Browse > Article
http://dx.doi.org/10.1186/s41240-017-0071-y

Biological activities and biomedical potential of sea cucumber (Stichopus japonicus): a review  

Oh, Gun-Woo (Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University)
Ko, Seok-Chun (Marine-Integrated Bionics Research Center, Pukyong National University)
Lee, Dong Hee (Gyeongbuk Institute for Bio industry)
Heo, Soo-Jin (Jeju International Marine Science Center for Research & Education, Korea Institute of Ocean Science and Technology)
Jung, Won-Kyo (Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University)
Publication Information
Fisheries and Aquatic Sciences / v.20, no.11, 2017 , pp. 28.1-28.17 More about this Journal
Abstract
Members of the phylum Echinodermata, commonly known as echinoderms, are exclusively marine invertebrates. Among the Echinodermata, sea cucumber belongs to the family Holothuroidea. The sea cucumber Stichopus (Apostichous) japonicus (Selenka) is an invertebrate animal inhabiting the coastal sea around Korean, Japan, China, and Russia. Sea cucumber has a significant commercial value, because it contains valuable nutrients such as vitamins and minerals. They possess a number of distinctive biologically and pharmacologically important compounds. In particular, the body wall of sea cucumber is a major edible part. It consists of peptide, collagen, gelatin, polysaccharide, and saponin, which possess several biological activities such as anti-cancer, anti-coagulation, anti-oxidation, and anti-osteoclastogenesis. Furthermore, the regenerative capacity of sea cucumber makes it a medically important organism. This review presents the various biological activities and biomedical potential of sea cucumber S. japonicus.
Keywords
Biomedical potential; Biological activities; Marine invertebrate; Sea cucumber; Stichopus japonicus;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Ale MT, Meyer AS. Fucoidans from brown seaweeds: An update on structures, extraction techniques and use of enzymes as tools for structural elucidation. RSC Adv. 2013;3:8131-41.   DOI
2 Ale MT, Mikkelsen JD, Meyer AS. Important determinants for fucoidan bioactivity: a critical review of structure-function relations and extraction methods for fucose-containing sulfated polysaccharides from brown seaweeds. Mar Drugs. 2011;9:2106-30.   DOI
3 Alves RRN, Rosa IL. Animals in traditional folk medicine: implications for conservation. Berlin Heidelberg: Springer; 2012.
4 Anderson SC, Flemming JM, Watson R, Lotze HK. Serial exploitation of global sea cucumber fisheries. Fish Fish. 2011;12:317-39.   DOI
5 Arron JR, Choi Y. Osteoimmunology: bone versus immune system. Nature. 2000; 408:535-6.   DOI
6 Bordbar S, Anwar F, Saari N. High-value components and bioactives from sea cucumbers for functional foods-a review. Marine Drugs. 2011;9:1761-805.   DOI
7 Aydin M, Sevgili H, Tufan B, Emre Y, Kose S. Proximate composition and fatty acid profile of three different fresh and dried commercial sea cucumbers from Turkey. Int J Food Sci Technol. 2011;46:500-8.   DOI
8 Bai Y, Zhang L, Liu S, Ru X, Xing L, Cao X, Zhang T, Yang H. The effect of salinity on the growth, energy budget and physiological performance of green, white and purple color morphs of sea cucumber, Apostichopus japonicus. Aquaculture. 2015;437:297-303.   DOI
9 Bickers DR, Athar M. Oxidative stress in the pathogenesis of skin disease. J Invest Dermatol. 2006;126:2565-75.   DOI
10 Cabiscol E, Tamarit J, Ros J. Oxidative stress in bacteria and protein damage by reactive oxygen species. Int Microb. 2000;3:3-8.
11 Cai Q, Yang J, Bei J, Wang S. A novel porous cells scaffold made of polylactide-dextran blend by combining phase-separation and particle-leaching techniques. Biomaterials. 2002;23:4483-92.   DOI
12 Cao RA, Surayot U, You S. Structural characterization of immunostimulating protein-sulfated fucan complex extracted from the body wall of a sea cucumber, Stichopus japonicus. Int J Biol Macromol. 2017;99:539-48.   DOI
13 Cao X, Yeo G, Muotri AR, Kuwabara T, Gage FH. Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci. 2006;29:77-103.   DOI
14 Chandika P, Ko S, Jung W. Marine-derived biological macromolecule-based biomaterials for wound healing and skin tissue regeneration. Int J Biol Macromol. 2015;77:24-35.   DOI
15 Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M, Group SNTR. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002;359:2072-7.   DOI
16 Li L, Li Q. Effects of stocking density, temperature, and salinity on larval survival and growth of the red race of the sea cucumber Apostichopus japonicus (Selenka). Aquacult Int. 2010;18:447-60.   DOI
17 Li Y, Wang L, Liu Z, Li C, Xu J, Gu Q, Xu J. Predicting selective liver X receptor $\beta$ agonists using multiple machine learning methods. Mol BioSyst. 2015;11:1241-50.   DOI
18 Li Z, Ramay HR, Hauch KD, Xiao D, Zhang M. Chitosan-alginate hybrid scaffolds for bone tissue engineering. Biomaterials. 2005;26:3919-28.   DOI
19 Chen WC, Tseng TS, Hsiao NW, Lin YL, Wen ZH, Tsai CC, Lee YC, Lin HH, Tsai KC. Discovery of highly potent tyrosinase inhibitor, T1, with significant antimelanogenesis ability by zebrafish in vivo assay and computational molecular modeling. Sci Rep. 2015;5:7995.   DOI
20 Chen Z, Wang P, Wei B, Mo X, Cui F. Electrospun collagen-chitosan nanofiber: A biomimetic extracellular matrix for endothelial cell and smooth muscle cell. Acta Biomater. 2010;6:372-82.   DOI
21 Choi J, Seo JY, Lee SM. Effects of sources and levels of dietary carbohydrate on growth and body composition of juvenile sea cucumbers, Apostichopus japonicus. Fish Aquatic Sci. 2009;12:203-8.   DOI
22 Cui C, Cui N, Wang P, Song S, Liang H, Ji A. Sulfated polysaccharide isolated from the sea cucumber Stichopus japonicus against PC12 hypoxia/reoxygenation injury by inhibition of the MAPK signaling pathway. Cell Mol Neurobiol. 2015;35:1081-92.   DOI
23 Cui C, Cui N, Wang P, Song S, Liang H, Ji A. Neuroprotective effect of sulfated polysaccharide isolated from sea cucumber Stichopus japonicus on 6-OHDAinduced death in SH-SY5Y through inhibition of MAPK and NF-${\kappa}B$ and activation of PI3K/Akt signaling pathways. Biochem Bioph Res Co. 2016a;470:375-83.   DOI
24 Cui C, Wang P, Cui N, Song S, Liang H, Ji A. Stichopus japonicus polysaccharide, fucoidan, or heparin enhanced the SDF-$1{\alpha}$/CXCR4 axis and promoted NSC migration via activation of the PI3K/Akt/FOXO3a signaling pathway. Cell Mol Neurobiol. 2016b;36:1311-29.   DOI
25 Lu Y, Zhang BY, Dong Q, Wang BL, Sun XB. The effects of Stichopus japonicus acid mucopolysaccharide on the apoptosis of the human hepatocellular carcinoma cell line HepG2. Am J Med Sci. 2010;339:141-4.   DOI
26 Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443:787-95.   DOI
27 Liu D, Liang L, Regenstein JM, Zhou P. Extraction and characterisation of pepsinsolubilised collagen from fins, scales, skins, bones and swim bladders of bighead carp (Hypophthalmichthys nobilis). Food Chem. 2012a;133:1441-8.   DOI
28 Liu X, Sun Z, Zhang M, Meng X, Xia X, Yuan W, Xue F, Liu C. Antioxidant and antihyperlipidemic activities of polysaccharides from sea cucumber Apostichopus japonicus. Carbohyd Polym. 2012b;90:1664-70.   DOI
29 Machado M, Nassor N, Bajcar JM, Guzzo GC, Einarson TR. Sensitivity of patient outcomes to pharmacist interventions. Part III: systematic review and metaanalysis in hyperlipidemia management. Ann Pharmacother. 2008;42:1195-207.   DOI
30 Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. Arterioscl Throm Vas. 2007;27:1687-93.   DOI
31 Li B, Lu F, Wei X, Zhao R. Fucoidan: structure and bioactivity. Molecules. 2008;13:1671-95.   DOI
32 Maddika S, Ande SR, Panigrahi S, Paranjothy T, Weglarczyk K, Zuse A, Eshraghi M, Manda KD, Wiechec E, Los M. Cell survival, cell death and cell cycle pathways are interconnected: implications for cancer therapy. Drug Resist Updat. 2007;10:13-29.   DOI
33 Moller DE. New drug targets for type 2 diabetes and the metabolic syndrome. Nature. 2001;414:821-7.   DOI
34 Maertens J, Raad I, Petrikkos G, Boogaerts M, Selleslag D, Petersen FB, Sable CA, Kartsonis NA, Ngai A, Taylor A. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis. 2004;39:1563-71.   DOI
35 Marcus A, Gowen BG, Thompson TW, Iannello A, Ardolino M, Deng W, Wang L, Shifrin N, Raulet DH. Recognition of tumors by the innate immune system and natural killer cells. Adv Immunol. 2014;122:91.
36 Mestechkina N, Shcherbukhin V. Sulfated polysaccharides and their anticoagulant activity: A review. Appl Biochem Micro. 2010;46:267-73.   DOI
37 Muralidharan N, Shakila RJ, Sukumar D, Jeyasekaran G. Skin, bone and muscle collagen extraction from the trash fish, leather jacket (Odonus niger) and their characterization. J Food Sci Tech. 2013;50:1106-13.   DOI
38 Nguyen TH, Um BH, Kim SM. Two Unsaturated Fatty Acids with Potent ${\alpha}$-Glucosidase Inhibitory Activity Purified from the Body Wall of Sea Cucumber (Stichopus japonicus). J Food Sci. 2011;76:H208-14.   DOI
39 Oh CT, Kwon TR, Jang YJ, Yoo KH, Kim BJ, Kim H. Inhibitory effects of Stichopus japonicus extract on melanogenesis of mouse cells via ERK phosphorylation. Mol Med Rep. 2017;16:1079-86.   DOI
40 Oh GW, Ko SC, Heo SY, Nguyen VT, Kim G, Jang CH, Park WS, Choi IW, Qian ZJ, Jung WK. A novel peptide purified from the fermented microalga Pavlova lutheri attenuates oxidative stress and melanogenesis in B16F10 melanoma cells. Process Biochem. 2015;50:1318-26.   DOI
41 Dong P, Xue CH, Yu LF, XU J, Chen SG. Determination of triterpene glycosides in sea cucumber (stichopus japonicus) and its related products by highperformance liquid chromatography. J Agric Food Chem. 2008;56:4937-42.   DOI
42 Cui C, Wang P, Cui N, Song S, Liang H, Ji A. Sulfated polysaccharide isolated from the sea cucumber Stichopus japonicus promotes the SDF-$1{\alpha}$/CXCR4 axisinduced NSC migration via the PI3K/Akt/FOXO3a, ERK/MAPK, and NF-${\kappa}B$ signaling pathways. Neurosci Lett. 2016c;16:57-64.
43 Cui FX, Xue CH, Li ZJ, Zhang YQ, Dong P, Fu XY, Gao X. Characterization and subunit composition of collagen from the body wall of sea cucumber Stichopus japonicus. Food Chem. 2007;100:1120-5.   DOI
44 Cuong NX, Nhiem NX, Thao NP, Nam NH, Dat NT, Anh HLT, Van Kiem P, Van Minh C, Won JH, Chung WY. Inhibitors of osteoclastogenesis from Lawsonia inermis leaves. Bioorg Med Chem Lett. 2010;20:4782-4.   DOI
45 Dong Y, Dong S, Tian X, Wang F, Zhang M. Effects of diel temperature fluctuations on growth, oxygen consumption and proximate body composition in the sea cucumber Apostichopus japonicus Selenka. Aquaculture. 2006;255:514-21.   DOI
46 Du H, Bao Z, Hou R, Wang S, Su H, Yan J, Tian M, Li Y, Wei W, Lu W. Transcriptome sequencing and characterization for the sea cucumber Apostichopus japonicus (Selenka, 1867). PLoS One. 2012;7:e33311.   DOI
47 Duan X, Zhang M, Mujumdar AS, Wang S. Microwave freeze drying of sea cucumber (Stichopus japonicus). J Food Eng. 2010;96:491-7.   DOI
48 Park SY, Lim HK, Lee S, Hwang HC, Cho SK, Cho M. Pepsin-solubilised collagen (PSC) from Red Sea cucumber (Stichopus japonicus) regulates cell cycle and the fibronectin synthesis in HaCaT cell migration. Food Chem. 2012;132:487-92.   DOI
49 Okorie OE, Ko SH, Go S, Lee S, Bae JY, Han K, Bai SC. Preliminary study of the optimum dietary ascorbic acid level in sea cucumber, Apostichopus japonicus (Selenka). J World Aquacult Soc. 2008;39:758-65.   DOI
50 Park SY, Lim HK, Lee S, Cho SK, Park S, Cho M. Biological effects of various solvent fractions derived from Jeju Island red sea cucumber (Stichopus japonicas). J Korean Soc Appl Biol Chem. 2011;54:718-24.
51 Pati F, Adhikari B, Dhara S. Isolation and characterization of fish scale collagen of higher thermal stability. Bioresour Technol. 2010;101:3737-42.   DOI
52 Patterson TF. Advances and challenges in management of invasive mycoses. Lancet. 2005;366:1013-25.   DOI
53 Pederson L, Ruan M, Westendorf JJ, Khosla S, Oursler MJ. Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. Proc Natl Acad Sci U S A. 2008;105:20764-9.   DOI
54 Pfaller MA, Diekema DJ. Epidemiology of invasive mycoses in North America. Crit Rev Microbiol. 2010;36:1-53.   DOI
55 Pfaller MA, Pappas PG, Wingard JR. Invasive fungal pathogens: current epidemiological trends. Clin Infect Dis. 2006;43:S3-S14.   DOI
56 Purcell SW, Conand C, Uthicke S, Byrne M. Ecological roles of exploited sea cucumber. Oceanor Mar Biol. 2016;54:367-86.
57 Qiao Z, Koizumi Y, Zhang M, Natsui M, Flores MJ, Gao L, Yusa K, Koyota S, Sugiyama T. Anti-melanogenesis effect of Glechoma hederacea L. extract on B16 murine melanoma cells. Biosci Biotechnol Biochem. 2012;76:1877-83.   DOI
58 Fang FC. Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat Rev Microbiol. 2004;2:820-32.   DOI
59 Dupont S, Ortega-Martinez O, Thorndyke M. Impact of near-future ocean acidification on echinoderms. Ecotoxicology. 2010;19:449-62.   DOI
60 Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature. 2001;411:342-8.   DOI
61 FAO. Sea cucumbers: A global review of fisheries and trade. Rome: Technical Report 516, Food and Agriculture Organization of the United Nations; 2008.
62 Ferdouse F. World markets and trade flows of sea cucumber/beche-de-mar. In: Advances in sea cucumber aquaculture and management. Rome: Food and Agriculture Organization of the United Nations; 2004. p. 101-16.
63 Gailani D, Renne T. Intrinsic pathway of coagulation and arterial thrombosis. Arterioscl Throm Vas. 2007;27:2507-13.   DOI
64 Gao F, Xu Q, Yang H. Seasonal biochemical changes in composition of body wall tissues of sea cucumber Apostichopus japonicus. Chin J Oceanol Limn. 2011a; 29:252-60.   DOI
65 Gao QF, Wang Y, Dong S, Sun Z, Wang F. Absorption of different food sources by sea cucumber Apostichopus japonicus (Selenka)(Echinodermata: Holothuroidea): evidence from carbon stable isotope. Aquaculture. 2011b; 319:272-6.   DOI
66 Gunn J, Zhang M. Polyblend nanofibers for biomedical applications: perspectives and challenges. Trends Biotechnol. 2010;28:189-97.   DOI
67 Hendry SA, Farnsworth RH, Solomon B, Achen MG, Stacker SA, Fox SB. The Role of the Tumor Vasculature in the Host Immune Response: Implications for Therapeutic Strategies Targeting the Tumor Microenvironment. Front Immunol. 2016;7:621.
68 Schegg B, Hulsmeier AJ, Rutschmann C, Maag C, Hennet T. Core glycosylation of collagen is initiated by two $\beta$ (1-O) galactosyltransferases. Mol Cell Biol. 2009;29:943-52.   DOI
69 Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. Lancet. 2011;377:1276-87.   DOI
70 Saito M, Kunisaki N, Urano N, Kimura S. Collagen as the major edible component of sea cucumber (Stichopus japonicus). J Food Sci. 2002;67:1319-22.   DOI
71 Schepetkin IA, Kirpotina LN, Jakiw L, Khlebnikov AI, Blaskovich CL, Jutila MA, Quinn MT. Immunomodulatory activity of oenothein B isolated from Epilobium angustifolium. J Immunol. 2009;183:6754-66.   DOI
72 Senni K, Pereira J, Gueniche F, Delbarre-Ladrat C, Sinquin C, Ratiskol J, Godeau G, Fischer AM, Helley D, Colliec-Jouault S. Marine polysaccharides: a source of bioactive molecules for cell therapy and tissue engineering. Mar Drugs. 2011;9:1664-81.   DOI
73 Seo JY, Shin IS, Lee SM. Effect of various protein sources in formulated diets on the growth and body composition of juvenile sea cucumber Apostichopus japonicus (Selenka). Aquac Res. 2011;42:623-7.   DOI
74 Sheng X, Li M, Song S, Zhang N, Wang Y, Liang H, Wang W, Ji A. Sulfated polysaccharide isolated from the sea cucumber Stichopus japonicus promotes neurosphere migration and differentiation via up-regulation of N-cadherin. Cell Mol Neurobiol. 2012;32:435-42.   DOI
75 Sheng X, Zhang N, Song S, Li M, Liang H, Zhang Y, Wang Y, Ji A. Morphological transformation and proliferation of rat astrocytes as induced by sulfated polysaccharides from the sea cucumber Stichopus japonicus. Neurosci Lett. 2011;503:37-42.   DOI
76 Xia B, Gao QF, Wang J, Li P, Zhang L, Zhang Z. Effects of dietary carbohydrate level on growth, biochemical composition and glucose metabolism of juvenile sea cucumber Apostichopus japonicus (Selenka). Aquaculture. 2015;448:63-70.   DOI
77 Heo SJ, Hwang JY, Choi JI, Han JS, Kim HJ, Jeon YJ. Diphlorethohydroxycarmalol isolated from Ishige okamurae, a brown algae, a potent ${\alpha}$-glucosidase and ${\alpha}$-amylase inhibitor, alleviates postprandial hyperglycemia in diabetic mice. Eur J Pharmacol. 2009;615:252-6.   DOI
78 Wu B, Xia S, Rahman M, Rajkumar M, Fu Z, Tan J, Yang A. Substituting seaweed with corn leaf in diet of sea cucumber (Apostichopus japonicus): Effects on growth, feed conversion ratio and feed digestibility. Aquaculture. 2015;444:88-92.   DOI
79 Wu HT, Li DM, Zhu BW, Sun JJ, Zheng J, Wang FL, Konno K, Jiang X. Proteolysis of noncollagenous proteins in sea cucumber, Stichopus japonicus, body wall: Characterisation and the effects of cysteine protease inhibitors. Food Chem. 2013;141:1287-94.   DOI
80 Xu X, Yin P, Wan C, Chong X, Liu M, Cheng P, Chen J, Liu F, Xu J. Punicalagin inhibits inflammation in LPS-induced RAW264. 7 macrophages via the suppression of TLR4-mediated MAPKs and NF-${\kappa}B$ activation. Inflammation. 2014;37:956-65.   DOI
81 Yang H, Zhou Y, Zhang T, Yuan X, Li X, Liu Y, Zhang F. Metabolic characteristics of sea cucumber Apostichopus japonicus (Selenka) during aestivation. J Exp Mar Biol Ecol. 2006;330:505-10.   DOI
82 Yang J, Wang Y, Jiang T, Lv L, Zhang B, Lv Z. Depolymerized glycosaminoglycan and its anticoagulant activities from sea cucumber Apostichopus japonicus. Int J Biol Macromol. 2015a;72:699-705.   DOI
83 Yang J, Wang Y, Jiang T, Lv Z. Novel branch patterns and anticoagulant activity of glycosaminoglycan from sea cucumber Apostichopus japonicus. Int J Biol Macromol. 2015b;72:911-8.   DOI
84 Taylor SI. Deconstructing type 2 diabetes. Cell. 1999;97:9-12.   DOI
85 Shida M, Mikami T, Ji T, Kitagawa H. A characteristic chondroitin sulfate trisaccharide unit with a sulfated fucose branch exhibits neurite outgrowth-promoting activity: Novel biological roles of fucosylated chondroitin sulfates isolated from the sea cucumber Apostichopus japonicus. Biochem Bioph Res Co. 2017;487:678-83.   DOI
86 Slominski A, Tobin DJ, Shibahara S, Wortsman J. Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev. 2004;84:1155-228.   DOI
87 Song Y, Jin SJ, Cui LH, Ji XJ, Yang FG. Immunomodulatory effect of Stichopus japonicus acid mucopolysaccharide on experimental hepatocellular carcinoma in rats. Molecules. 2013;18:7179-93.   DOI
88 Tung YT, Chua MT, Wang SY, Chang ST. Anti-inflammation activities of essential oil and its constituents from indigenous cinnamon (Cinnamomum osmophloeum) twigs. Bioresour Technol. 2008;99:3908-13.   DOI
89 Uriarte-Montoya MH, Arias-Moscoso JL, Plascencia-Jatomea M, Santacruz-Ortega H, Rouzaud-Sandez O, Cardenas-Lopez JL, Marquez-Rios E, Ezquerra-Brauer JM. Jumbo squid (Dosidicus gigas) mantle collagen: Extraction, characterization, and potential application in the preparation of chitosan-collagen biofilms. Bioresour Technol. 2010;101:4212-9.   DOI
90 Versteeg HH, Heemskerk JW, Levi M, Reitsma PH. New fundamentals in hemostasis. Physiol Rev. 2013;93:327-58.   DOI
91 Wang J, Wang Y, Tang Q, Wang Y, Chang Y, Zhao Q, Xue C. Antioxidation activities of low-molecular-weight gelatin hydrolysate isolated from the sea cucumber Stichopus japonicus. J Ocean U China. 2010;9:94-8.   DOI
92 Holtkamp AD, Kelly S, Ulber R, Lang S. Fucoidans and fucoidanases-focus on techniques for molecular structure elucidation and modification of marine polysaccharides. Appl Microbiol Biot. 2009;82:1.   DOI
93 Yoon W, Kim M, Koh H, Lee W, Lee N, Hyun C. Effect of Korean red sea cucumber (Stichopus japonicus) on melanogenic protein expression in murine B16 melanoma. Int J Pharmacol. 2010;6:37-42.   DOI
94 Wei YH, Lee HC. Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med. 2002;227:671-82.   DOI
95 Himaya S, Ryu B, Qian ZJ, Kim SK. Sea cucumber, Stichopus japonicus ethyl acetate fraction modulates the lipopolysaccharide induced iNOS and COX-2 via MAPK signaling pathway in murine macrophages. Environ Toxicol Phar. 2010;30:68-75.   DOI
96 Horner PJ, Gage FH. Regenerating the damaged central nervous system. Nature. 2000;407:963-70.   DOI
97 Huang THW, Peng G, Li GQ, Yamahara J, Roufogalis BD, Li Y. Salacia oblonga root improves postprandial hyperlipidemia and hepatic steatosis in Zucker diabetic fatty rats: activation of PPAR-${\alpha}$. Toxicol Appl Pharm. 2006;210:225-35.   DOI
98 Husni A, Jeon JS, Um BH, Han NS, Chung D. Tyrosinase inhibition by water and ethanol extracts of a far eastern sea cucumber, Stichopus japonicus. Food Sci Biotechnol. 2011;91:1541-7.
99 Husni A, Shin IS, You S, Chung D. Antioxidant properties of water and aqueous ethanol extracts and their crude saponin fractions from a far-eastern sea cucumber, Stichopus japonicus. Food Sci Biotechnol. 2009;18:419-24.
100 Ikonen E. Cellular cholesterol trafficking and compartmentalization. Nat Rev Mol Cell Bio. 2008;9:125-38.   DOI
101 Zhang Y, Song S, Liang H, Wang Y, Wang W, Ji A. Enhancing effect of a sea cucumber Stichopus japonicus sulfated polysaccharide on neurosphere formation in vitro. J Biosci Bioeng. 2010a;110:479-86.   DOI
102 Wang Z, Zhang H, Yuan W, Gong W, Tang H, Liu B, Krohn K, Li L, Yi Y, Zhang W. Antifungal nortriterpene and triterpene glycosides from the sea cucumber Apostichopus japonicus Selenka. Food Chem. 2012;132:295-300.   DOI
103 Yu HB, Gao QF, Dong SL, Wen B. Changes in fatty acid profiles of sea cucumber Apostichopus japonicus (Selenka) induced by terrestrial plants in diets. Aquaculture. 2015a;442:119-24.   DOI
104 Yu L, Xue C, Chang Y, Hu Y, Xu X, Ge L, Liu G. Structure and rheological characteristics of fucoidan from sea cucumber Apostichopus japonicus. Food Chem. 2015b;180:71-6.   DOI
105 Zhang Y, Song S, Song D, Liang H, Wang W, Ji A. Proliferative effects on neural stem/progenitor cells of a sulfated polysaccharide purified from the sea cucumber Stichopus japonicus. J Biosci Bioeng. 2010b;109:67-72.   DOI
106 Zheng J, Wu HT, Zhu BW, Dong XP, Zhang MM, Li YL. Identification of antioxidative oligopeptides derived from autolysis hydrolysates of sea cucumber (Stichopus japonicus) guts. Eur Food Res Technol. 2012;234:895-904.   DOI
107 Kaneko M, Kisa F, Yamada K, Miyamoto T, Higuchi R. Structure of a New Neuritogenic-Active Ganglioside from the Sea Cucumber Stichopus japonicus. European J Org Chem. 2003;2003:1004-8.   DOI
108 Ito S. A chemist's view of melanogenesis. Pigment Cell Res. 2003;16:230-6.   DOI
109 Jiang S, Dong S, Gao Q, Wang F, Tian X. Comparative study on nutrient composition and growth of green and red sea cucumber, Apostichopus japonicus (Selenka, 1867), under the same culture conditions. Aquac Res. 2013;44:317-20.   DOI
110 Jo J, Park C, Kim M, Park C. Phylogenetic Analysis of the Three Color Variations of the Sea Cucumber Apostichopus japonicus. J Aquac Res Development. 2016;7:2.
111 Kan-no M, Kijima A. Genetic differentiation among three color variants of Japanese sea cucumber Stichopus japonicus. Fisheries Sci. 2003;69:806-12.   DOI
112 Kariya Y, Mulloy B, Imai K, Tominaga A, Kaneko T, Asari A, Suzuki K, Masuda H, Kyogashima M, Ishii T. Isolation and partial characterization of fucan sulfates from the body wall of sea cucumber Stichopus japonicus and their ability to inhibit osteoclastogenesis. Carbohydr Res. 2004;339:1339-46.   DOI
113 Kazantsev AG, Thompson LM. Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov. 2008;7:854-68.   DOI
114 Kim J, Bentley PJ, Aickelin U, Greensmith J, Tedesco G, Twycross J. Immune system approaches to intrusion detection-a review. Nat Comput. 2007a;6:413-66.   DOI
115 Kim NY, Choi WY, Heo SJ, Kang DH, Lee HY. Anti-skin cancer activities of Apostichopus japonicus extracts from low-temperature ultrasonification process. J Healthc Eng. 2017;2017
116 Ko SH, Go S, Okorie OE, Kim YC, Lee S, Yoo GY, Bai SC. Preliminary Study of the Dietary ${\alpha}$-Tocopherol Requirement in Sea Cucumber, Apostichopus japonicus. J World Aquacult Soc. 2009;40:659-66.   DOI
117 Zhou X, Wang C, Jiang A. Antioxidant peptides isolated from sea cucumber Stichopus japonicus. Eur Food Res Technol. 2012;234:441-7.   DOI
118 Zhu BW, Dong XP, Zhou DY, Gao Y, Yang JF, Li DM, Zhao XK, Ren TT, Ye WX, Tan H. Physicochemical properties and radical scavenging capacities of pepsinsolubilized collagen from sea cucumber Stichopus japonicus. Food Hydrocolloid. 2012;28:182-8.   DOI
119 Zohdi RM, Zakaria ZAB, Yusof N, Mustapha NM, Abdullah MNH. Sea cucumber (Stichopus hermanii) based hydrogel to treat burn wounds in rats. J Biomed Mater Res B. 2011;98:30-7.
120 Kim R, Emi M, Tanabe K. Cancer immunoediting from immune surveillance to immune escape. Immunology. 2007b;121:1-14.   DOI
121 Lee MH, Kim YK, Moon HS, Kim KD, Kim GG, Cho HA, Yoon NY, Sim KB, Park HY, Lee DS. Comparison on proximate composition and nutritional profile of red and black sea cucumbers (Apostichopus japonicus) from Ulleungdo (Island) and Dokdo (Island). Korea Food Sci Biotechnol. 2012;21:1285-91.   DOI