Introduction
Sea cucumbers, marine invertebrates belonging to the phylum Echinodermata and specifically
to the class Holothuroidea, are fishery products that possess a high economic value
and potent medicinal properties (1, 2). In terms of physical appearance, sea cucumbers
are tube-like marine animals with skin that resembles a leathery material (2). As
of late, research has been conducted on sea cucumbers, especially on their role as
a functional food. Sea cucumbers, especially Actinopyga mauritiana, contain a high
percentage of protein or peptides (63.3 ± 0.43%), with glycine as its most abundant
amino acid. A. mauritiana also possesses a low lysine:arginine ratio. Both properties
are shown to exert hypocholesterolemic effects (3). Sea cucumbers also contain certain
proteins (bioactive peptides), polysaccharides, and saponins, and when extracted,
these compounds are shown to exert anticancer effects (4, 5). Saponins from sea cucumbers
promote osteoblast differentiation or osteogenic differentiation from pre-osteoblasts
by activating molecular pathways of BMP2/Smads activation in MC3T3-E1 cells (6). More
interestingly, sulfated polysaccharides in sea cucumber have the potential to be used
as health-improving agents and processed through technology and combining (7), such
as into functional food. Sea cucumber is a potential functional food based on the
medicinal properties mentioned above. Hence, this article's main aim is to interpret
the latest findings on potential applications of sea cucumbers as a functional food.
Sea cucumbers in general
Sea cucumbers, also known as teripang, “trepan,” or“beche-de-mer,” are marine invertebrates
that belong to the phylum Echinodermata and the class Holothuroidea. Sea cucumbers
can be found in deep seas and have a long history of being used as food and medicine
in the Middle East and Asia (1). It possesses a tube-like soft body with leathery
skin. The shape of sea cucumbers resembles that of a cucumber, hence the name (1,
3). Currently, there are about 1,716 species of sea cucumbers in the world, and the
most biodiverse of sea cucumbers are located in the Asia Pacific region (3). Some
commonly consumed sea cucumbers that possess health benefits are Holothuria leucospilota,
Bohadschia argus, Pearsonothuria graeffei, Holothuria polii, Colochirusancep, Holothuria
arenicola, Cucumaria japonica, and several others (4). Sea cucumbers contain numerous
bioactive compounds such as chondroitin sulfates, saponins, peptides, and glycosaminoglycan,
and these compounds possess anticoagulation, antiangiogenesis, anticancer, antidiabetic,
and antibacterial activities (5). Besides, sea cucumbers also contain micronutrients
such as thiamine or vitamin B1, B2 or riboflavin, B3 (niacin), vitamin A (retinol,
retinyl esters), calcium, iron, zinc, and magnesium (4).
Anticancer property of sea cucumbers
As mentioned previously, sea cucumbers exhibits an anticancer activity. Anticancer
activities can be achieved through cytotoxic activity, apoptosis induction, cell cycle
arrest, tumor growth reduction, metastasis inhibition, and drug resistance inhibition
methods (Figure 1) (4). Cytotoxic activity is achieved by blockage or growth prevention
of cancer cells. Holothuria scabra species produce bioactive carbohydrate compounds
such as holothurine A3 and A4 that were shown to be cytotoxic in hepatocellular carcinoma
(Hep-G2) and epidermoid carcinoma (KB) cell lines (8). In the apoptosis induction
aspect, Frondanol A5, a compound obtained from Cucumaria frondosa extract, caused
apoptosis in S2013 and AsPC pancreatic cancer cells (9). Cell cycle arrest is also
a potential mechanism for inhibiting cancer cell growth. Pearsonothuria graeffei contains
Ds-echinoside A and Echonoside A that disrupt the G0/G1 cell cycle process of liver
carcinoma cells (Hep-G2), disrupting the preparation for DNA replication (10). Pentacta
quadrangulari possesses a tumor growth reduction ability because of its saponin content,
specifically Philinopsides E and A in sarcoma 180 and hepatoma 22 mouse models (11,
12). P. graeffei contains Ds-echinoside A, which prevents cell migration and invasion,
and adhesion of hepatocellular carcinoma (Hep-G2) cells, hence reducing the probability
of metastasis (development of new cancer site) of cancer cells (13). Cancer cells
could develop drug resistance; hence drug resistance inhibition is crucial in chemotherapy
(4). Cucumariaokhotensis possesses a type of saponin named Frondoside A that inhibits
autophagy to survive in human urothelial carcinoma cell lines. Hence, cancer drug
resistance is inhibited (14).
Figure 1
Sea cucumbers effect possible-scheme for anti-cancer and anti-cholesterol.
Anticholesterol property of sea cucumbers
Diverse sea cucumbers have demonstrated that they could be an intriguing natural source
of useful substances because they contain amino acids, vitamins, triterpene glycosides,
PUFAs, flavonoids, polysaccharides, carotenoids, minerals, collagen, gelatin, phenolic,
saponin, and bioactive peptides (3, 15). From a nutritional standpoint, sea cucumber
is the perfect food with medical significance, since it includes more proteins and
less fats than most other foods. Bioactive compounds and pigments in sea cucumbers
exhibit an antioxidant activity, which may have the potential to improve cholesterol
and reduce the possibility of atherosclerosis using many capable mechanisms (Figure
1) (16). Polysaccharides from Apostichopus japonicus also have antihyperlipidemic
and antioxidant attributes (17). Triterpene glycosides (or triterpene saponin) exhibit
hypolipidemic (18), anti-inflammatory (19), immunomodulatory (20), and wound-healing
properties (21), which indirectly contribute to dyslipidemia. Triterpene glycosides
are also known to interact with sterol in the membrane of sea cucumbers as a self-defense
mechanism against saponin (22, 23). In obese mouse models, sterol sulfate significantly
reduced insulin resistance with inflammation induced by high-fat, high-fructose diets
(24). The saponin from sea cucumbers has been proved to suppress adipose accumulation
(Figure 1) (25), lower lipid levels, and attenuate atherosclerosis (26). Saponin can
also modulate cholesterol metabolism in Thelenota ananas (27). These facts stated
the health-related beneficial effects of the both saponin and the sterol in sea cucumbers.
The lipid content of Australostichopus mollis consists of high levels of 54% PUFA
compared to MUFA (23%) and SFA (24%), with arachidonic acid followed by eicosapentaenoic
acid as the dominant PUFA (28). Replacing SFAs with PUFAs was known to reduce total
cholesterol levels and provide beneficial cardio-metabolic effects (29–31). Wen et
al. (32) also found that arachidonic acid was the dominant composition of PUFAs in
many species of sea cucumbers. They further elaborated that while fatty acid profiles
varied between species, amino acid levels were comparable. These facts suggest the
potential of sea cucumbers as a high-protein source with low total fat and high unsaturated
fatty acid contents. The sea cucumber powder (33) and dietary glucosylceramide from
sea cucumber (34) also significantly decreased the cholesterol level in mice models
fed with high fat-enriched diet.
Future functional food product development of sea cucumbers
Significant efforts have been made to identify more therapeutic-related food and their
pharmaceutical applications, along with the growing understanding of the health-beneficial
properties of compounds derived from sea cucumbers. The numerous therapeutic benefits
of sea cucumbers and their valuable bioactive components have shown their potential
as both functional meals and a natural source of novel multifunctional medications
(35). However, despite high hopes, only a few foodstuffs made from sea cucumbers are
available in the food and medical industries now. One of the techniques to utilize
sea cucumbers as a functional food product would be to fortify food and health products
with sea cucumbers to increase the customer acceptability of sea cucumbers effectively.
Moreover, depending on seasonal fluctuations, geographic location, and feeding practices,
sea cucumbers' proximate composition varies significantly, resulting in sea cucumbers
being versatile food ingredients to be utilized for a specific health benefit or personalized
nutrition (15). Xu et al. (36) also emphasized that the potential for creating high-quality
nutraceutical products by extraction and purification of bioactive chemicals found
in sea cucumbers has not been completely explored.
Discussions
The morbidity due to cancer has increased daily in both developed and developing nations,
and it is one of the major causes of death, as nearly ten million deaths are caused
by cancer every year worldwide (37). Another illness condition is high body cholesterol,
which also affects people universally and may be a primary cause of several disorders
such as atherosclerosis, and cardiovascular diseases. Therefore, there is an urgent
need for a remedy that can be used to treat these ailments. Marine organisms are augmented
for development of drugs; about 10% of these creatures' extracts contain anticancer
attributes. In addition, the organisms' extracts are categorized by reduced drug resistance,
lower toxicity, safety, and high efficiency (5). Sea cucumber has been explored for
its anticancer and cholesterol-lowering activities due to the presence of potential
bioactive components (Figure 1). For instance, sea cucumber (golden) contains several
bioactive components such as saponin, flavonoids, docosahexaenoic and eicosapentaenoic
acid (EPA-DHA), proteoglycans, mucopolysaccharide, heparin sulfate, heparin, dermatan
sulfate, chondroitin sulfate, hyaluronic acid, glycosaminoglycan, collagen, and glycoprotein
and has several promising attributes beyond its nutritional qualities (38–40). In
conclusion, the opinion suggested that sea cucumber and its derived bioactive peptide
and carbohydrate components could be a point of great interest for future research
as a potential treatment for cancer and cholesterol illnesses (Figure 1). It is just
an opinion that summarizes sea cucumber's potential as a new hope for these ailments,
but for validation of these health benefits, there is a need to perform extensive
studies (especially in vivo and clinical trials); after that, it may be further considered
for development of functional foods or nutraceuticals.
Author contributions
NS, FN, MH, and WG contributed to the conception and design of the opinion-study and
drafted the manuscript first. MS, FN, and RM edited, revised, and approved the final
version of the submitted manuscript. All authors contributed to the article and approved
the submitted version.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial
or financial relationships that could be construed as a potential conflict of interest.
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