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
Sea cucumbers are cucumber-shaped marine invertebrates in the
class Holothuroidea. There are more than 1,100 varieties of sea cu-
cumbers in the world, among which about 40 species are available in
commercial markets (Conand, 2006). Sea cucumbers are popular tonic
foods in many Asian countries. Increasing demand has led to an over
exploitation and depletion of the natural stock of sea cucumbers
(Purcell et al., 2013). Improved aquaculture production and appro-
priate natural stock management practices are needed to maintain a
sustainable supply of sea cucumbers.
Sea cucumbers are commonly characterized by high protein and low
lipid contents (Wen, Hu, & Fan, 2010), with a diverse other compounds
such as peptides (Zhou, Wang, & Jiang, 2012), triterpene glycosides
(Silchenko et al., 2017), fucoidan (Hu et al., 2015), fucosylated chon-
droitin sulfate (Myron, Siddiquee, & Azad, 2014), cerebrosides (Xu
et al., 2011), sphingoid (Tian, et al., 2016) and phenols (Esmat, Said,
Soliman, El-Masry, & Badiea, 2013). As a result, sea cucumbers have
been reported to possess various biological functions such as anti-oxi-
dative activity (Wang et al., 2012), anticancer (Tian et al., 2005), anti-
inflammation (Song, Park, Cho, & Park, 2013), antithrombotic activity
(Matsuhiro, Osorio-Román, & Torres, 2012), anti-diabetes (Barky et al.,
2016), anti-obesity (Tian et al., 2016), and antimicrobial activity
(Pringgenies, 2013).
Many reviews have been published on specific biological functions
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.
et al. (2015) reported the functional characterization and mechanism of
the immune-related molecules. Triterpene glycosides have been widely
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 &
Franco, 2016). The biological and taxonomic perspectives (Honey-
Escandón, Arreguín-Espinosa, Solís-Marín, & Samyn, 2015) and struc-
ture and function relationships (Park, Bae, Kim, Stonik, & Kwak, 2014)
of these special group of compounds were also reported. Another im-
portant compound in sea cucumbers, polysaccharide fucosylated
chondroitin sulfate, was also reviewed (Myron, Siddiquee, & Al Azad,
2014; Pomin, 2014).
Although many reviews about sea cucumbers have been reported,
most reviews were focusing on specific groups of compounds and their
associated biological functions. From an application point of view, re-
ports on the use of sea cucumbers as functional foods and drug products
are still limited. There is also a lack of summary of the most recent
discoveries of sea cucumbers biological functions such as anti-diabetes,
anti-obesity and improvement of learning and memory (Bordbar,
Anwar, & Saari, 2011, Kiew & Don, 2012). Reviews of the extraction
and purification of active compounds from sea cucumbers have been
scarce. Additionally, reviews of the management practices to maintain a
sustainable sea cucumber supply have been largely neglected.
The aim of this review is to address the above shortcomings by
providing an update of the most recent discoveries of sea cucumber
biological functions and the associated bioactive compounds.
Considering the potential of developing sea cucumber-based nu-
traceuticals and pharmaceuticals, the practices of preparing pure
bioactive compounds and maintaining a sustainable sea cucumber
sources were discussed. The information will provide a comprehensive
perspective on developing sea cucumber based nutraceuticals.
2. Classification and identification of sea cucumbers
Sea cucumbers are soft-bodied marine animals that can be found on
the seabed all around the world (Conand, 2006). More than 1,100 sea
cucumber varieties have been reported among which the families Ho-
lothuridae, Stichopodidae, and Cucumariidae are most valuable for com-
mercial markets. Sea cucumbers originated from different locations
may differ in their food and medical values, it is therefore important to
specify their origins.
Sea cucumber species can be identified through their genetic char-
acteristics such as microsatellite (Kang et al., 2011; Kanno, Suyama, Li,
& Kijima, 2006; Kim, Choi, & An, 2008). Microsatellite analysis is based
on the fact that polymorphic DNA loci (microsatellite markers) contain
repeated nucleotide sequences and do not change among the same
species. Once the microsatellite-based markers are developed, the gene
differentiation between sea cucumber populations can be verified,
which can be further used to identify the species.
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
(Honey-Escandón et al., 2015). With the advancement of chemical
analytical methods, more and more special compounds in sea cu-
cumbers can be characterized to identify the geographical locations and
origins of sea cucumbers. For example, special pigments and proteins
located on sea cucumber body surface can be determined through
Desorption Atmospheric Pressure Chemical Ionization Mass Spectro-
metry (DAPCI-MS) (Wu, et al., 2009). The unique mid-infrared spec-
troscopy fingerprints of sea cucumbers can be analyzed through Diffuse
Reflectance mid-Infrared Fourier Transform Spectroscopy (DRIFTS)
(Wu, et al., 2010). Stable Isotope and Fatty Acid (SI-FA) analysis ac-
cesses sea cucumbers based on their δ13C and δ15N and fatty acid
profiles (Zhang, Liu, Li, & Zhao, 2017). Multi-elements analysis was
used to analyze sea cucumber elements profiles (Liu, Xue, et al., 2012).
With the appropriate data analyses such as principal components
74
Journal of Functional Foods 49 (2018) 73–84
analysis, cluster analysis, and discriminant analysis, these chemical
analytical methods proved high differentiating accuracy.
3. Active compounds in sea cucumbers
3.1. Overall chemical compositions of sea cucumbers
Sea cucumbers have long been regarded as a tonic food in Asian
countries. Proteins are the most abundant chemical components and
can account 40 ∼ 60 wt% of sea cucumber dry matter (Wen et al.,
2010). Most sea cucumber proteins are in the form of collagen with up
to 70 wt% of body wall proteins being insoluble collagen fiber (Saito,
Kunisaki, Urano, & Kimura, 2002). Glutamic acid (Bechtel, Oliveira,
Demir, & Smiley, 2013; Roggatz et al., 2017; Zhong, Khan, & Shahidi,
2007) and glycine (Saito et al., 2002; Wen et al., 2010) are two
dominant amino acids in sea cucumber proteins.
Fatty acids in sea cucumbers exist at a relatively small amount.
Total fatty acids account for 2 ∼ 8 wt% in sea cucumber dry matter,
among which unsaturated fatty acids can account for up to 70%.
Eicosapentaenoic acid (EPA, C20:5, n-3) in total fatty acids can be up to
56.7%, while the content docosahexaenoic acid (DHA, C22:6, n-3) was
much lower (up to 5.8% of total fatty acids) (Bechtel et al., 2013; Gao
et al., 2016; Salarzadeh et al., 2012; Zhong et al., 2007). Sea cucumbers
contain around 15 wt% carbohydrate in body wall and 8 wt% in muscle
bands (Bechtel et al., 2013). In addition to these three major compo-
nents, sea cucumbers are also rich in elements such as Ca, Mg, Fe, with
contents varying among different species (Barzkar, Fariman, & Taheri,
2017; Lee et al., 2014; Wen & Hu, 2010).
3.2. Collagens
Collagens as main structural proteins build sea cucumber body tis-
sues and contribute sea cucumbers’ palatable tastes (Liu, Zamora, Jeffs,
& Quek, 2017). Collagens in sea cucumbers commonly consist of three
polypeptide chains, each of which contains a repeating Glycine-X-Y
motif where X and Y represent any amino acids (Hulmes, 2008). As a
result, glycine is the most abundant amino acid in sea cucumber col-
lagen (Abedin et al., 2014; Adibzadeh, Aminzadeh, Jamili, Karkhane, &
Farrokhi, 2014; Lin et al., 2017; Liu et al., 2017; Zhong, Chen, Hu, &
Ren, 2015).
Collagen fibers are formed by covalent cross-links between col-
lagens. Electrophoretic assay revealed that sea cucumber fiber tissues
are thin, uniform and densely interwoven collagenous fibrils (Liu et al.,
2017). External factors such as temperature, salt concentration, sun-
light exposure, and nutrient deficiency can induce autolysis of sea cu-
cumber body walls, and drastically change of the tissues mechanical
properties such as contraction, relaxation and mucoid degeneration
(Liu et al., 2018).
3.3. Glycosides
Glycosides are molecules in which a sugar is bound to another
functional group via a glycosidic bond. Sea cucumbers contain tri-
terpene glycosides as abundant secondary metabolites. The unique
structure of triterpene glycosides contribute to their biological activity
and can be used as taxonomic markers (Honey-Escandón et al., 2015;
Kalinin, Avilov, Silchenko, & Stonik, 2015). The carbohydrate chains of
triterpene glycosides commonly contain xylose, glucose, quinovose, 3-
O-methylglucose, and in rare cases, 3-O-methylxylose, 3-O-methylglu-
curonic acid, 3-O-methylquinovose, and 6-O-acetyl-glucose (Kalinin
et al., 2015; Kalinin, Silchenko, Avilov, Stonik, & Smirnov, 2005).
Holostane type triterpene glycosides (lanostane derivatives with an
18(20)-lactone) is the most common triterpene glycosides found in sea
cucumbers.
C. Xu et al.
3.4. Polysaccharides
Sea cucumbers contain a various polysaccharides such as fucoidan,
fucosylated chondroitin sulfate, and fucan. The backbone of fucoidan is
built by (1–3)-linked tetrafucose repeated unit, with each fucose unit
having one or two HSO4 substitution on its cyclic structure (Chang
et al., 2016; Hu et al., 2015; Yu et al., 2014, 2013; Yu, Xue, et al.,
2014). Fucosylated chondroitin sulfate (FucCS) has chondroitin sulfate
type backbone with sulfated or non-sulfated fucose attached on side
chain (Myron et al., 2014). Some studies reported that fucan consists of
1 → 3 and/or 1 → 2 linked tetrasaccharide repeating units with sulfated
or non-sulfated fucose residues attached to its backbone chain (Cao,
Surayot, & You, 2017; Chen et al., 2012; Wu et al., 2015).
The complex structures of polysaccharides are responsible for their
biological functions. For example, Mulloy, Mourao, and Gray (2000)
reported that sulfated fucose branches in fucosylated chondroitin sul-
phate were crucial in exerting anticoagulant activity of sea cucumbers.
Trisaccharide units with 2,4-O-disulfated fucose branches in fucosy-
lated chondroitin sulphate played a critical role to facilitate neurite
outgrowth (Shida, Mikami, Tamura, & Kitagawa, 2017). Fucosylated
chondroitin sulphate and fucoidan with linear chains exhibited a more
potent of antihyperlipidemic activity than random chains (Li, Li, Zhi,
Wei, et al., 2017). In another study, Li, Li, Zhi, Hu, et al., (2017) re-
ported that different sulfation patterns in fucoidan accounted for sea
cucumbers anti-hyperlipidemic activities.
3.5. Phenols
Sea cucumbers are also good sources of phenols which play an
important role in antioxidant activity. The compositions of sea cu-
cumbers phenols are different from those derived in fruits and vege-
tables. Chlorogenic acid (up to 93 wt%) is the major phenolic compo-
nents in sea cucumbers while the content of ascorbic acid was very
minimal (Esmat et al., 2013; Fahmy 2015). Other phenols such as
pyrogallol, rutin, coumaric acid, and catechin were also detected in sea
cucumbers (Dakrory et al., 2015; Esmat et al., 2013; Fahmy, 2015). The
phenols contents in different tissues of the sea cucumbers also vary
widely (Mamelona et al., 2007).
4. Biological functions of sea cucumbers
Various biological functions in sea cucumbers have been reported.
Those functions are often species-specific and closely associated with
the bioactive compounds contained in sea cucumbers. A list of biolo-
gical functions and their bioactive compounds in related sea cucumber
species are summarized in Table 1 and explained below.
4.1. Anti-oxidative activities
Radical oxygen species (ROS) generated from various sources (mi-
tochondria, peroxisomes, NADPH oxidase, cytokines, UV radiation,
chemotherapeutic agents, and hyperthermia) can cause oxidative stress
and disturb human body physiological functions such as protein
structure modification, DNA damages, deviant cellular signaling, de-
creased proliferative response, and defective host defenses (Finkel &
Holbrook, 2000). Sea cucumbers exert strong capability of scavenging
ROS. For example, the fresh and rehydrated sea cucumber Stichopus
japonicus was reported to scavenge AAPH and DPPH radicals (Zhong
et al., 2007), while the organic/aqueous extract of Holothuria atra de-
monstrated Fe+ chelating activity and lipid peroxidation repressing
capability (Dakrory et al., 2015; Esmat et al., 2013).
Protein hydrolysates from sea cucumbers exhibit anti-oxidant ac-
tivities depending on molecular weight, amino acids composition and
peptide hydrophobicity (Zou, He, Li, Tang, & Xia, 2016). Peptides-rich
enzymatic hydrolysates from the sea cucumber Actinopyga lecanora
scavenged the DPPH radicals and showed a great Ferrous ion (Fe+)
75
Journal of Functional Foods 49 (2018) 73–84
chelating activity (Ghanbari et al., 2015). A low molecular weight of
antioxidant peptide contained 46.7% hydrophobic amino acids with a
sequence of GPEPTGPTGAPQWLR (Zhou et al., 2012). Zheng et al.
(2012) reported three sea cucumber antioxidant peptides, VTPT, VLLT,
and VGTVGM, contained 50%, 75%, and 50% hydrophobic amino
acids, respectively.
Polysaccharides in sea cucumbers also have anti-oxidative activities.
Polysaccharides prepared from Apostichopus japonicas demonstrated a
free radicals scavenging ability and reducing power; the poly-
saccharides had molecular weight of 36.2 kDa, with main composition
of glucosamine, galactosamine, glucuronic acid, mannose, glucose,
galactose and fucose (Liu et al., 2012). Sea cucumber fucoidan with a
molecular weight of 1614.1 kDa suppressed the expression of p-JNKs
and p-ERKs, two enzymes regulating the MAPKs pathway in response to
oxidative stress (Wang et al., 2012). Fucosylated chondroitin sulfate
derived from two sea cucumber species (A. molpadioidea and H. nobilis)
also exhibited a moderate antioxidant activity (Zou et al., 2016).
In addition to protein and polysaccharides, other compositions in
sea cucumbers such as polyphenols (Husni, Shin, You, & Chung, 2009;
Scalbert, Johnson, & Saltmarsh, 2005), flavonoids (Mamelona et al.,
2007), phospholipids and cerebrosides (Wu et al., 2014, 2013, 2012)
also exhibited anti-oxidative activities. Coelomic fluid collected from
sea cucumbers contains SOD, CAT and GR with high potent activities
(Dolmatova, Eliseikina, & Romashina, 2004).
4.2. Anti-cancer activities
A recent phase II clinical trial showed the effectiveness anti-cancer
of sea cucumber extract in vivo (Chari et al., 2018). In general, some
compounds in sea cucumbers can be potentially used as anticancer
products. For example, cerebrosides induce tumor cell apoptosis
through the mitochondria pathway (Du et al., 2012; Sugawara et al.,
2006). The extract of H. parva induced death of chronic lymphocytic
leukemia through mitochondria pathway without harming the healthy
B-lymphocytes (Salimi et al., 2017). Extracts from sea cucumbers also
demonstrated curative effects on skin-cancer (Kim et al., 2017).
A sulfated saponin extracted from the sea cucumber Pentacta
quadrangularis was observed an anti-angiogenesis effect through in-
hibiting the receptor of vascular endothelial growth factor (Tian et al.,
2005). The anti-cancer activity of sulfated saponin compounds was
further reported through suppressing the interaction between kinase
insert domain containing receptor and αvβ3 integrin (Tian et al., 2007).
Silchenko et al. (2017) reported that triterpene glycosides from the sea
cucumber Neothyonidium magnum exhibited not only a cytotoxic effect
on DLD-1 cells but also a synergism with anti-proliferative effect of
radioactive irradiation.
Metastasis is one hallmark of cancers with the possibility of curative
treatment for cancer patients being reduced significantly once metas-
tasis happens. Selectins interact with certain glycoproteins in cancer
cells and facilitate the development of cancer cells metastasis.
Fucosylated chondroitin sulfate extracted from the sea cucumber L.
grisea can effectively block the interaction between selectin and tumor
cells and inhibit the metastasis (Borsig et al., 2007). The mechanism
was due to the binding of fucosylated chondroitin sulfate to selectin
prior to tumor cells development (Borsig et al., 2007). Triterpene gly-
coside derived sea cucumbers also showed the anti-metastatic activity
(Zhao et al., 2011).
4.3. Anti-inflammation activities
Inflammation is a human reaction to harmful stimuli such as pa-
thogens and damaged cells. Appropriate inflammation reaction resists
the invasion of external pathogens and clears out or repairs the da-
maged cells. However, persisting and overreacted inflammation can
cause damage to human body and lead to cancers. Studies have shown
that sea cucumber extracts contain effective anti-inflammation
C. Xu et al. Journal of Functional Foods 49 (2018) 73–84

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

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

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

76
C. Xu et al.
2012). A fucan compound isolated from sea cucumbers has high anti-
thrombotic activity and was used to treat thrombosis with decreased
bleeding risk (Chen et al., 2012). A fucosylated chondroitin sulphate
compound exhibited a similar effect (Wu, Xu, Zhao, et al., 2010). The
anti-thrombotic activity of sea cucumber polysaccharides is closely re-
lated with their structures such as monomer composition, sulfate con-
tent, molecular size, and sulfated patterns (Li, Li, Yan, et al., 2017; Luo
et al., 2013). For example, fucosylated chondroitin sulphate demon-
strated an unusual pro-coagulant activity that is closely related with
charge density, sugar composition and molecular mass (Mansour et al.,
2017). However, when it goes through the gastrointestinal tract after
oral administration, biological functions of fucosylated chondroitin
sulphate can be negatively influenced by gastrointestinal tract before it
is absorbed by body. Gastro-resistant tablet formulation is a successful
solution to avoid this degradation (Fonseca, Sucupira, Oliveira, Santos,
& Mourão, 2017).
4.5. Anti-microbial activities
Sea cucumbers can be an important resource for anti-microbial
compounds, depending on the species, tissues, and solvents used for the
compounds extraction (Pringgenies, 2013). Two sea cucumber organs
isolated with ethyl acetate and methanol exhibited antimicrobial ac-
tivities (Mashjoor & Yousefzadi, 2017). In another study, the aqueous
methanol extract from sea cucumber body wall showed the best anti-
microbial activity (Shakouri, Shoushizadeh, & Nematpour, 2017). The
different sea cucumber anti-microbial activities were due to the dif-
ferent living environments and unique chemical substances such as
peptides (Schillaci et al., 2013), triterpene glycosides (Yuan, Yi, Xue,
Zhang, & La, 2008), and lectin (Gowda, Goswami, & Khan, 2008).
4.6. Anti-diabetic activities
Diabetes is caused by dysfunctional interaction between insulin
resistance and insulin secretion, resulting in hyperglycemia and leading
to damage of different organs in human body (Upadhyay et al., 2017).
Most recent studies have demonstrated the activities of treating and
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.
77
Journal of Functional Foods 49 (2018) 73–84
curing diabetes by sea cucumbers. The bioactive compounds in sea
cucumbers and their anti-diabetics mechanisms are summarized in
Fig. 1. As α-glucosidase plays an important role in diabetes, inhibition
of α-glucosidase can be an effective method to treat diabetes (Upadhyay
et al., 2017). A study found that sea cucumbers fatty acids exerted anti-
hyperglycemic activity by inhibiting α-glucosidase activity (Nguyen &
Kim, 2015). Fucoidan isolated from the productive sea cucumber A.
molpadioides was capable of down-regulating serum resistin, leptin and
TNF-α and increasing hepatic glycogen (Hu, Xia, et al., 2014). Fuco-
sylated chondroitin sulfate can improve insulin sensitivity and glucose
metabolism through regulating the key genes for phosphorylation, such
as p85-PI3K, Ser473-PKB, and Thr308-PKB in PI3K/PKB pathways (Hu,
Chang, et al., 2014; Hu et al., 2014). The anti-diabetic activity of EPA-
rich phosphatidylcholine derived from sea cucumbers was reported
through decreasing blood glucose level, augmenting serum insulin and
glycogen contents by regulating PI3K/PKB pathways (Hu, Xu, et al.,
2014). Numerous studies indicate saponins in sea cucumbers can po-
tentially treat diabetes through increasing serum insulin and glycogen
levels (Barky et al., 2016). In addition to saponins, some polypeptides
in sea cucumbers also exhibited anti-hyperglycemic activity (Li, Xu, &
Su, 2017).
4.7. Anti-obesity activities
In general, bioactive compounds treat obesity commonly through
the following mechanisms: (1) appetite control, (2) blocking fat ab-
sorption, (3) stimulating energy, (4) suppressing adipose tissue growth,
and (5) increasing body fat mobilization (Hu, Tao, et al., 2016). The
anti-obesity activities have been reported for various sea cucumbers
compounds through alleviating metabolic syndrome (Fig. 2). A fu-
coidan compound isolated from the sea cucumber Acaudina molpa-
dioides significantly decrease fat content in vitro (Xu et al., 2014). Fu-
cosylated chondroitin sulfate obtained from the sea cucumber Acaudina
molpadioides can inhibit adipose (fat) tissue growth (Xu, Wang, et al.,
2015a, 2015b). The anti-obesity mechanisms of fucoidan and fucosy-
lated chondroitin sulfate are similar, i.e., activating the Wnt/β-catenin
pathway which negatively influences on adipocyte differentiation;
C. Xu et al.
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
oppresses two key enzymes fatty acid synthase (FAS) and glycerol-3-
phosphate acyltransferase (GPAT) in fat tissue growth. Phospholipid
(Liu et al., 2014, 2015; Tian et al., 2016; Vaidya & Cheema, 2014) and
cerebroside (Liu et al., 2015) in sea cucumbers have also exhibited anti-
obesity activities. At cellular level, Wnt/β catenin pathway also plays
an important role in anti-obesity effect of cerebrosides. For example,
cerebrosides from the sea cucumber Cucumaria frondosa suppressed
adipogenic transcription factors involved in Wnt/β-catenin pathway
(Xu, Wang, et al., 2015a, 2015b). Vanadium purified from the sea cu-
cumber Apostichopus japonicas inhibited adipocytes differentiation
through activating Wnt/β-catenin pathway (Liu, Xu, Xue, et al., 2015).
4.8. Improving learning and memory
Recent studies also reported the improvement of learning and
memory capabilities of sea cucumbers. Fig. 3 shows the mechanisms of
improving learning and memory for sea cucumber derived bioactive
compounds. Fatty acids in sea cucumber can effectively improve im-
paired learning and memory functions related to aging and neuro-de-
generative diseases (Che, et al., 2017; Wu et al., 2014; Zhou et al.,
2016). Phosphatidylcholine from sea cucumber can inhibit the activity
of AchE, which attacks AcH, an important neurotransmitter in learning
and memory (Zhou et al., 2016). Cerebrosides, a group of complex li-
pids, improved the cognitive performances of mice by decreasing the
content of MDA, 8-OHdG, 8-oxo-G, and NO, and facilitating the activity
of SOD; cellular study found that cerebrosides inhibited the cell apop-
tosis by regulating the expression of apoptosis-related proteins, such as
Bax, Caspase-9, cleaved Caspase-3, and Bcl-2 (Che et al., 2017). Phos-
pholipids in sea cucumbers also showed similar effects by exerting
antioxidant effects and inhibiting cell apoptosis (Wu et al., 2014).
4.9. Other bioactivities
Sea cucumbers also exhibit a variety of other biological activities.
For example, phenolic compounds extracted from in sea cucumbers can
normalize biological indexes (serum direct bilirubin, alanine, aspartate
aminotransferases, hepatic malondialdehyde, hydroxyproline con-
centrations and antioxidant enzyme activities). Histologic results
78
Journal of Functional Foods 49 (2018) 73–84
showed sea cucumber extract significantly alleviated degeneration of
liver cell and regression of liver fibrosis and necrosis (Esmat et al.,
2013). A recent study showed that sea cucumber peptides with small
molecular weight alleviated the fatigue (Ye, Shen, Huang, Zhang, &
Xiao, 2017). Polysaccharides such as glycosaminoglycans and fucan are
potent anti-hyperlipidemic compounds (Li et al., 2017; Liu, Fau, Hu, &
M.-L., & Hu, M. L. , 2002; Liu et al., 2012). Diets containing the sea
cucumber Isostichopus badionotus inhibited high cholesterol through the
induction of key genes related to cholesterol and lipid metabolism
(Olivera-Castillo et al., 2013). Sea cucumber peptides can also inhibit
angiotensin-I converting enzyme for treating hypertension (Ghanbari,
et al., 2015; Sadegh Vishkaei et al., 2016).
5. Sea cucumber sources
5.1. Natural stock fishery
Traditionally, sea cucumbers have been mainly obtained through
natural catching and fishery. Worldwide, sea cucumbers are produced
and exported from several regions such as Asian Pacific (Indonesia, the
Philippines, Singapore, Malaysia, Papua New Guinea, Solomon Islands,
Fiji and Australia), Middle East (United Arab Emirates, Yemen) and
some African countries (Mozambique, Kenya, Madagascar and South
Africa) (Ferdouse, 2004). However, the over-exploitation and depletion
of natural sea cucumber stocks has been a serious concern, particularly
in Asian Pacific region (Purcell et al., 2013). In order to maintain a
healthy and sustainable sea cucumber source, appropriate management
practices such as limited harvesting, setting up catching quotas, and
rotational harvesting (Purcell, Lovatelli, & Pakoa, 2014; Purcell et al.,
2013) need to be implemented.
Limited harvesting is usually achieved by shortening fishing seasons
and/or setting specific number or species allowed to be harvested
(Purcell, Polidoro, Hamel, Gamboa, & Mercier, 2014). In order to plan
an appropriate fishing season, sea cucumber stock in a specific area
must be carefully monitored. Wolff, Schuhbauer, and Castrejón (2012)
reported a method to estimate sea cucumber stocks based on macro-
zone differences in density and distribution. Prescott et al. (2013) re-
ported a method to estimate sea cucumber abundance and exploitation
rates by continually removing animals in specific area. A passive
C. Xu et al.
integrated transponder tagged onto sea cucumber was used to monitor
specific species (Gianasi, Verkaik, Hamel, & Mercier, 2015). Rotational
harvesting is another practice commonly used to improve biological
and economic performance of aquatic animals (Plagányi, Skewes,
Murphy, Pascual, & Fischer, 2015). However, a recent study revealed
that sea cucumbers, unlike agricultural crops with more predictable
growth, are less robust to grow in a natural environment (Purcell,
Uthicke, Byrne, & Eriksson, 2015). Therefore, the practice of rotational
harvesting needs to be used cautiously when it is applied to sea cu-
cumbers.
5.2. Aquaculture
Aquaculture is another approach to produce sea cucumbers but with
some challenges. Diseases such as rotting edges, ulceration of the sto-
mach, autolysis of young juveniles, skin ulceration, erosion of epidermis
and body oedema can account for up to 80% mortality of cultured sea
cucumbers (Liu et al., 2010; Wang et al., 2007; Wang, Zhang, Rong,
Chen, & Shi, 2005). Environmental factors such as water temperature
and salinity also significantly influence phagocytosis and enzyme ac-
tivity of sea cucumbers (Wang, Yang, Gao, & Liu, 2008). The optimal
temperature for food intake by sea cucumbers was reported to be
14 ∼ 15 °C (Yang, et al., 2005). In another study, the optimal tem-
perature for larval growth of the sea cucumber Holothuria spinifera was
28 ∼ 32 °C (Asha & Muthiah, 2005). Temperature fluctuation could
promote sea cucumber larval growth but with a little impact on lipid
content and oxygen consumption (Dong, Dong, Tian, Wang, & Zhang,
2006). Sea cucumber culture also requires balanced nutrients. Protein
content, amino acids constitution, and calcium to phosphorus ratio are
important factors to promote sea cucumber growth (Sun et al., 2004). In
addition to the basic nutrients needs, other nutritional sources such as
dietary sea mud and yellow soil (Liu, Dong, Tian, Wang, & Gao, 2009),
small periphitic diatoms (Ito & Kitamura, 1997), algae (Yuan et al.,
2006) and bivalve wastes (Slater, Jeffs, & Carton, 2009; Yuan et al.,
2006) were also used in sea cucumber culture based on the unique
characteristics of these ingesting deposit matters.
Co-culturing sea cucumber with other aquatic animals was also at-
tempted in order to improve sea cucumbers survival and growth. A co-
culture system containing sea cucumbers and juvenile charm abalones
significantly reduced the water nitrogen content and enhanced sea
cucumbers survival and growth (Kang, Kwon, & Kim, 2003). Other
79
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.
aquatic animals used in co-culturing with sea cucumbers can be fish,
shrimp and green-lipped mussel. Sea cucumber co-cultured under fish
cage can avoid predators, adverse environmental conditions, and obtain
food supply from fish cage (Yokoyama, 2013). When co-cultured with
shrimp or mussel, sediments and fecal produced by those animals
provided nutrients to sea cucumbers (Slater & Carton, 2007; Zhou et al.,
2017).
6. Extraction and purification of bioactive compounds in sea
cucumbers
Extraction of bioactive compounds from sea cucumbers often fol-
lows the procedures of pretreatment, extraction and purification. In the
pretreatment step, sea cucumbers are dried and pulverized into powder.
The most common drying methods used are sun drying and freeze-
drying. Other drying methods such as microwave drying (Duan, Zhang,
Mujumdar, & Wang, 2010), ultrasound drying (Duan, Zhang, Li, &
Mujumdar, 2008), electro-hydrodynamic drying (Bai, Qu, Luan, Li, &
Yang, 2013; Bai, Yang, & Huang, 2012), and infrared radiation drying
(Moon, Kim, Chung, Pan, & Yoon, 2014) were also reported to improve
sensory characteristics and reduce nutrition loss.
After drying, the active compounds in sea cucumbers can be ex-
tracted. Table 2 summarizes the various methods used for extraction.
Organic solvent based extraction is commonly used. For example, tri-
terpene glycosides was extracted with refluxing 60% ethanol at
70–85 °C (Guo et al., 2015; Hu et al., 2012). Cerebrosides was extracted
with CHCl3/MeOH and EtOAc/n-BuOH mixture followed with acetone
washing (Xu et al., 2011). As an alternative to organic-solvents, enzy-
matic extraction can also be used to extract sea cucumber active com-
pounds. Under appropriate pH, temperature, reaction time, and enzyme
to substrate ratio, enzymes can target specific sites of proteins to pro-
duce desirable bioactive peptides (Ghanbari et al., 2015) and extract
polysaccharides (Yu et al., 2013). Recently, supercritical fluid extrac-
tion as an environment-friendly technique has been increasingly used in
extracting sea cucumbers bioactive compounds (Grosso, Valentão,
Ferreres, & Andrade, 2015). This method is particularly appealing to
produce high-value nutraceuticals from sea cucumbers.
A purification step is usually following the extraction step to pro-
duce pure compounds from sea cucumbers (Table 2). For example,
crude polysaccharides extracts usually contain protein and secondary
metabolites, various purification procedures such as size-exclusion
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
Polysaccharide/body wall
Fucoidan/body wall
Fucosylated chondroitin
sulfate/body wall
Cerebrosides/dried powder
Long-chain bases(sphingoid
bases)/dried powder
EPA-enriched phospholipids/
body wall
Saponins/body wall
Saponins
Triterpene glycosides
Peptides
Oligopeptides/guts
Low-molecular-weight gelatin
hydrolysate/body wall
Lectine/coelomic fluid
Disaggregating process (water-EDTA-water-NaOH)→Pepsin N/A Adibzadeh et al. (2014), Liu
hydrolysis et al. (2017), Zhong et al.
(2015)
Pepsin and trypsin hydrolysis → Ethanol precipitation Applied to macroporous adsorption Cui et al. (2016)
resin → anion-exchange chromatography
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
Papain hydrolysis → Cetylpyridinium chloride precipitation and Anion-exchange chromatography/HPLC Chen et al. (2011), Hu et al.
ethanol precipitation (2014)
Protease N Amano G hydrolysis → Ultrafiltration → Ethanol Anion-exchange chromatography; Shida et al. (2017)
precipitation→ ultrafiltration; gel chromatography
Extracted by CHCl3/ MeOH and EtOAc/n-BuOH Silica gel chromatography; RP-HPLC Xu et al. (2011)
Cerebrosides extract → Extracted by n-hexane and ether Silica gel chromatography Liu et al. (2015)
Cerebrosides extract → Extracted by Ba(OH)2/Dioxane and Silica gel chromatography Tian et al. (2016)
diethyl ether
Extracted by CHCl3/ MeOH Silica gel chromatography Liu et al. (2014)
Refluxing with ethanol Ion Exchange Chromatography Hu et al. (2012)
Refluxing with ethanol Ion Exchange Chromatography; Silica gel Wang et al. (2014)
chromatography
Refluxing with ethanol Silica gel chromatography; RP-HPLC Silchenko et al. (2017)
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)
UV irradiation → Icubation → Extracted by trichloroacetic acid Sephadex G-15 gel chromatography Zheng et al. (2012)
Gelatin preparation → Enzymatic hydrolysis Ultrafiltration Wang et al. (2010)
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.
and bioavailability. Proper processing technologies, such as micro-en-
capsulation and gastro-resistant tablets, can be used to improve these
two properties (Fonseca et al., 2017; Sensoy, 2014).
Personalized nutrition is another important trend in the developing
sea cucumber based nutraceuticals. Personalized nutrition studies the
interaction between diet and genetic variants to optimize health or
prevent/treat diseases (Konstantinidou, Daimiel, & Ordovas, 2014). The
sea cucumber derived products need be to be diversified in their
functions to meet different requirements. For instance, specific sea cu-
cumber products can be developed to antagonize obesity or antagonize
high blood sugar content.
8. Conclusion
Sea cucumbers as a traditional tonic food contains a large number of
bioactive compounds including triterpene glycosides, fucoidan, fuco-
sylated chondroitin sulfate, sulfated fucan, and phenols. Various bio-
logical activities of those compounds have been recognized such as anti-
oxidation, anticancer, anti-inflammation, antithrombotic activities,
anti-diabetes, anti-obesity, and anti-microbes. These biological func-
tions provide an excellent opportunity to develop high-value sea cu-
cumber based nutraceuticals. Organoleptic property and bioaccessi-
bility and bioavailability are major factors when developing sea
cucumber based nutraceuticals, while personalized nutrition is the fu-
ture trends to develop future sea cucumber based products.
Acknowledgements
This project was funded by Start-up Foundation of Returned
Oversea Student [grant numbers CYZZ20160411163623164] from
Shenzhen Scientific and Technological Innovation Commission.
Declarations of interest
None.
Ethics statement
The authors agree upon standards of expected ethical behavior.
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