmentation during Apoptosis Induces Phosphorylation of H2AX Histone at Serine 139
Article
Full-text available
  • Mar 2000
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.
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Rat Hippocampal Neurons in Low-Density Culture
Chapter
  • Sep 1998
A do-it-yourself manual for culturing nerve cells, complete with recipes and protocols. Because neurons and glia in culture are remarkably similar to those in situ, culture systems make it possible to identify significant cell interactions and to elucidate their mechanisms. This book is in many ways a do-it-yourself manual for culturing nerve cells, complete with recipes and protocols. But it also provides an understanding of the principles behind the protocols. In effect the contributors invite you into their labs and provide much of the information you would obtain from such a visit.The authors of the introductory chapters present the nuts-and-bolts principles of growing nerve cells. The authors of the following chapters discuss the culturing of specific cell types. They explain how their experimental goals have shaped their particular cell culture approach and the advantages and disadvantages of the cell culture systems they have developed. They provide detailed protocols and describe their cultures in practical terms, from when the cells are first plated through the various phases of their development. ContributorsJanet Alder, Hannelore Asmussen, Gerard Bain, Gary Banker, Robert W. Baughman, Richard P. Bunge, Ann Marie Craig, Matthew E. Cunningham, Dominique Debanne, Stephen E. Farinelli, Michael F.A. Finley, Gerald D. Fishbach, Beat H. Gähwiler, W.-Q. Gao, Daniel J. Goldberg, Kimberly Goslin, David I. Gottlieb, Lloyd A. Greene, Mary Beth Hatten, Dennis Higgins, James E. Huettner, Kenneth A. Jones, Naomi Kleitman, Raul Krauss, Ronald M. Lindsay, Nagesh K. Mahanthappa, Carol A. Mason, Margot Mayer-Pröschel, R. Anne McKinney, Mary E. Morrison, Mark Noble, David S. Park, Paul H. Patterson, Mu-ming Poo, Richard T. Robertson, Samuel Schacher, Michael M. Segal, Carolyn L. Smith, Nacira Tabti, Scott M. Thompson, Roseann Ventimiglia, Ginger S. Withers, Patrick M. Wood, Min Yao Bradford Books imprint
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Characterization of dietary fucoxanthin from Himanthalia elongata brown seaweed
Article
  • Sep 2016
  • FOOD RES INT
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.
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Development, Quantification, Method Validation and Stability Study of a Novel Fucoxanthin-Fortified Milk
Article
  • Jul 2016
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.
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