Journal of Functional Foods 49 (2018) 73–84

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Journal of Functional Foods

journal homepage: www.elsevier.com/locate/jff

Bioactive compounds and biological functions of sea cucumbers as potential T

functional foods
⁎
Cheng Xua, Rui Zhanga, Zhiyou Wenb,
a
Contemporary Marine Biotechnology (Shenzhen) Co., Ltd., Shenzhen 518000, China
b
Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011, USA

A R T I C LE I N FO A B S T R A C T

Keywords: Sea cucumbers are a group of economically important invertebrate marine animals that have been widely used
Sea cucumbers as tonic foods in Asia countries. Various bioactive compounds in sea cucumbers including peptides, triterpene
Biological function glycosides, polysaccharides, phenols, and lipids have been reported. These compounds demonstrate a myriad of
Bioactive compounds salubrious biological functions such as anti-oxidant, anticancer, anti-inflammation, anti-thrombus, anti-mi-
Nutraceuticals
crobes, anti-diabetes, anti-obesity, and learning and memory improvement. This review is to provide a com-
Markets
prehensive and most recent update of these biological functions and their associated bioactive compounds. The
management practice to keep sustainable sea cucumbers including natural stock fishery and aquaculture were
discussed. The extraction and purification of the bioactive compounds were also summarized, providing a
perspective of preparing sea cucumber derived nutraceuticals. It is expected that this review can provide aca-
demia and industry an insight of sea cucumbers and their potentials in the development of high value nu-
traceutical products.

1. Introduction such as peptides (Zhou, Wang, & Jiang, 2012), triterpene glycosides
(Silchenko et al., 2017), fucoidan (Hu et al., 2015), fucosylated chon-
Sea cucumbers are cucumber-shaped marine invertebrates in the droitin sulfate (Myron, Siddiquee, & Azad, 2014), cerebrosides (Xu
class Holothuroidea. There are more than 1,100 varieties of sea cu- et al., 2011), sphingoid (Tian, et al., 2016) and phenols (Esmat, Said,
cumbers in the world, among which about 40 species are available in Soliman, El-Masry, & Badiea, 2013). As a result, sea cucumbers have
commercial markets (Conand, 2006). Sea cucumbers are popular tonic been reported to possess various biological functions such as anti-oxi-
foods in many Asian countries. Increasing demand has led to an over dative activity (Wang et al., 2012), anticancer (Tian et al., 2005), anti-
exploitation and depletion of the natural stock of sea cucumbers inflammation (Song, Park, Cho, & Park, 2013), antithrombotic activity
(Purcell et al., 2013). Improved aquaculture production and appro- (Matsuhiro, Osorio-Román, & Torres, 2012), anti-diabetes (Barky et al.,
priate natural stock management practices are needed to maintain a 2016), anti-obesity (Tian et al., 2016), and antimicrobial activity
sustainable supply of sea cucumbers. (Pringgenies, 2013).
Sea cucumbers are commonly characterized by high protein and low Many reviews have been published on specific biological functions
lipid contents (Wen, Hu, & Fan, 2010), with a diverse other compounds and related bioactive compounds in sea cucumbers. For example, Xue

Abbreviations: 8-OHdG, 8-oxo-7,8-dihydro-20-deoxyguanosine; 8-oxo-G, 8-hydroxy-20-deoxyguanosine; AAPH, 2,2′-azobis-2-methyl-propanimidamide, dihy-

drochloride; Ach, Acetyl choline; AchE, Acetylcholinesterase; CAT, Catalase; C/EBPα, CCAAT/enhancer binding protein-α; CNS, Central nervous system; DAPCI-MS,
Desorption Atmospheric Pressure Chemical Ionization Mass Spectrometry; DHA, Docosahexaenoic acid; DNA, Deoxyribonucleic acid; DPPH, 1,1-diphenyl-2-pi-
crylhydrazyl; DRIFTS, Diffuse Reflectance mid-Infrared Fourier Transform Spectroscopy; EPA, Eicosapentaenoic acid; FAS, Fatty acid synthase; GPAT, glycerol-3-
phosphate acyltransferase; GR, Glutathione reductase; GSH-px, Glutathione peroxidase; iNOS, Inducible nitric oxide synthase; MAPKs, Mitogen-activated protein
kinase; MDA, Malondialdehyde; MMP-2, Matrix metalloproteinase-2; MMP-9, Matrix metalloproteinase-9; NADPH, Nicotinamide adenine dinucleotide phosphate;
NO, Nitric oxide; p85-PI3K, p85- phosphoinositide 3-kinase; p-ERKs, p-Extracellular signal–regulated kinases; p-JNKs, p-Jun N-terminal kinases; PI3K/PKB, phos-
phoinositide 3-kinase/ protein kinase B; PPARγ, Peroxisome proliferator-activated receptor-γ; ROS, Radical oxygen species; Ser473-PKB, Ser473-protein kinase B; SI-
FA, Stable Isotope and Fatty Acid; SOD, Superoxide Dismutase; SREBP-1c, Sterol regulatory element‐binding protein1c; Thr308-PKB, Thr308- protein kinase B; TNF-
α, Tumor necrosis factor alpha; UV, Ultraviolet
⁎
Corresponding author at: 2312 Food Science Building, 536 Farm House Ln, Department of Food Science and Human Nutrition, Iowa State University, Ames, IA
50011, USA.
E-mail address: wenz@iastate.edu (Z. Wen).

https://doi.org/10.1016/j.jff.2018.08.009
Received 3 May 2018; Received in revised form 3 August 2018; Accepted 6 August 2018
1756-4646/ © 2018 Elsevier Ltd. All rights reserved.
C. Xu et al. Journal of Functional Foods 49 (2018) 73–84

et al. (2015) reported the functional characterization and mechanism of analysis, cluster analysis, and discriminant analysis, these chemical
the immune-related molecules. Triterpene glycosides have been widely analytical methods proved high differentiating accuracy.
studied for their anticancer characteristics (Adrian & Collin, 2018;
Aminin et al., 2015; Janakiram, Mohammed, & Rao, 2015; Wargasetia
& Widodo, 2017) and other broader biological activities (Bahrami & 3. Active compounds in sea cucumbers
Franco, 2016). The biological and taxonomic perspectives (Honey-
Escandón, Arreguín-Espinosa, Solís-Marín, & Samyn, 2015) and struc- 3.1. Overall chemical compositions of sea cucumbers
ture and function relationships (Park, Bae, Kim, Stonik, & Kwak, 2014)
of these special group of compounds were also reported. Another im- Sea cucumbers have long been regarded as a tonic food in Asian
portant compound in sea cucumbers, polysaccharide fucosylated countries. Proteins are the most abundant chemical components and
chondroitin sulfate, was also reviewed (Myron, Siddiquee, & Al Azad, can account 40 ∼ 60 wt% of sea cucumber dry matter (Wen et al.,
2014; Pomin, 2014). 2010). Most sea cucumber proteins are in the form of collagen with up
Although many reviews about sea cucumbers have been reported, to 70 wt% of body wall proteins being insoluble collagen fiber (Saito,
most reviews were focusing on specific groups of compounds and their Kunisaki, Urano, & Kimura, 2002). Glutamic acid (Bechtel, Oliveira,
associated biological functions. From an application point of view, re- Demir, & Smiley, 2013; Roggatz et al., 2017; Zhong, Khan, & Shahidi,
ports on the use of sea cucumbers as functional foods and drug products 2007) and glycine (Saito et al., 2002; Wen et al., 2010) are two
are still limited. There is also a lack of summary of the most recent dominant amino acids in sea cucumber proteins.
discoveries of sea cucumbers biological functions such as anti-diabetes, Fatty acids in sea cucumbers exist at a relatively small amount.
anti-obesity and improvement of learning and memory (Bordbar, Total fatty acids account for 2 ∼ 8 wt% in sea cucumber dry matter,
Anwar, & Saari, 2011, Kiew & Don, 2012). Reviews of the extraction among which unsaturated fatty acids can account for up to 70%.
and purification of active compounds from sea cucumbers have been Eicosapentaenoic acid (EPA, C20:5, n-3) in total fatty acids can be up to
scarce. Additionally, reviews of the management practices to maintain a 56.7%, while the content docosahexaenoic acid (DHA, C22:6, n-3) was
sustainable sea cucumber supply have been largely neglected. much lower (up to 5.8% of total fatty acids) (Bechtel et al., 2013; Gao
The aim of this review is to address the above shortcomings by et al., 2016; Salarzadeh et al., 2012; Zhong et al., 2007). Sea cucumbers
providing an update of the most recent discoveries of sea cucumber contain around 15 wt% carbohydrate in body wall and 8 wt% in muscle
biological functions and the associated bioactive compounds. bands (Bechtel et al., 2013). In addition to these three major compo-
Considering the potential of developing sea cucumber-based nu- nents, sea cucumbers are also rich in elements such as Ca, Mg, Fe, with
traceuticals and pharmaceuticals, the practices of preparing pure contents varying among different species (Barzkar, Fariman, & Taheri,
bioactive compounds and maintaining a sustainable sea cucumber 2017; Lee et al., 2014; Wen & Hu, 2010).
sources were discussed. The information will provide a comprehensive
perspective on developing sea cucumber based nutraceuticals. 3.2. Collagens

2. Classification and identification of sea cucumbers Collagens as main structural proteins build sea cucumber body tis-
sues and contribute sea cucumbers’ palatable tastes (Liu, Zamora, Jeffs,
Sea cucumbers are soft-bodied marine animals that can be found on & Quek, 2017). Collagens in sea cucumbers commonly consist of three
the seabed all around the world (Conand, 2006). More than 1,100 sea polypeptide chains, each of which contains a repeating Glycine-X-Y
cucumber varieties have been reported among which the families Ho- motif where X and Y represent any amino acids (Hulmes, 2008). As a
lothuridae, Stichopodidae, and Cucumariidae are most valuable for com- result, glycine is the most abundant amino acid in sea cucumber col-
mercial markets. Sea cucumbers originated from different locations lagen (Abedin et al., 2014; Adibzadeh, Aminzadeh, Jamili, Karkhane, &
may differ in their food and medical values, it is therefore important to Farrokhi, 2014; Lin et al., 2017; Liu et al., 2017; Zhong, Chen, Hu, &
specify their origins. Ren, 2015).
Sea cucumber species can be identified through their genetic char- Collagen fibers are formed by covalent cross-links between col-
acteristics such as microsatellite (Kang et al., 2011; Kanno, Suyama, Li, lagens. Electrophoretic assay revealed that sea cucumber fiber tissues
& Kijima, 2006; Kim, Choi, & An, 2008). Microsatellite analysis is based are thin, uniform and densely interwoven collagenous fibrils (Liu et al.,
on the fact that polymorphic DNA loci (microsatellite markers) contain 2017). External factors such as temperature, salt concentration, sun-
repeated nucleotide sequences and do not change among the same light exposure, and nutrient deficiency can induce autolysis of sea cu-
species. Once the microsatellite-based markers are developed, the gene cumber body walls, and drastically change of the tissues mechanical
differentiation between sea cucumber populations can be verified, properties such as contraction, relaxation and mucoid degeneration
which can be further used to identify the species. (Liu et al., 2018).
Characterization of special compounds can also be used to identify
sea cucumbers. For example, triterpenoid glycosides were commonly
used to identify species based on their species-specific structures 3.3. Glycosides
(Honey-Escandón et al., 2015). With the advancement of chemical
analytical methods, more and more special compounds in sea cu- Glycosides are molecules in which a sugar is bound to another
cumbers can be characterized to identify the geographical locations and functional group via a glycosidic bond. Sea cucumbers contain tri-
origins of sea cucumbers. For example, special pigments and proteins terpene glycosides as abundant secondary metabolites. The unique
located on sea cucumber body surface can be determined through structure of triterpene glycosides contribute to their biological activity
Desorption Atmospheric Pressure Chemical Ionization Mass Spectro- and can be used as taxonomic markers (Honey-Escandón et al., 2015;
metry (DAPCI-MS) (Wu, et al., 2009). The unique mid-infrared spec- Kalinin, Avilov, Silchenko, & Stonik, 2015). The carbohydrate chains of
troscopy fingerprints of sea cucumbers can be analyzed through Diffuse triterpene glycosides commonly contain xylose, glucose, quinovose, 3-
Reflectance mid-Infrared Fourier Transform Spectroscopy (DRIFTS) O-methylglucose, and in rare cases, 3-O-methylxylose, 3-O-methylglu-
(Wu, et al., 2010). Stable Isotope and Fatty Acid (SI-FA) analysis ac- curonic acid, 3-O-methylquinovose, and 6-O-acetyl-glucose (Kalinin
cesses sea cucumbers based on their δ13C and δ15N and fatty acid et al., 2015; Kalinin, Silchenko, Avilov, Stonik, & Smirnov, 2005).
profiles (Zhang, Liu, Li, & Zhao, 2017). Multi-elements analysis was Holostane type triterpene glycosides (lanostane derivatives with an
used to analyze sea cucumber elements profiles (Liu, Xue, et al., 2012). 18(20)-lactone) is the most common triterpene glycosides found in sea
With the appropriate data analyses such as principal components cucumbers.

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3.4. Polysaccharides chelating activity (Ghanbari et al., 2015). A low molecular weight of
antioxidant peptide contained 46.7% hydrophobic amino acids with a
Sea cucumbers contain a various polysaccharides such as fucoidan, sequence of GPEPTGPTGAPQWLR (Zhou et al., 2012). Zheng et al.
fucosylated chondroitin sulfate, and fucan. The backbone of fucoidan is (2012) reported three sea cucumber antioxidant peptides, VTPT, VLLT,
built by (1–3)-linked tetrafucose repeated unit, with each fucose unit and VGTVGM, contained 50%, 75%, and 50% hydrophobic amino
having one or two HSO4 substitution on its cyclic structure (Chang acids, respectively.
et al., 2016; Hu et al., 2015; Yu et al., 2014, 2013; Yu, Xue, et al., Polysaccharides in sea cucumbers also have anti-oxidative activities.
2014). Fucosylated chondroitin sulfate (FucCS) has chondroitin sulfate Polysaccharides prepared from Apostichopus japonicas demonstrated a
type backbone with sulfated or non-sulfated fucose attached on side free radicals scavenging ability and reducing power; the poly-
chain (Myron et al., 2014). Some studies reported that fucan consists of saccharides had molecular weight of 36.2 kDa, with main composition
1 → 3 and/or 1 → 2 linked tetrasaccharide repeating units with sulfated of glucosamine, galactosamine, glucuronic acid, mannose, glucose,
or non-sulfated fucose residues attached to its backbone chain (Cao, galactose and fucose (Liu et al., 2012). Sea cucumber fucoidan with a
Surayot, & You, 2017; Chen et al., 2012; Wu et al., 2015). molecular weight of 1614.1 kDa suppressed the expression of p-JNKs
The complex structures of polysaccharides are responsible for their and p-ERKs, two enzymes regulating the MAPKs pathway in response to
biological functions. For example, Mulloy, Mourao, and Gray (2000) oxidative stress (Wang et al., 2012). Fucosylated chondroitin sulfate
reported that sulfated fucose branches in fucosylated chondroitin sul- derived from two sea cucumber species (A. molpadioidea and H. nobilis)
phate were crucial in exerting anticoagulant activity of sea cucumbers. also exhibited a moderate antioxidant activity (Zou et al., 2016).
Trisaccharide units with 2,4-O-disulfated fucose branches in fucosy- In addition to protein and polysaccharides, other compositions in
lated chondroitin sulphate played a critical role to facilitate neurite sea cucumbers such as polyphenols (Husni, Shin, You, & Chung, 2009;
outgrowth (Shida, Mikami, Tamura, & Kitagawa, 2017). Fucosylated Scalbert, Johnson, & Saltmarsh, 2005), flavonoids (Mamelona et al.,
chondroitin sulphate and fucoidan with linear chains exhibited a more 2007), phospholipids and cerebrosides (Wu et al., 2014, 2013, 2012)
potent of antihyperlipidemic activity than random chains (Li, Li, Zhi, also exhibited anti-oxidative activities. Coelomic fluid collected from
Wei, et al., 2017). In another study, Li, Li, Zhi, Hu, et al., (2017) re- sea cucumbers contains SOD, CAT and GR with high potent activities
ported that different sulfation patterns in fucoidan accounted for sea (Dolmatova, Eliseikina, & Romashina, 2004).
cucumbers anti-hyperlipidemic activities.
4.2. Anti-cancer activities
3.5. Phenols
A recent phase II clinical trial showed the effectiveness anti-cancer
Sea cucumbers are also good sources of phenols which play an of sea cucumber extract in vivo (Chari et al., 2018). In general, some
important role in antioxidant activity. The compositions of sea cu- compounds in sea cucumbers can be potentially used as anticancer
cumbers phenols are different from those derived in fruits and vege- products. For example, cerebrosides induce tumor cell apoptosis
tables. Chlorogenic acid (up to 93 wt%) is the major phenolic compo- through the mitochondria pathway (Du et al., 2012; Sugawara et al.,
nents in sea cucumbers while the content of ascorbic acid was very 2006). The extract of H. parva induced death of chronic lymphocytic
minimal (Esmat et al., 2013; Fahmy 2015). Other phenols such as leukemia through mitochondria pathway without harming the healthy
pyrogallol, rutin, coumaric acid, and catechin were also detected in sea B-lymphocytes (Salimi et al., 2017). Extracts from sea cucumbers also
cucumbers (Dakrory et al., 2015; Esmat et al., 2013; Fahmy, 2015). The demonstrated curative effects on skin-cancer (Kim et al., 2017).
phenols contents in different tissues of the sea cucumbers also vary A sulfated saponin extracted from the sea cucumber Pentacta
widely (Mamelona et al., 2007). quadrangularis was observed an anti-angiogenesis effect through in-
hibiting the receptor of vascular endothelial growth factor (Tian et al.,
4. Biological functions of sea cucumbers 2005). The anti-cancer activity of sulfated saponin compounds was
further reported through suppressing the interaction between kinase
Various biological functions in sea cucumbers have been reported. insert domain containing receptor and αvβ3 integrin (Tian et al., 2007).
Those functions are often species-specific and closely associated with Silchenko et al. (2017) reported that triterpene glycosides from the sea
the bioactive compounds contained in sea cucumbers. A list of biolo- cucumber Neothyonidium magnum exhibited not only a cytotoxic effect
gical functions and their bioactive compounds in related sea cucumber on DLD-1 cells but also a synergism with anti-proliferative effect of
species are summarized in Table 1 and explained below. radioactive irradiation.
Metastasis is one hallmark of cancers with the possibility of curative
4.1. Anti-oxidative activities treatment for cancer patients being reduced significantly once metas-
tasis happens. Selectins interact with certain glycoproteins in cancer
Radical oxygen species (ROS) generated from various sources (mi- cells and facilitate the development of cancer cells metastasis.
tochondria, peroxisomes, NADPH oxidase, cytokines, UV radiation, Fucosylated chondroitin sulfate extracted from the sea cucumber L.
chemotherapeutic agents, and hyperthermia) can cause oxidative stress grisea can effectively block the interaction between selectin and tumor
and disturb human body physiological functions such as protein cells and inhibit the metastasis (Borsig et al., 2007). The mechanism
structure modification, DNA damages, deviant cellular signaling, de- was due to the binding of fucosylated chondroitin sulfate to selectin
creased proliferative response, and defective host defenses (Finkel & prior to tumor cells development (Borsig et al., 2007). Triterpene gly-
Holbrook, 2000). Sea cucumbers exert strong capability of scavenging coside derived sea cucumbers also showed the anti-metastatic activity
ROS. For example, the fresh and rehydrated sea cucumber Stichopus (Zhao et al., 2011).
japonicus was reported to scavenge AAPH and DPPH radicals (Zhong
et al., 2007), while the organic/aqueous extract of Holothuria atra de- 4.3. Anti-inflammation activities
monstrated Fe+ chelating activity and lipid peroxidation repressing
capability (Dakrory et al., 2015; Esmat et al., 2013). Inflammation is a human reaction to harmful stimuli such as pa-
Protein hydrolysates from sea cucumbers exhibit anti-oxidant ac- thogens and damaged cells. Appropriate inflammation reaction resists
tivities depending on molecular weight, amino acids composition and the invasion of external pathogens and clears out or repairs the da-
peptide hydrophobicity (Zou, He, Li, Tang, & Xia, 2016). Peptides-rich maged cells. However, persisting and overreacted inflammation can
enzymatic hydrolysates from the sea cucumber Actinopyga lecanora cause damage to human body and lead to cancers. Studies have shown
scavenged the DPPH radicals and showed a great Ferrous ion (Fe+) that sea cucumber extracts contain effective anti-inflammation

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Table 1
Bioactive compounds of sea cucumber, its sources and health functions.
Health functions Species Bioactive compounds

Anti-oxidative activity Cucumaria frondosa Organic extracts (Zhong et al., 2007); flavonoids (Mamelona et al., 2007); phospholipids (Wu et al., 2014)
Holothuria atra Organic/aqueous extracts (Dakrory et al., 2015; Esmat et al., 2013)
Actinopyga lecanora Enzymatic hydrolysates (Ghanbari et al., 2015)
Stichopus Japonicus Peptide (Zhou et al., 2012; Liu et al., 2012), polyphenols (Husni et al., 2009)
Apostichopus japonicas Polysaccharides (Zou et al., 2016)
Acaudina molpadioides Fucoidan (Wang et al., 2012); fucosylated chondroitin sulfate (Scalbert et al., 2005); cerebrosides (Wu et al.,
2013)
Eupentacta fraudatrix Coelomic fluid (Dolmatova et al., 2004)
Anticancer Acaudina molpadioides Cerebrosides (Du et al., 2012)
Stichopus variegates Cerebrosides (Sugawara et al., 2006)
Holothuria parva Organic extract (Salimi et al., 2017)
Apostichopus japonicus Extracts (Kim et al., 2017)
Pentacta quadrangularis Sulfated saponin (Tian et al., 2005, 2007)
Neothyonidium magnum Triterpene glycosides (Silchenko et al., 2017)
Ludwigothurea grisea Fucosylated chondroitin sulfate (Borsig et al., 2007)
Pearsonothuria graeffei Triterpene glycoside (Zhao et al., 2011)
Anti-inflammation activity Stichopus japonicus Organic extract (Himaya et al., 2010; Lee et al., 2016; Song et al., 2013); sulfated polysaccharide (Cui et al.,
2016)
Isostichopus badionotus Fucoidan (Wang et al., 2016)
Cusumaria frondosa Fucosylated chondroitin sulphate (Li et al., 2015)
Holothuria forskali Enzymatic hydrolysates (Li et al., 2015)
Parastichopus tremulus Enzymatic hydrolysates (Li et al., 2015)
Anti-thrombotic activities Acaudina molpadioidea Fucosylated polysaccharide sulfate (Ye et al., 2012)
Athyonidium chilensis Sulfated polysaccharide (Matsuhiro et al., 2012)
Holothuria mexicana Fucosylated polysaccharide sulfate (Mou et al., 2017)
Isostichopus badionotus Fucan (Chen et al., 2012); fucosylated chondroitin sulfate (Li et al., 2017)
Thelenata ananas Fucosylated chondroitin sulphate (Wu et al., 2010)
Pearsonothuria graeffei Fucosylated chondroitin sulfate (Li et al., 2017)
Apostichopus japonicas Polysaccharides (Luo et al., 2013)
Holothuria edulis Polysaccharides (Luo et al., 2013)
Holothuria nobilis Polysaccharides (Luo et al., 2013)
Holothuria polii Fucosylated chondroitin sulphate (Mansour et al., 2017)
Anti-diabetic activities Acaudina molpadioides Fucoidan (Hu, Xia, et al., 2014); fucosylated chondroitin sulfate (Hu et al., 2014); peptide (Li et al., 2017)
Cucumaria frondosa Fucosylated chondroitin sulfate (Hu, Chang, et al., 2014); phosphatidylcholine (Hu, Xu, et al., 2014)
Holothuria thomasi Saponin (Barky, et al., 2016)
Stichopus japonicas Fatty acids (Nguyen & Kim, 2015)
Anti-obesity activities Cucumaria frondosa Phospholipid (Liu, et al., 2014; Tian, et al., 2016); cerebrosides (Xu, Wang, et al., 2015a, 2015b)
Acaudina molpadioides Cerebrosides (Liu, et al., 2015); fucoidan (Xu, et al., 2014); fucosylated chondroitin sulfate (Xu, Wang, et al.,
2015a, 2015b)
/ Phospholipid (Vaidya & Cheema, 2014)
Apostichopus japonicas Vanadium (Liu et al., 2015)
Anti-microbial activities Bohadschia mamorata Extract (Pringgenies, 2013)
Bohadschia argus Extract (Pringgenies, 2013)
Holothuria parva Organic extract (Mashjoor & Yousefzadi, 2017)
Stichopus variegatus Organic extract (Shakouri et al., 2017)
Holothuria tubulosa Peptide (Schillaci et al., 2013)
Holothuria (Microthele) axiloga Triterpene glycosides (Yuan et al., 2008)
Holothuria scabra Lectin (Gowda, Goswami, & Islam Khan, 2008)
Anti-fatigue Stichopus japonicus Peptide (Ye et al., 2017)
ACE inhibitory Actinopyga lecanora Enzymatic hydrolysates (Ghanbari et al., 2015; Sadegh Vishkaei, Ebrahimpour, Abdul-Hamid, Ismail, & Saari,
2016)
Improving learning/memory Cucumaria frondosa Phospholipids (Wu et al., 2014)
Acaudina molpadioides Cerebrosides (Che et al., 2017); phosphatidylcholine (Zhou et al., 2016)
Anti-hyperlipidemic activity Apostichopus japonicus Polysaccharides (Zou et al., 2016)
Pearsonothuria graeffei Fucosylated chondroitin sulfate (Li et al., 2017)
Isostichopus badionotus Fucosylated chondroitin sulfate (Li et al., 2017)
Pearsonothuria graeffei Fucoidan (Li et al., 2017)
Metriatyla scabra Glycosaminoglycans (Liu et al., 2002)
Hepatoprotective activity Holothuria atra Phenolic extract (Esmat et al., 2013)

compounds (Himaya, Ryu, Qian, & Kim, 2010; Lee et al., 2016; Song epicardial adipose tissue (Mena-Bueno et al., 2016).
et al., 2013).
Injury of central nervous system (CNS) often accompanies with in-
flammation. Sulfated polysaccharide isolated from the sea cucumber 4.4. Anti-thrombotic activities
Stichopus japonicas alleviated the CNS injury by recruiting neural stem
cells to the injury site and increasing MMP-2, MMP-9, and iNOS protein Thrombus is an excessive response of human body to injury and
levels (Cui et al., 2016). Fucoidan and fucosylated chondroitin sulphate often results in a clot and obstructs blood flow. Drugs are commonly
were reported capable of regulating inflammatory cytokines in vivo (Li used to cure thrombus through three mechanisms, obstructing platelet
et al., 2015; Wang et al., 2016). The extracts from two sea cucumbers aggregation; prolonging the clotting formation; and dissolving the clots.
Holothuria forskali and Parastichopus tremulus exerted anti-inflammation Fucosylated chondroitin sulfate and sulfated fucan in sea cucumbers
activity on endothelial cells and subcutaneous adipose tissue, but not on have demonstrated anti-coagulant and anti-thrombotic activities
(Matsuhiro et al., 2012; Mou, Wang, Li, & Yang, 2017; Ye, Xu, & Li,

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2012). A fucan compound isolated from sea cucumbers has high anti- curing diabetes by sea cucumbers. The bioactive compounds in sea
thrombotic activity and was used to treat thrombosis with decreased cucumbers and their anti-diabetics mechanisms are summarized in
bleeding risk (Chen et al., 2012). A fucosylated chondroitin sulphate Fig. 1. As α-glucosidase plays an important role in diabetes, inhibition
compound exhibited a similar effect (Wu, Xu, Zhao, et al., 2010). The of α-glucosidase can be an effective method to treat diabetes (Upadhyay
anti-thrombotic activity of sea cucumber polysaccharides is closely re- et al., 2017). A study found that sea cucumbers fatty acids exerted anti-
lated with their structures such as monomer composition, sulfate con- hyperglycemic activity by inhibiting α-glucosidase activity (Nguyen &
tent, molecular size, and sulfated patterns (Li, Li, Yan, et al., 2017; Luo Kim, 2015). Fucoidan isolated from the productive sea cucumber A.
et al., 2013). For example, fucosylated chondroitin sulphate demon- molpadioides was capable of down-regulating serum resistin, leptin and
strated an unusual pro-coagulant activity that is closely related with TNF-α and increasing hepatic glycogen (Hu, Xia, et al., 2014). Fuco-
charge density, sugar composition and molecular mass (Mansour et al., sylated chondroitin sulfate can improve insulin sensitivity and glucose
2017). However, when it goes through the gastrointestinal tract after metabolism through regulating the key genes for phosphorylation, such
oral administration, biological functions of fucosylated chondroitin as p85-PI3K, Ser473-PKB, and Thr308-PKB in PI3K/PKB pathways (Hu,
sulphate can be negatively influenced by gastrointestinal tract before it Chang, et al., 2014; Hu et al., 2014). The anti-diabetic activity of EPA-
is absorbed by body. Gastro-resistant tablet formulation is a successful rich phosphatidylcholine derived from sea cucumbers was reported
solution to avoid this degradation (Fonseca, Sucupira, Oliveira, Santos, through decreasing blood glucose level, augmenting serum insulin and
& Mourão, 2017). glycogen contents by regulating PI3K/PKB pathways (Hu, Xu, et al.,
2014). Numerous studies indicate saponins in sea cucumbers can po-
4.5. Anti-microbial activities tentially treat diabetes through increasing serum insulin and glycogen
levels (Barky et al., 2016). In addition to saponins, some polypeptides
Sea cucumbers can be an important resource for anti-microbial in sea cucumbers also exhibited anti-hyperglycemic activity (Li, Xu, &
compounds, depending on the species, tissues, and solvents used for the Su, 2017).
compounds extraction (Pringgenies, 2013). Two sea cucumber organs
isolated with ethyl acetate and methanol exhibited antimicrobial ac- 4.7. Anti-obesity activities
tivities (Mashjoor & Yousefzadi, 2017). In another study, the aqueous
methanol extract from sea cucumber body wall showed the best anti- In general, bioactive compounds treat obesity commonly through
microbial activity (Shakouri, Shoushizadeh, & Nematpour, 2017). The the following mechanisms: (1) appetite control, (2) blocking fat ab-
different sea cucumber anti-microbial activities were due to the dif- sorption, (3) stimulating energy, (4) suppressing adipose tissue growth,
ferent living environments and unique chemical substances such as and (5) increasing body fat mobilization (Hu, Tao, et al., 2016). The
peptides (Schillaci et al., 2013), triterpene glycosides (Yuan, Yi, Xue, anti-obesity activities have been reported for various sea cucumbers
Zhang, & La, 2008), and lectin (Gowda, Goswami, & Khan, 2008). compounds through alleviating metabolic syndrome (Fig. 2). A fu-
coidan compound isolated from the sea cucumber Acaudina molpa-
4.6. Anti-diabetic activities dioides significantly decrease fat content in vitro (Xu et al., 2014). Fu-
cosylated chondroitin sulfate obtained from the sea cucumber Acaudina
Diabetes is caused by dysfunctional interaction between insulin molpadioides can inhibit adipose (fat) tissue growth (Xu, Wang, et al.,
resistance and insulin secretion, resulting in hyperglycemia and leading 2015a, 2015b). The anti-obesity mechanisms of fucoidan and fucosy-
to damage of different organs in human body (Upadhyay et al., 2017). lated chondroitin sulfate are similar, i.e., activating the Wnt/β-catenin
Most recent studies have demonstrated the activities of treating and pathway which negatively influences on adipocyte differentiation;

Fig. 1. Sea cucumber active compounds and their anti-diabetes mechanisms. Abbreviations: G6Pase: Glucose-6-phosphatase; GLUT4: Glucose transporter 4; GP:
Glycogen phosphorylase; HK: Hexokinase; IR: Insulin receptor; IRS-1: Insulin receptor substrate 1; IL6: Interleukin-6; PK: Pyruvate kinase; PKB: Protein kinase B;
PI3K: Phosphatidylinositol 3-hydroxy kinase; TNF-a: Tumor necrosis factor alpha; Tyr: Tyrosine.

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C. Xu et al. Journal of Functional Foods 49 (2018) 73–84

Fig. 2. Sea cucumber active compounds and their anti-obesity mechanisms. Abbreviations: ATGL: Adipose triglyceride lipase; C/EBPa: CCAAT/enhancer binding
protein-a; FAS: Fatty acid synthase; FZ: Frizzled receptor; FZ1: Frizzled receptor1; G6PDH: Glucose 6-phosphate dehydrogenase; HSL: Hormonesensitive lipase; LPL:
Lipoprotein lipase; LRP5: Lipoprotein receptorrelated protein 5; ME: Malic enzyme; PPARγ: Peroxisome proliferator-activated receptor-γ; SREBP-1: Sterol regulatory
element-binding protein1; TG: Triacylglycerol.

down-regulates the expression of SREBP-1c, C/EBPα and PPARγ; and showed sea cucumber extract significantly alleviated degeneration of
oppresses two key enzymes fatty acid synthase (FAS) and glycerol-3- liver cell and regression of liver fibrosis and necrosis (Esmat et al.,
phosphate acyltransferase (GPAT) in fat tissue growth. Phospholipid 2013). A recent study showed that sea cucumber peptides with small
(Liu et al., 2014, 2015; Tian et al., 2016; Vaidya & Cheema, 2014) and molecular weight alleviated the fatigue (Ye, Shen, Huang, Zhang, &
cerebroside (Liu et al., 2015) in sea cucumbers have also exhibited anti- Xiao, 2017). Polysaccharides such as glycosaminoglycans and fucan are
obesity activities. At cellular level, Wnt/β catenin pathway also plays potent anti-hyperlipidemic compounds (Li et al., 2017; Liu, Fau, Hu, &
an important role in anti-obesity effect of cerebrosides. For example, M.-L., & Hu, M. L. , 2002; Liu et al., 2012). Diets containing the sea
cerebrosides from the sea cucumber Cucumaria frondosa suppressed cucumber Isostichopus badionotus inhibited high cholesterol through the
adipogenic transcription factors involved in Wnt/β-catenin pathway induction of key genes related to cholesterol and lipid metabolism
(Xu, Wang, et al., 2015a, 2015b). Vanadium purified from the sea cu- (Olivera-Castillo et al., 2013). Sea cucumber peptides can also inhibit
cumber Apostichopus japonicas inhibited adipocytes differentiation angiotensin-I converting enzyme for treating hypertension (Ghanbari,
through activating Wnt/β-catenin pathway (Liu, Xu, Xue, et al., 2015). et al., 2015; Sadegh Vishkaei et al., 2016).

4.8. Improving learning and memory 5. Sea cucumber sources

Recent studies also reported the improvement of learning and 5.1. Natural stock fishery
memory capabilities of sea cucumbers. Fig. 3 shows the mechanisms of
improving learning and memory for sea cucumber derived bioactive Traditionally, sea cucumbers have been mainly obtained through
compounds. Fatty acids in sea cucumber can effectively improve im- natural catching and fishery. Worldwide, sea cucumbers are produced
paired learning and memory functions related to aging and neuro-de- and exported from several regions such as Asian Pacific (Indonesia, the
generative diseases (Che, et al., 2017; Wu et al., 2014; Zhou et al., Philippines, Singapore, Malaysia, Papua New Guinea, Solomon Islands,
2016). Phosphatidylcholine from sea cucumber can inhibit the activity Fiji and Australia), Middle East (United Arab Emirates, Yemen) and
of AchE, which attacks AcH, an important neurotransmitter in learning some African countries (Mozambique, Kenya, Madagascar and South
and memory (Zhou et al., 2016). Cerebrosides, a group of complex li- Africa) (Ferdouse, 2004). However, the over-exploitation and depletion
pids, improved the cognitive performances of mice by decreasing the of natural sea cucumber stocks has been a serious concern, particularly
content of MDA, 8-OHdG, 8-oxo-G, and NO, and facilitating the activity in Asian Pacific region (Purcell et al., 2013). In order to maintain a
of SOD; cellular study found that cerebrosides inhibited the cell apop- healthy and sustainable sea cucumber source, appropriate management
tosis by regulating the expression of apoptosis-related proteins, such as practices such as limited harvesting, setting up catching quotas, and
Bax, Caspase-9, cleaved Caspase-3, and Bcl-2 (Che et al., 2017). Phos- rotational harvesting (Purcell, Lovatelli, & Pakoa, 2014; Purcell et al.,
pholipids in sea cucumbers also showed similar effects by exerting 2013) need to be implemented.
antioxidant effects and inhibiting cell apoptosis (Wu et al., 2014). Limited harvesting is usually achieved by shortening fishing seasons
and/or setting specific number or species allowed to be harvested
4.9. Other bioactivities (Purcell, Polidoro, Hamel, Gamboa, & Mercier, 2014). In order to plan
an appropriate fishing season, sea cucumber stock in a specific area
Sea cucumbers also exhibit a variety of other biological activities. must be carefully monitored. Wolff, Schuhbauer, and Castrejón (2012)
For example, phenolic compounds extracted from in sea cucumbers can reported a method to estimate sea cucumber stocks based on macro-
normalize biological indexes (serum direct bilirubin, alanine, aspartate zone differences in density and distribution. Prescott et al. (2013) re-
aminotransferases, hepatic malondialdehyde, hydroxyproline con- ported a method to estimate sea cucumber abundance and exploitation
centrations and antioxidant enzyme activities). Histologic results rates by continually removing animals in specific area. A passive

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C. Xu et al. Journal of Functional Foods 49 (2018) 73–84

Fig. 3. Sea cucumber active compounds and

their improving learning and memory mechan-
isms. Abbreviations: 8-OHdG: 8-oxo-7,8-di-
hydro-20-deoxyguanosine; 8-oxo-G: 8-hydroxy-
20-deoxyguanosine; Ach: Acetyl choline; AchE:
Acetylcholinesterase; MAO: Monoamine oxidase;
MDA: Malondialdehyde; NO: Nitric oxide; SOD:
Superoxide dismutase.

integrated transponder tagged onto sea cucumber was used to monitor aquatic animals used in co-culturing with sea cucumbers can be fish,
specific species (Gianasi, Verkaik, Hamel, & Mercier, 2015). Rotational shrimp and green-lipped mussel. Sea cucumber co-cultured under fish
harvesting is another practice commonly used to improve biological cage can avoid predators, adverse environmental conditions, and obtain
and economic performance of aquatic animals (Plagányi, Skewes, food supply from fish cage (Yokoyama, 2013). When co-cultured with
Murphy, Pascual, & Fischer, 2015). However, a recent study revealed shrimp or mussel, sediments and fecal produced by those animals
that sea cucumbers, unlike agricultural crops with more predictable provided nutrients to sea cucumbers (Slater & Carton, 2007; Zhou et al.,
growth, are less robust to grow in a natural environment (Purcell, 2017).
Uthicke, Byrne, & Eriksson, 2015). Therefore, the practice of rotational
harvesting needs to be used cautiously when it is applied to sea cu- 6. Extraction and purification of bioactive compounds in sea
cumbers. cucumbers

5.2. Aquaculture Extraction of bioactive compounds from sea cucumbers often fol-
lows the procedures of pretreatment, extraction and purification. In the
Aquaculture is another approach to produce sea cucumbers but with pretreatment step, sea cucumbers are dried and pulverized into powder.
some challenges. Diseases such as rotting edges, ulceration of the sto- The most common drying methods used are sun drying and freeze-
mach, autolysis of young juveniles, skin ulceration, erosion of epidermis drying. Other drying methods such as microwave drying (Duan, Zhang,
and body oedema can account for up to 80% mortality of cultured sea Mujumdar, & Wang, 2010), ultrasound drying (Duan, Zhang, Li, &
cucumbers (Liu et al., 2010; Wang et al., 2007; Wang, Zhang, Rong, Mujumdar, 2008), electro-hydrodynamic drying (Bai, Qu, Luan, Li, &
Chen, & Shi, 2005). Environmental factors such as water temperature Yang, 2013; Bai, Yang, & Huang, 2012), and infrared radiation drying
and salinity also significantly influence phagocytosis and enzyme ac- (Moon, Kim, Chung, Pan, & Yoon, 2014) were also reported to improve
tivity of sea cucumbers (Wang, Yang, Gao, & Liu, 2008). The optimal sensory characteristics and reduce nutrition loss.
temperature for food intake by sea cucumbers was reported to be After drying, the active compounds in sea cucumbers can be ex-
14 ∼ 15 °C (Yang, et al., 2005). In another study, the optimal tem- tracted. Table 2 summarizes the various methods used for extraction.
perature for larval growth of the sea cucumber Holothuria spinifera was Organic solvent based extraction is commonly used. For example, tri-
28 ∼ 32 °C (Asha & Muthiah, 2005). Temperature fluctuation could terpene glycosides was extracted with refluxing 60% ethanol at
promote sea cucumber larval growth but with a little impact on lipid 70–85 °C (Guo et al., 2015; Hu et al., 2012). Cerebrosides was extracted
content and oxygen consumption (Dong, Dong, Tian, Wang, & Zhang, with CHCl3/MeOH and EtOAc/n-BuOH mixture followed with acetone
2006). Sea cucumber culture also requires balanced nutrients. Protein washing (Xu et al., 2011). As an alternative to organic-solvents, enzy-
content, amino acids constitution, and calcium to phosphorus ratio are matic extraction can also be used to extract sea cucumber active com-
important factors to promote sea cucumber growth (Sun et al., 2004). In pounds. Under appropriate pH, temperature, reaction time, and enzyme
addition to the basic nutrients needs, other nutritional sources such as to substrate ratio, enzymes can target specific sites of proteins to pro-
dietary sea mud and yellow soil (Liu, Dong, Tian, Wang, & Gao, 2009), duce desirable bioactive peptides (Ghanbari et al., 2015) and extract
small periphitic diatoms (Ito & Kitamura, 1997), algae (Yuan et al., polysaccharides (Yu et al., 2013). Recently, supercritical fluid extrac-
2006) and bivalve wastes (Slater, Jeffs, & Carton, 2009; Yuan et al., tion as an environment-friendly technique has been increasingly used in
2006) were also used in sea cucumber culture based on the unique extracting sea cucumbers bioactive compounds (Grosso, Valentão,
characteristics of these ingesting deposit matters. Ferreres, & Andrade, 2015). This method is particularly appealing to
Co-culturing sea cucumber with other aquatic animals was also at- produce high-value nutraceuticals from sea cucumbers.
tempted in order to improve sea cucumbers survival and growth. A co- A purification step is usually following the extraction step to pro-
culture system containing sea cucumbers and juvenile charm abalones duce pure compounds from sea cucumbers (Table 2). For example,
significantly reduced the water nitrogen content and enhanced sea crude polysaccharides extracts usually contain protein and secondary
cucumbers survival and growth (Kang, Kwon, & Kim, 2003). Other metabolites, various purification procedures such as size-exclusion

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C. Xu et al. Journal of Functional Foods 49 (2018) 73–84

Table 2
Bioactive compounds of sea cucumber: extraction and purification.
Compound/raw material Extraction method Purification Ref.

Collagen/body wall Disaggregating process (water-EDTA-water-NaOH)→Pepsin N/A Adibzadeh et al. (2014), Liu
hydrolysis et al. (2017), Zhong et al.
(2015)
Polysaccharide/body wall Pepsin and trypsin hydrolysis → Ethanol precipitation Applied to macroporous adsorption Cui et al. (2016)
resin → anion-exchange chromatography
Fucoidan/body wall Lipids removed by acetone → Papain Sepharose Q Fast Flow column; size Hu, Xia, et al. (2014), Xu
hydrolysis → Cetylpyridinium chloride Exclusion chromatography et al. (2014)
precipitation → Fucoidanase
Lipids removed by acetone → Papain Anion-exchange chromatography Wang et al. (2016)
hydrolysis → Cetylpyridinium chloride and ethanol precipitation
Fucosylated chondroitin Papain hydrolysis → Cetylpyridinium chloride precipitation and Anion-exchange chromatography/HPLC Chen et al. (2011), Hu et al.
sulfate/body wall ethanol precipitation (2014)
Protease N Amano G hydrolysis → Ultrafiltration → Ethanol Anion-exchange chromatography; Shida et al. (2017)
precipitation→ ultrafiltration; gel chromatography
Cerebrosides/dried powder Extracted by CHCl3/ MeOH and EtOAc/n-BuOH Silica gel chromatography; RP-HPLC Xu et al. (2011)
Long-chain bases(sphingoid Cerebrosides extract → Extracted by n-hexane and ether Silica gel chromatography Liu et al. (2015)
bases)/dried powder Cerebrosides extract → Extracted by Ba(OH)2/Dioxane and Silica gel chromatography Tian et al. (2016)
diethyl ether
EPA-enriched phospholipids/ Extracted by CHCl3/ MeOH Silica gel chromatography Liu et al. (2014)
body wall
Saponins/body wall Refluxing with ethanol Ion Exchange Chromatography Hu et al. (2012)
Saponins Refluxing with ethanol Ion Exchange Chromatography; Silica gel Wang et al. (2014)
chromatography
Triterpene glycosides Refluxing with ethanol Silica gel chromatography; RP-HPLC Silchenko et al. (2017)
Peptides Enzymatic hydrolysis N/A Ghanbari et al. (2015), Li
et al. (2017)
Ethanol hydrolysis Silica gel chromatography Tan et al. (2013)
Protein extraction → Enzymatic hydrolysis Gel chromatography Zhou et al. (2012)
Oligopeptides/guts UV irradiation → Icubation → Extracted by trichloroacetic acid Sephadex G-15 gel chromatography Zheng et al. (2012)
Low-molecular-weight gelatin Gelatin preparation → Enzymatic hydrolysis Ultrafiltration Wang et al. (2010)
hydrolysate/body wall
Lectine/coelomic fluid Coelomic fluid → Ultra filtration membrane Phenyl sepharose column chromatography Gowda et al. (2008)

chromatography, high pH anion-exchange chromatography, gas–liquid Table 3

chromatography, high-performance liquid chromatography, and gel Current functional products based on sea cucumber on the market.a.
electrophoresis can be used to the prepare pure polysaccharides Brand Health functions Forms Price
(Venugopal, 2011). Fatty acids, peptides, triterpene glycosides are
usually purified by gel chromatography (Tian et al., 2016), ion ex- Swanson Joint health Capsule $0.10/count
change chromatography (Hu et al., 2012), and reverse phase high- Deep blue health Immune system support; joint Capsule $0.44/count
health
performance liquid chromatography (Silchenko et al., 2017). Ultra-
Hawaii pharm Antitumor Liquid $9.88/Fl Oz
filtration is commonly used to prepare specific peptides with desired Ultrahealth Immune system support Capsule $0.83/count
molecular range (Wang et al., 2010). NutriSea Joint health Capsule $0.22/count
Hernera N/A Liquid $6.00/Fl Oz
Freshell Nutritional support Tablet $0.22/count
MARINE CQ 500 Immune system support; joint Capsule $0.50/count
7. Sea cucumber based nutraceutical products health
Terravita N/A Powder $11.96/
Sea cucumber has been commonly sold in the form of dry raw ounce
products. Hong Kong, Guangzhou, China and New York, USA are the Holika Holika Anti-aging, Moisturizing, Anti- Essence $6.49/ounce
wrinkle, and firming
major markets for sea cucumber trading (Hair et al., 2012). Depending
Beauugreen Boosting skin elasticity and Facial mask $0.22/pcs
on species, body size, and processing integrity, the treading price metabolism
trading price can be widely changed, in Hong Kong and Guangzhou, Hwajin cosmetic Moisturizer and anti-wrinkle Cream $0.92/g
this price can be ranging from 15 to 385 US $/kg (Purcell, 2014). Al-
a
though sea cucumbers have been recognized for their various biological The information was obtained from www.amazon.com, the search key-
functions and beneficial effects, sea cucumber based nutraceutical words are “sea cucumber”, “sea cucumber extract”, and “sea cucumber pro-
duct”.
products have been under-developed and usually perceived as niche
products. Table 3 exemplifies the commonly found sea cucumber de-
Although various physically- and chemically-based methods have been
rived nutraceuticals in commercial market. It shows that the prices of
used to reduce the bitterness of various food products (Goldberg, Grant,
tablet/capsule based products range from US$ 0.10–0.83/count, and
Aliani, & Eskin, 2017), none of these methods have been used in the
the liquid products range from US$ 6.00–9.88/fl. oz.
development of sea cucumber nutraceuticals.
In the development and expansion of sea cucumber based nu-
Bioaccessibility and bioavailability are another two important fac-
traceuticals, several factors need to be considered such as organoleptic
tors in the development of sea cucumber based nutraceuticals.
property, bioaccessibility, bioavailability, and personally designed
Bioaccessibility is the amount of ingested nutrients that are available
products. Organoleptic property is an important factor in the develop-
for absorption in the gut after digestion, while bioavailability is the
ment of sea cucumber based nutraceuticals. The sensory properties of
fraction of ingested nutrients that is available for utilization in normal
the products need to meet consumers’ preference (Verbeke, 2006).
physiological functions or storage in the body (Sensoy, 2014). Bioactive
Bitter tasting is a common challenge in the development of sea cu-
compounds in sea cucumbers vary significantly in their bioaccessibility
cumber based products particularly when enzymatic hydrolysis is used.

80
C. Xu et al. Journal of Functional Foods 49 (2018) 73–84

and bioavailability. Proper processing technologies, such as micro-en- Borsig, L., Wang, L., Cavalcante, M. C. M., Cardilo-Reis, L., Ferreira, P. L., Mourão, P. A.
capsulation and gastro-resistant tablets, can be used to improve these S., ... Pavão, M. S. G. (2007). Selectin blocking activity of a fucosylated chondroitin
sulfate glycosaminoglycan from sea cucumber: Effect on tumor metastasis and neu-
two properties (Fonseca et al., 2017; Sensoy, 2014). trophil recruitment. Journal of Biological Chemistry, 282, 14984–14991.
Personalized nutrition is another important trend in the developing Cao, R.-A., Surayot, U., & You, S. (2017). Structural characterization of im-
sea cucumber based nutraceuticals. Personalized nutrition studies the munostimulating protein-sulfated fucan complex extracted from the body wall of a
sea cucumber, Stichopus japonicus. International Journal of Biological Macromolecules,
interaction between diet and genetic variants to optimize health or 99, 539–548.
prevent/treat diseases (Konstantinidou, Daimiel, & Ordovas, 2014). The Chang, Y., Hu, Y., Yu, L., McClements, D. J., Xu, X., Liu, G., & Xue, C. (2016). Primary
sea cucumber derived products need be to be diversified in their structure and chain conformation of fucoidan extracted from sea cucumber
Holothuria tubulosa. Carbohydrate Polymers, 136, 1091–1097.
functions to meet different requirements. For instance, specific sea cu- Chari, A., Mazumder, A., Lau, K., Catamero, D., Galitzeck, Z., & Jagannath, S. (2018). A
cumber products can be developed to antagonize obesity or antagonize phase II trial of TBL-12 sea cucumber extract in patients with untreated asympto-
high blood sugar content. matic myeloma. British Journal of Haematology, 180(2), 296–298.
Che, H., Du, L., Cong, P., Tao, S., Ding, N., Wu, F., ... Wang, Y. (2017). Cerebrosides from
sea cucumber protect against oxidative stress in SAMP8 mice and PC12 cells. Journal
8. Conclusion of Medical Food, 20(4), 392–402.
Chen, S., Hu, Y., Ye, X., Li, G., Yu, G., Xue, C., & Chai, W. (2012). Sequence determination
Sea cucumbers as a traditional tonic food contains a large number of and anticoagulant and antithrombotic activities of a novel sulfated fucan isolated
from the sea cucumber Isostichopus badionotus. Biochimica et Biophysica Acta (BBA) -
bioactive compounds including triterpene glycosides, fucoidan, fuco- General Subjects, 1820, 989–1000.
sylated chondroitin sulfate, sulfated fucan, and phenols. Various bio- Chen, S., Xue, C., Yin, L. A., Tang, Q., Yu, G., & Chai, W. (2011). Comparison of structures
logical activities of those compounds have been recognized such as anti- and anticoagulant activities of fucosylated chondroitin sulfates from different sea
cucumbers. Carbohydrate Polymers, 83, 688–696.
oxidation, anticancer, anti-inflammation, antithrombotic activities, Conand, C. (2006). Sea cucumber biology, taxonomy, distribution and conservation
anti-diabetes, anti-obesity, and anti-microbes. These biological func- status. Workshop on the conservation of sea cucumbers in the families Holothuriidae
tions provide an excellent opportunity to develop high-value sea cu- and Stichopodidae, pp. 33–50.
Cui, C., Wang, P., Cui, N., Song, S., Liang, H., & Ji, A. (2016). Sulfated polysaccharide
cumber based nutraceuticals. Organoleptic property and bioaccessi- isolated from the sea cucumber Stichopus japonicas promotes the SDF-1α/CXCR4
bility and bioavailability are major factors when developing sea axis-induced NSC migration via the PI3K/Akt/FOXO3a, ERK/MAPK, and NF-κB sig-
cucumber based nutraceuticals, while personalized nutrition is the fu- naling pathways. Neuroscience Letters, 616, 57–64.
Dakrory, A. I., Fahmy, S. R., Soliman, A. M., Mohamed, A. S., & Amer, S. A. (2015).
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