The proximate composition of sea cucumbers varies with species, feeding regimes, geographical location (Oh et al. 2017), and seasonal variation (Aydin et al. 2011) (Table 1). While sea cucumbers are known to have a high protein content, they are primarily consumed because of their flavor rather than nutritional value. Informing consumers on the nutritional composition of sea cucumbers may help them to appreciate the benefits of including this seafood in their diet (Barzkal et al. 2017).

The proximate moisture, ash, protein, and fat composition of fresh sea cucumbers varies from 67.93–93.01%, 2.01–7.86%, 3.40–8.86%, and 0.09–2.43%, respectively. Most fresh sea cucumbers have higher moisture content in their body wall than other seafood (Salarzadeh et al. 2012). Their high moisture content was considered as a tonic by fisheries when going to sea. Ash content varies with the mineral deposits and other inorganic matter in sea cucumber (Al Azad et al. 2017). The species, food, feeding patterns, environmental conditions, and reproductive activity may influence sea cucumber fat content (Lee et al. 2012).

The drying process alters the moisture, ash, protein, and fat content of fresh sea cucumber to 4.03–16.19%, 5.75–48.22%, 36.99–72.25%, and 0.55–8.19%, respectively. Fully dried sea cucumber material may contain high protein and is sold as a nutraceutical in capsule and tablet forms (Bordbar et al. 2011).

Minerals, such as calcium, sodium, magnesium, and phosphorus, are essential to humans. Unfortunately, information about mineral content in sea cucumbers is limited (Gocer et al. 2018). However, measurements of calcium (656–5700 mg/100 g dry weight (DW)), potassium (30–360 mg/100 g DW), and magnesium (155–4750 mg/100 g DW) suggest that sea cucumbers could be a viable alternative natural source of minerals (Table 2). Major mineral content appears to vary by sea cucumber species. Season, maturity, age, water temperature, availability of food, type of diet, and feeding system are reported to influence macro mineral levels in seafood (Oglunoglu and Oglunoglu 2017). For example, the phosphorus content is considerably high in Holothuria scabra (86.69 mg/100 g wet weight (WW)) (Table 2). In addition, sea cucumbers are reported to contain vitamins, including A, B1, B2, and B3 (Bordbar et al. 2011).

The amino acid profiles of various sea cucumber species have been reported and are found to be influenced by species and geographic location (Table 3). As free amino acids can affect the quality of marine foods (Sicuro et al. 2012), it is important to measure their content as well. In their free form, amino acids give rise to sweetness, bitterness, sourness, and umami; in particular, glutamic acid imparts a distinctive flavor and taste. Glycine (7.41–19.17 mg/100 g DW) was the major free amino acid in almost all species, and glutamic acid (4.97–13.10 mg/100 g DW), aspartic acid (4.48–15.71 mg/100 g DW), and alanine (3.7–11.72 mg/100 g DW) were also prominently featured (Table 3). Notably, cysteine is the only amino acid not ubiquitously found in sea cucumbers but is one of the most prevalent free amino acids in Parastichopus californicus (Table 3).

Fatty acid composition varied with species and habitat, with many species having a different dominant fatty acid (Table 4). However, arachidonic acid and cis-5,8,11,14,17-eicosapentaenoic acid were prominent components in most of the species. Surprisingly, palmitoleic acid was the major component in P. californicus but was absent in Stichopus japonicus and Actinopyga mauritiana. cis-10-Pentadecenoic acid, the major component in both A. mauritiana and H. arenicola, was not detected in Apostichopus japonicus, Athyonidium chilensis, H. mammata, H. tubulosa, H. poli, or P. californicus. Stearic acid has been detected in all species but is the major component only in A. chilensis.

Cancer remains a leading cause of death worldwide. Although high cure rates are achievable with currently available drugs, these produce a wide range of side effects (Sajwani 2019). As such, the identification of alternative, and potentially less toxic, anticancer agents derived from natural products is being pursued. Owing to their natural origin and inclusion in nutritional food products, bioactive compounds isolated from sea cucumbers are being investigated for use as anticancer agents. However, the mechanism of these compounds’ anticancer activities is unclear and requires a comprehensive study (Eso et al. 2020).

Similar, noncytotoxic concentrations of an ethanolic extract and aqueous fraction of H. poli were reported to decrease the proliferation of MDA-MB-231 human breast cancer cells by more than 50% and arrest the treated cells in S-phase (Kareh et al. 2018). In this study, petroleum ether, chloroform, ethyl acetate, and n-butanol organic fractions showed no significant activity.

A chloroform extract of H. nobilis collected from Philippine sea waters was reported to contain an antitumor agent more potent and toxic (acute) than Taxol and etoposide. Hexane and chloroform extracts of H. fuscopunctata and a chloroform extract of S. chloronotus also exhibit weak antitumor activities in brine shrimp and are more toxic than standard anticancer drugs (Layson et al. 2014). Three triterpene glycosides, fuscocineroside C (1), scabraside D (2), and 24-dehydroechinoside A (3), were isolated from H. scabra and showed significant cytotoxicity compared to 10-hydroxycamptothecin against five human tumor cell lines, P-388, MKN-28, A549, HCT116, and MCF-7 (Han et al. 2012) (Fig. 1).

The activity of scabraside D, a sulfated triterpene glycoside extracted from H. scabra, against human cholangiocarcinoma (HC) was investigated both in vitro and in vivo for tumor growth inhibition using a xenograft mouse model (Assawasuparek et al. 2016). Scabraside D (12.5–100 µg/mL) significantly decreased the viability and migration of HC cells in a dose-dependent manner with an IC₅₀ of 12.8 ± 0.05 µg/mL at 24 hours. Scabraside D (1 mg/kg/d for 21 days) also significantly reduced the growth of HC xenografts in mice without any adverse effects. Therefore, scabraside D may be a new therapeutic agent for cholangiocarcinoma treatment.

Various solvent extracts of the red sea cucumber, A. japonicus, were evaluated in colon cancer (HT-29), undifferentiated myeloid (HL-60), and hepatocarcinoma (Hep-G2) cells (Park et al. 2011). All fractions showed little cytotoxic activity against Hep-G2 cells, while the chloroform and ethyl acetate fractions showed more than 80% and 60% growth inhibition, respectively, in HL-60 and HT-29 cell lines. A comparison of canthaxanthin extraction methods from A. japonicus showed that ultrasonication extracted more canthaxanthin than either ethanol or water extraction and displayed higher inhibition (93.5%) against human malignant cell growth (Kim et al. 2017). The ultrasonication extract was found to inhibit both cancer cell proliferation and metastasis by downregulating skin tumor-promoting genes, such as B-cell lymphoma 2 (Bcl-2), matrix metalloproteinase-9 (MMP-9), and signal transducer and activator of transcription 3 (STAT3).

The antitumor activity of saponins and polysaccharides extracted from A. japonicas and Acaudina leucoprocta was investigated by testing the density gradient of S180 cells with various concentrations of saponin (S1 and S2) and polysaccharide (P1 and P2) extracts (Su et al. 2011). S1, P1, and P2 were extracted from A. leucoprocta, while S2 was extracted from a concentrated liquid of A. japonicus. The cytotoxic activities of S1 and S2 in S180 cells were dose and time-dependent based on MTT assays, in which saponin S2 exhibited the highest potency with an IC₅₀ of 41.04 µg/mL at 44 hours. Additionally, Annexin V/P1 staining showed more viable cells with polysaccharide treatment than with saponins, indicating that saponins S1 and S2 have more potent in vitro antitumor activity than polysaccharides P1 and P2.

Holothuria edulis was reported to have in vitro anticancer potential, with an aqueous fraction showing strong cytotoxic effects against the human HL-60 leukemia cell lines (Wijesinghe et al. 2013). The anticancer and cytotoxic activities of a diethyl etheric extract from the H. leucospilota body wall were found to prevent the proliferation of human oral epidermoid carcinoma cells (KB) at a concentration of 500 µg/mL (Bahroodi et al. 2014). A methanolic extract was also effective at 100 µg/mL and 500 µg/mL. Overall, this work revealed that the body wall of H. leucospilota had a strong cytotoxic effect on normal cell lines (human embryonic kidney cells) and thus could be a potent cytotoxic; however, these extracts did not show significant therapeutic value against KB cells.

A methanolic extract of H. atra showed antiproliferative activities against HeLa and MCF-7 cell lines (Dhinakara and Lipton 2014). An ethanol extract of H. atra had strong anticancer activity (IC₅₀ = 12.16 µL/mL) against Supris clone-1 (SP-C1) cells derived from a cloned lymphadenopathy of patients with oral squamous cell carcinoma (Satari et al. 2017). In contrast, hexane, ethyl acetate, and butanol fractions showed no cytotoxic activities in this study.

Organic extracts of H. edulis and S. horrens were tested for cytotoxic effects against two human cancer cell lines, esophageal carcinoma (TE-1) and non-small cell lung carcinoma (A549) (Althunibat et al. 2013). The organic extract of H. edulis exhibited cytotoxicity against TE-1 cancer cells (IC₅₀ = 17 µg/mL), while the S. horrens organic extract was cytotoxic in TE-1 and A549 cancer cells (IC₅₀ = 4.0 µg/mL and 15.5 µg/mL, respectively).

The anticancer potential of H. leucospilota saponin against the B16F10 melanoma cell line was investigated alone and in combination with the chemotherapy drug, dacarbazine (Baharara et al. 2016). The saponin, dacarbazine, and saponin-dacarbazine combination inhibited proliferation in a dose and time-dependent manner, with IC₅₀ values of 10, 1400, and 4 + 1200 µg/mL respectively. Notably, the saponin extract induced intrinsic apoptosis via upregulation of caspase-3 and caspase-9, suggesting its potential as a new treatment modality for metastatic melanoma.

Osteosarcoma is the most common malignant bone cancer in children and adolescents (Kansara et al. 2014) and is particularly difficult to cure due to the incidence of malignant metastasis. New therapeutic approaches are urgently required to prevent metastasis and improve the outcomes for osteosarcoma patients. The anti-metastatic capacity of fucoidan isolated from Cucumaria frondosa against osteosarcoma cells (U2OS) has been investigated using cell adhesion, U2OS cell migration, and transwell migration assays(Zhang et al. 2020). The C. frondosa fucoidan was found to prevent U2OS cell adhesion to fibronectin and inhibit U2OS cell migration significantly, in particular, impairing the migration capacity, distance, and velocity. C. frondosa fucoidan impaired the dynamic remodeling of the cytoskeleton, possibly by suppressing the phosphorylation of focal adhesion kinase and paxillin and by activating the Rac1/PAK/UMK1/cofilin signaling axis.

Nine new sulfated triterpene glycosides, magnumosides A₁ (4), A₂ (5), A₃ (6), A₄ (7), B₁ (8), B₂ (9), C₁ (10), C₂ (11), and C₄ (12), and colohiroside B₂ (13) were successfully isolated from Massinium magnum collected from Vietnamese shallow waters (Fig. 2) (Silchenko et al. 2017). The cytotoxic activities of (4)–(11) were demonstrated against mouse spleen lymphocytes, the ascites form of mouse Ehrlich carcinoma cells, human colorectal carcinoma DLD-1 cells, and hemolytic cells. The erythrocytes were more sensitive to the glycosides than the splenocytes and cancer cells. Interestingly, (6) and (10) significantly inhibited colony formation and decreased the size of DLD-1 cancer cell colonies at non-cytotoxic concentrations. In addition, subtoxic doses of (6) and (10) – (12) manifested synergistic effects with radioactive irradiation on the proliferation of DLD-1 cells.

The presence of bioactive compounds with anticancer potential in sea cucumbers make them an important marine invertebrate for further exploration into the development of novel cytotoxics.

Bacteria are responsible for a vast number of human ailments and diseases, including diarrhea, cholera, pneumonia, tetanus, leprosy, typhus, tuberculosis, diphtheria, and dysentery. Antibiotics are useful against these microorganisms but their misuse and overuse have resulted in the evolution of multiple antibiotic-resistant bacterial strains. The failure of modern synthetic antibiotics has prompted the search for new compounds derived from natural resources.

An ethyl acetate extract of H. leucospilota body wall showed strong antibacterial activity against Staphylococcus aureus with a minimum inhibitory concentration (MIC) of 0.250 mg/mL (Darya et al. 2020). A chloroform extract of H. nobilis was found to display antibacterial activity against Escherichia coli and was also a toxic (acute) and potent antitumor agent than several standard chemotherapeutics, such as Ara-C (Layson et al. 2014).

The antibiotic activity of four Indonesian sea cucumber species, S. chloronotus, S. herrmanni, Bohadschia argus, and B. marmorata, was tested against six bacterial strains (Staphylococcus aureus, Escherichia coli, Pseudomonas sp., Vibrio vulnificus, V. anguillarum, and Bacillus subtilis) (Pringgenies 2013). Bohadschia argus and B. marmorata were active against all the bacteria, while preliminary results with S. herrmanni and S. chloronotus suggested activity against S. aureus, E. coli, Pseudomonas sp., and V. vulnificus. A methanolic extract of S. herrmanni was found to display antibacterial activity against S. aureus, B. subtilis, and V. eltor (Rasyid 2012). Stichopus herrmanni has also shown significant antifungal activity against Aspergillus niger, with MICs ranging from 3–15 µg/mL. The most potent antifungal activity (18 µg/mL) against A. niger was found in a methanol extract of S. herrmanni body wall, resulting in a zone of inhibition of 38 mm (Sarhadizadeh et al. 2014).

The antibacterial activity of aqueous extracts from different tissues of Isostichopus badionotus was evaluated, with muscle and respiratory tract extracts displaying potent activity (Moguel-Salazar et al. 2013). In particular, high antibacterial activity against V. cholera, E. coli, S. aureus, and P. aeruginosa was observed from the membrane protein fraction, with MICs against V. cholera and S. aureus of 8.4 µg/mL and 37.4 µg/mL, respectively. Interestingly, this activity was resistant to both heat and proteinase K, indicating that the active compound is non-protein in origin and favors the use of I. badionotus as a potential source of novel antibiotics.

The antibacterial and antifungal activities of sea cucumber extracts suggest that this marine organism holds great potential for the discovery and development of future antibiotics.

The anti-inflammatory activities of H. poli have been investigated, with its aqueous fraction decreasing the levels of the inflammatory markers interleukin (IL)-6, nitric oxide, and MMP-9 in mouse mammary SCP2 cells (Kareh et al. 2018). The aqueous fraction of H. poli was also found to decrease IL-1 levels induced by phorbol-12-myristate-13-acetate–activated THP-1 human monocytes.

A methanolic extract of H. leucospilota muscular body wall was found to display anti-inflammatory activities in albino rats (Hadi et al. 2020). Holothuria leucospilota samples were dried and extracted with hexane, ethyl acetate, and methanol and examined in vitro via lipoxygenase enzyme inhibition, resulting in inhibition values of 9.74 ± 1.57%, 12.92 ± 1.22%, and 43.75 ± 2.83%, respectively. The methanol extract was notably potent, displaying anti-inflammatory effects superior to acetylsalicylic acid. The anti-inflammatory activities of H. forskali and P. tremulus extracts have also been investigated (Mena-Bueno et al. 2016). Bioavailable compounds in H. forskali decreased intercellular adhesion molecule expression in subcutaneous adipose tissue (p < 0.05) and those in P. tremulus reduced vascular cell adhesion protein (p < 0.01) and IL-6 (p < 0.05) expression levels in endothelial cells. It should be noted that this effect was observed in epicardial adipose tissue.

The in vitro anti-inflammatory potential of H. edulis was evaluated via the determination of a pro-inflammatory mediator (Wijesinghe et al. 2013). An ethyl acetate fraction exhibited profound anti-inflammatory potential in lipopolysaccharide-stimulated RAW 264.7 macrophages, dose-dependently inhibiting nitric oxide production and significantly downregulating inducible nitric oxide synthase and cyclooxygenase-2 expression, prostaglandin E2 release, and pro-inflammatory cytokine tumor necrosis factor-α, IL-1β and IL-6. These multiple activities suggest that the ethyl acetate fraction of H. edulis could contain functional ingredients for use in industrial applications.

Apostichopus japonicus extracts have been shown to ameliorate allergic airway inflammation via CD4⁺CD25⁺Foxp3⁺T cell activation and recruitment to the lung (Lee et al. 2017). This study investigated which components of A. japonicus contributed to the amelioration of airway inflammation using n-hexane fractionation to separate the components into three phases (n-hexane, alcohol, and solid). The three phases were evaluated the ability to elevate IL-10 expression in splenocytes and ameliorate symptoms in mice with ovalbumin/alum-induced asthma. The n-hexane treatment resulted in a significant increase in IL-10 expression and ameliorated asthma symptoms. Notably, approximately 47 fatty acids were identified in this phase.

Sulfated polysaccharides were successfully isolated from Holothuria nobilis, H. edulis, and Apostichopus japonicus (Luo et al. 2013). Nuclear magnetic resonance analysis indicated that sulfated fucans and fucosylated chondroitin sulfates were present in all species, while neutral glycans were specific to H. edulis. The same polysaccharide type in different sea cucumber species had similar anticoagulant activities, while the different glycans functioned significantly different, likely due to differences in their average molecular weight, monosaccharide composition, and electric charge. The fucosylated chondroitin sulfates had stronger anticoagulant activities than the sulfated fucans, while the neutral glycan had no activity, which was expected owing to the absence of a sulfate.

Saponin-enriched Pearsonothuria graeffei Semper extract was found to exhibit antiobesity activity via inhibition of pancreatic lipase activity and upregulation of LXR-β signaling (Guo et al. 2015). Crude P. graeffei Semper extract inhibited pancreatic lipase activity by 36.44% of the control at 0.5 µg/mL. The optimal active extract (SC-3) and echinoside A inhibited pancreatic lipase with IC₅₀ values of 2.86 µg/mL and 0.076 µM, respectively. Approximately 0.1% SC-3 reduced body weight (23.0 ± 62 versus 26.3 ± 0.76 g), serum total cholesterol (2.46 ± 0.04 versus 2.83 ± 0.12 mmol/L), serum triglyceride (0.19 ± 0.08 versus 0.03 ± 0.03 mmol/L), low-density lipoprotein cholesterol (0.48 ± 0.02 versus 0.51 ± 0.02 mmol/L), liver total cholesterol (1.19 ± 0.17 versus 1.85 ± 0.13 mmol/L), and triglyceride (6.18 ± 0.92 versus 10.87 ± 0.97 mmol/mg) contents of obese C57BL/6 mice on a high-fat diet. These results indicate that P. graeffei Semper may be useful for developing antiobesity and antihyperlipidemic drugs in the future.

There is growing interest in food components that may help prevent lifestyle-related diseases. The effects of P. graeffei saponins on high-fat diet-induced obesity, insulin resistance, and fatty liver in C57BL/6 mice have been investigated (Hu et al. 2012). The mice were fed a high-fat diet containing either 0.03% or 0.1% saponin sea cucumber for 8 weeks. Both doses exhibited weight-loss effects and significantly decreased adipose tissue weight in both visceral and subcutaneous depots. Moreover, 0.1% saponin sea cucumber dramatically decreased hepatic triglyceride and total cholesterol accumulation. Mice fed 0.1% saponin sea cucumber also showed significantly reduced serum glucose and insulin levels and a lower homeostatic model assessment for insulin resistance index (HOMA-IR). Dietary saponin sea cucumber also prevented adipokine imbalance by increasing adiponectin production and decreasing tumor necrosis factor-α levels associated with a high-fat diet.

Fucoidan extracted from A. molpadioides has been shown to significantly increase glucose consumption and improve insulin resistance both in vivo and in vitro (Xu et al. 2015). Insulin-resistant mouse models were established by feeding the mice a high-fat, high-fructose diet. Treatment with A. molpadioides fucoidan increased serum insulin levels, decreased HOMA-IR, reduced fasting blood glucose levels, and improved oral glucose tolerance, revealing that it could mitigate insulin resistance in vivo. Combination treatment with A. molpadioides fucoidan and rosiglitazone further reverted insulin resistance.

The antiviral activity of sea cucumbers against human rotavirus A was investigated in cell culture using an aqueous Patallus mollis extract (Garcia-Candela et al. 2019). Patallus mollis is endemic to the coasts of Chile and Peru. The mean extract cytotoxic concentration used in the antiviral assay was 27,042.10 µg/mL, with every concentration used resulting in 99.9% inhibition of antiviral activity. To determine its mode of action, cells were treated with the P. mollis extracts during different phases of the viral infection cycle. The extract was found to inhibit 99% of the virus during absorption and viral inactivation phases.

In vitro studies with Stichopus spp. extracts were performed to elucidate their effects on cell viability and function (Shahrulazua et al. 2013). An inverse relationship was observed between Stichopus spp. extract concentration and osteoblast cell viability (p < 0.001), with only 1 mg/mL significantly promoting cell viability at day 3 of incubation. Osteoblast cell function tended to increase with 50 mg/mL and 10 mg/mL Stichopus spp. extracts, although this varied with different incubation periods.

Although many marine-derived compounds have found use in the pharmaceutical industry, with some already on the market, their use in the development of natural cosmetics is underexplored compared to their terrestrial-derived counterparts. However, many cosmetic companies have recently begun turning their attention to the sea for compounds with potential for use in anti-aging, skin whitening, moisturizers, and photoprotection. With growing investigations of small molecules, enzymes, and biopolymers from the marine environment, it is expected that the era of “blue cosmetics” will soon dominate the sector (Alparslan et al. 2018). This expectation is not without reason, given the increasing public awareness of the importance of cosmetics in life. Additionally, the potential for the utilization of active compounds from marine organisms, particularly sea cucumbers is very promising.

Antioxidants are essential to preventing ultra violet-induced reactive oxygen species, such as hydroxyl radical, superoxide anion, and hydrogen peroxide, from attacking membrane lipids, DNA, and protein. The oxidation of membrane lipids is one of the primary causes of a reduced youthful appearance, therefore, preventing the formation of reactive oxygen species is essential to maintaining wrinkle-free skin. Antioxidants protect human skin from the pro-oxidative environment to which it is exposed in the form of ultraviolet radiation, air pollutants, and smoke (Alves et al. 2020).

Sea cucumbers are reported to be a potential source of natural antioxidants. Holothuria leucospilota protein hydrolysate obtained using flavourzyme and alcalase enzymes showed concentration-dependent antioxidant activity. The flavourzyme preparation provided higher activity than the alcalase in the 2,2-diphenyl-1-picrylhydrazyl (DPPH)-free radical control, with concentrations of 5 mg/mL and 2 mg/mL (Safari and Yaghoudzadeh 2020). The antioxidant activities of aqueous and organic extracts of S. horrens and H. edulis were evaluated (Althunibat et al. 2013). Stichopus horrens aqueous and organic extracts inhibited 79.62% and 46.66% of ß-carotene oxidation by linoleate free radical, respectively. H. edulis aqueous and organic extracts exhibited DPPH radical scavenging with IC₅₀ = 2.0 mg/mL and 8.73 mg/mL, respectively.

The antioxidant activities of fresh and rehydrated H. parva were equivalent to 0.063 and 0.060 mg vitamin C/g dry sample (IC₅₀ = 5.26 µg/mL and 4.14 µg/mL), respectively. The flavonoid content of fresh and rehydrated samples was equivalent to 3.86 and 5.02 mg quercetin/g dry samples, respectively. The total phenolic content of the fresh and rehydrated sample was equivalent to 0.22 and 0.19 mg gallic acid/g dry sample, respectively (Diba et al. 2017).

Apostichopus japonicus was hydrolyzed by papain, trypsin, pepsin, acid protease, and neutral protease to obtain five peptide fractions, for which their antioxidant activities were evaluated by hydroxyl radical (•OH) and superoxide anion (•O₂–) scavenging (Zhou et al. 2011). The trypsinized peptides exhibited the highest antioxidant activity. Apostichopus japonicas hydrolysates increased survival rate, inhibited the accumulation of reactive oxygen species, upregulated total superoxide dismutase and catalase activities, and reduced lipid peroxidation malondialdehyde content in a Caenorhabditis elegans model undergoing increased oxidative stress (Guoet et al. 2020).

A methanolic extract of S. herrmanni collected from Indonesian waters was examined for antioxidant activity using DPPH giving an IC₅₀ = 65.08 µg/mL (Rasyid 2012). Stichopus vastus collagen was successfully hydrolyzed by trypsin and was found to rich in alanine, glycine, proline, glutamine, and hydroxyproline residues and exhibited excellent radical-scavenging activity, indicating that collagen hydrolysates from S. vastus can be used as functional ingredients in nutraceutical and food products (Abedin et al. 2014).

Holothuria scabra is one of the most commercially valuable species. Its antioxidant activity was measured using DPPH and Folin-Ciocalteu reagent (Nobsathian et al. 2017). The crude methanol extract and purified friedelin (14), 3-hydroxybenzaldehyde (15), and 4-hydroxybenzaldehyde (16) (Fig. 3) isolated from this species strongly inhibit free radicals with effective concentrations (EC₅₀s) similar to ascorbic acid (14.90 ± 5.5 × 10^-3). The total phenolic content was 30.52 ± 0.21 GAE/g dry weight. These results indicate that H. scabra could be used to develop nutraceuticals for patients with cardiovascular symptoms. It may also support antioxidant substances involved in preventing free radical damage, such as quercetin, a flavonoid found in onions, as well as preserve blood pressure, vascular function, heart rate, and vascular responsiveness to stress.

A comparison of the radical scavenging activity of H. leucospilota, H. atra, H. fuscocinerea, and H. excellens using DPPH found H. atra extract to have the strongest DPPH scavenging activity (13.14 ± 2.17%) at a concentration of 0.1 mg/mL. H. atra can be considered as a natural antioxidant source for pharmaceutical, food (Pangestuti et al. 2016), and cosmetic industries.

Figure 2. 

Structures of magnumosides A₁ (4), A₂ (5), A₃ (6), A₄ (7), B₁ (8), B₂ (9), C₁ (10), C₂ (11), C₄ (12), and colohiroside B₂ (13).

Figure 3. 

Structures of friedelin (14), 3-hydroxybenzaldehyde (15), and 4-hydroxybenzaldehyde (16).

Research related to the treatment of aging and age-related diseases is a focus of public health. A. japonicas protein hydrolysate was found to increase age pigment and extend lifespan without reducing food intake, body length, or blood size of nematodes, demonstrating its capacity to delay physiological aging (Guo et al. 2020). The peptide profile and antiaging activity of purified C. frondosa hydrolysate prepared by enzymatic hydrolysis and ultrafiltration were examined in vivo in fruit flies and mice with age-related neurodegenerative disorders associated with D-galactose-induced aging (Lin et al. 2018). California frondosa hydrolysate significantly prolonged the lifespan of fruit flies and ameliorated learning and memory deficits in mice experiencing D-galactose-induced aging. The mechanism underlying these protective effects might be related to upregulation of Klotho expression, inhibition of lipid peroxidation and protein oxidation, increased superoxide dismutase and glutathione peroxidase activities, and downregulation of acetylcholinesterase activity. This work suggests that C. frondosa hydrolysate could contain health-promoting ingredients for combating aging and age-related diseases.

The boiling process, one of the stages in the production of dried sea cucumbers, generates liquid extracts that are largely discarded without considering the therapeutic and economic value of their contents. In addition, this could contribute to environmental pollution.

Glycoprotein fractions from the liquid extract of boiled A. japonicas were investigated for their efficacy in skin whitening and wrinkle improvement and their effects on tyrosine and elastase inhibitory activities (Kim et al. 2016). Fractions greater and less than 50 kDa enhanced tyrosinase and elastase inhibitory activities by 50.84% and 28.79%, respectively, with the concentration of the > 50 kDa fractions showing a significant correlation with elastase inhibitory (R² = 0.983) and tyrosinase inhibitory (R² = 0.968) efficacy. This suggests that the glycoprotein fractions could be useful as cosmetic ingredients for skin whitening and wrinkle improvement.

The development of moisturizing cosmetic products from marine organisms, particularly sea cucumbers, continues to be pursued. Pepsin-solubilized collagen extracted from H. cinerascens has been compared with that from the skin of tilapia and pig, all of which exhibited better moisture absorption and moisture capacity than glycerol (Li et al. 2019). The dominant amino acids of the three collagens were proline (9–12%), glycine (31%), and alanine (10–12%). The collagen molecules of H. cinerascens were found to be rich in hydrophilic groups, which could prove useful in cosmetic formulations.

The exploitation of sea cucumbers must be carefully considered, as their numbers in the wild have been reduced. With the widespread dissemination and commercialization of their biological activity, a method guaranteeing sea cucumber availability, such as cultivation, is important.