Physicochemical and biological activities of polysaccharides from the waste residue of sea cucumber peptide production

Main Article Content

Ruicong Zhang
Rui Liu
Yongde Chen
Tao Wu
Wenjie Sui
Min Zhang


anti-tumour activities, sea cucumber peptide, sea cucumber polysaccharides, waste residue


This study was to investigate the physicochemical and biological activities of sea cucumber polysaccharides extracted from waste residue of peptide production (SCRP). The monosaccharide composition of SCRP was 20.03% mannose, 19.56% glucose, 18.63% galactose, 25.94% arabinose and 15.82% fucose with the Mw and Mn of SCRP of 57.5 and 51.3 kDa. The intrinsic viscosity of SCRP was 8.9 mL/mg with a liquid-like rheological behaviour. Two main endothermic peak temperatures of the SCRP sample were 85.03 and 231.80°C. SCRP rendered the early apoptosis of cells, as well as induced the loss of mitochondrial transmembrane potential and increase the reactive oxygen species (ROS) level with a concentration-dependence manner. The results implied that a by-product SCRP could be extracted from the waste residue during peptide production, and exhibited inhibitory effects against MDA-MB-231 cells.

Abstract 915 | PDF Downloads 480 HTML Downloads 684 XML Downloads 19


Albano, R. and Mourão, P., 1986. Isolation, fractionation, and preliminary characterization of a novel class of sulfated glycans from the tunic of Styela plicata (Chordata Tunicata). Journal of Biological Chemistry 261: 758–765. PMid: 2867092

Atabani, A.E., Shobana, S., Mohammed, M.N., Uguz, G., Kumar, G., Arvindnarayan, S., Aslam, M. and Al-Muhtaseb, A.H., 2019. Integrated valorization of waste cooking oil and spent coffee grounds for biodiesel production: blending with higher alcohols, FT-IR, TGA, DSC and NMR characterizations. Fuel 244: 419–430. 10.1016/j.fuel.2019.01.169

Chen, W., Zhao, Z., Li, L., Wu, B., Chen, S.F., Zhou, H., Wang, Y. and Li, Y.Q., 2018. Hispolon induces apoptosis in human gastric cancer cells through a ROS-mediated mitochondrial pathway. Free Radical Biology & Medicine 45: 60–72. 10.1016/j.freeradbiomed.2008.03.013

Cui, F.X., Xue, C.H., Li, Z., Zhang, Y.Q., Dong, P., Fu, X.Y. and Gao, X., 2007. Characterization and subunit composition of collagen from the body wall of sea cucumber Stichopus japonicus. Food Chemistry 100: 1120–1125. 10.1016/j.foodchem.2005.11.019

Dar, P.A., Mir, S.A., Bhat, J.A., Hamid, A., Singh, L.R., Malik, F. and Dar, T.A., 2019. An anti-cancerous protein fraction from Withania somnifera induces ROS-dependent mitochondria-mediated apoptosis in human MDA-MB-231 breast cancer cells. International Journal of Biological Macromolecules 135: 77–87. 10.1016/j.ijbiomac.2019.05.120

Dodgson, K. and Price, R., 1962. A note on the determination of the ester sulphate content of sulphated polysaccharides. Biochemical Journal 84: 106–110. 10.1042/bj0840106

Doynikova, A.N. and Vekshin, N.L., 2019. Fluorescent determination of micro-quantities of RNA using Hoechst 33258 and binase. Analytical Biochemistry 576: 5–8. 10.1016/j.ab.2019.04.002

Filisetticozzi, T.M.C.C. and Carpita, N.C., 1991. Measurement of uronic acids without interference from neutral sugars. Analytical Biochemistry 197: 157–162. 10.1016/0003-2697(91)90372-Z

Hu, X.Q., Li, Z.J., Xue, Y., Xu, J., Xue, C.H., Wang, J.F. and Wang, Y.M., 2012. Dietary saponins of sea cucumber ameliorate obesity, hepatic steatosis, and glucose intolerance in high-fat diet–fed mice. Journal of Medicinal Food 15: 909–916. 10.1089/jmf.2011.2042

Huang, W., Deng, H., Jin, S.Y., Yang, W.B., Wang, H.L., Meng, C.Q., Wang, H. and Yang, S.H., 2019. A polysaccharide from dried aerial parts of Agrimonia pilosa: structural characterization and its potential therapeutic activity for steroid-induced necrosis of the femoral head (SANFH). Carbohydrate Polymers 214: 71–79. 10.1016/j.carbpol.2019.03.004

Huggins, M., 1942. The viscosity of dilute solutions of long-chain molecules. IV. Dependence on concentration. Journal of the American Chemical Society 64: 2716–2718. 10.1021/ja01263a056

Janakiram, N., Mohammed, A. and Rao, C., 2015. Sea cucumbers metabolites as potent anti-cancer agents. Marine Drugs 13: 2909–2923. 10.3390/md13052909

Li, Q., Che, H.-X., Wang, C.-C., Zhang, L.-Y., Ding, L., Xue, C.-H., Zhang, T.-T. and Wang, Y.-M., 2019. Cerebrosides from sea cucumber improved Aβ1–42-induced cognitive deficiency in a rat model of Alzheimer’s disease. Molecular Nutrition & Food Research 63: 1800707. 10.1002/mnfr.201800707

Lin, F. and Pomeranz, Y., 1968. Effect of borate on colorimetric determinations of carbohydrates by the phenol-sulfuric acid method. Analytical Biochemistry 24: 128–131. 10.1016/0003-2697(68)90067-5

Lin, L.Z., Kun, Y., Lin, Z., Ming, Z.M., Zheng, S.W., Yuan, Z.Q. and Jun, L.S., 2018. Anti-aging effect of sea cucumber (Cucumaria frondosa) hydrolysate on fruit flies and d-galactose-induced aging mice. Journal of Functional Foods 47: 11–18. 10.1016/j.jff.2018.05.033

Liu, X., Liu, J., Zhang, J., Wang, T., Wang, G., Jing, Y. and Zhao, Y., 2016a. Purification and antitumor activity in vitro of polysaccharides from Apostichopus japonicus spawn. Food Science 37: 105–110.

Liu, X.X., Hao, J.J., Shan, X.D., Zhang, X., Zhao, X.L., Li, Q.Y., Wang, X.J., Cai, C., Li, G.Y. and Yu, G.L., 2016b. Antithrombotic activities of fucosylated chondroitin sulfates and their depolymerized fragments from two sea cucumbers. Carbohydrate Polymers 152: 343–350. 10.1016/j.carbpol.2016.06.106

Liu, F., Sun, X., Zhu, W., Guo, Y., Liu, H.E., Yang, Z., Wang, Y., Wen, Y. and Wang, L., 2018. Establishment and determination of monosaccharide in sea cucumber. Progress in Fishery Sciences 39(2): 177–182. 10.19663/j.issn2095-9869.20170111001

Liu, X., Sun, Z.L., Zhang, M.S., Meng, X.M., Xia, X.K., Yuan, W.P., Xue, F. and Liu, C.H., 2012. Antioxidant and antihyperlipidemic activities of polysaccharides from sea cucumber Apostichopus japonicus. Carbohydrate Polymers 90: 1664–1670. 10.1016/j.carbpol.2012.07.047

Lu, Y. and Wang, B.L., 2009. The research progress of antitumorous effectiveness of Stichopus japonicus acid mucopolysaccharide in North of China. The American Journal of the Medical Sciences 337: 195–198. 10.1097/MAJ.0b013e318182ee45

Mathur, A., Hong, Y., Kemp, B.K., Barrientos, A.A. and Erusalimsky, J.D., 2000. Evaluation of fluorescent dyes for the detection of mitochondrial membrane potential changes in cultured cardiomyocytes. Cardiovascular Research 46: 126–138. 10.1016/S0008-6363(00)00002-X

Myron, P., Siddiquee, S. and Azad, S.A., 2017. Partial structural studies of fucosylated chondroitin sulfate (FuCS) using attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and chemometrics. Vibrational Spectroscopy 89: 26–36. 10.1016/j.vibspec.2016.12.008

Pérez-Vega, J.A., Olivera-Castillo, L., Gómez-Ruiz, J.Á. and Hernández-Ledesma, B., 2013. Release of multifunctional peptides by gastrointestinal digestion of sea cucumber (Isostichopus badionotus). Journal of Functional Foods 5: 869–877. 10.1016/j.jff.2013.01.036

Pollard, J., Rajabi-Siahboomi, A., Badhan, R.K.S., Mohammed, A.R. and Perrie, Y., 2019. High-throughput screening of excipients with a biological effect: a kinetic study on the effects of surfactants on efflux-mediated transport. Journal of Pharmacy and Pharmacology 71: 889–897. 10.1111/jphp.13072

Rajpurohit, R., Mansfield, K., Ohyama, K., Ewert, D. and Shapiro, I., 1999. Chondrocyte death is linked to development of a mitochondrial membrane permeability transition in the growth plate. Journal of Cellular Physiology 179: 287–296. 10.1002/(SICI)1097-4652(199906)179:3<287::AID-JCP6>3.0.CO;2-T

Shin, G.-C., Kim, C., Lee, J.-M., Cho, W.-S., Lee, S.-G., Jeong, M., Cho, J. and Lee, K., 2009. Apigenin-induced apoptosis is mediated by reactive oxygen species and activation of ERK1/2 in rheumatoid fibroblast-like synoviocytes. Chemico-Biological Interactions 182: 29–36. 10.1016/j.cbi.2009.07.016

Siegel, R.L., Miller, K.D. and Jemal, A., 2016. Cancer statistics, 2016. CA: A Cancer Journal for Clinicians 66: 7–30. 10.3322/caac.21332

Sinha, K., Das, J., Pal, P.B. and Sil, P.C., 2013. Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Archives of Toxicology 87: 1157–1180. 10.1007/s00204-013-1034-4

Song, S., Wu, S.F., Ai, C.Q., Xu, X., Zhu, Z.J., Cao, C.Y., Yang, J.F. and Wen, C.R., 2018. Compositional analysis of sulfated polysaccharides from sea cucumber (Stichopus japonicus) released by autolysis reaction. International Journal of Biological Macromolecules 114: 420–425. 10.1016/j.ijbiomac.2018.03.137

Sun, Y.J., Gong, G.P., Guo, Y.M., Wang, Z.F., Song, S., Zhu, B.W., Zhao, L.L. and Jiang, J.J., 2018. Purification, structural features and immunostimulatory activity of novel polysaccharides from Caulerpa lentillifera. International Journal of Biological Macromolecules 108: 314–323. 10.1016/j.ijbiomac.2017.12.016

Szeleszczuk, Ł., Pisklak, D.M., Zielińska-Pisklak, M. and Jurczak, E., 2019. A new polymorph of 17-β-estradiol and the application of different analytical techniques (ssNMR, PXRD, DSC, and FTIR) for its study. Journal of Molecular Structure 1183: 274–280. 10.1016/j.molstruc.2019.01.102

Tang, Y.J., Zhao, H., Yao, J.H., Zhu, Z.H., Sun, D.H. and Zhang, M., 2019. A doxorubicin and vincristine drug release system based on magnetic PLGA microspheres prepared by coaxial electrospray. Journal of Materials Science 54: 9689–9706. 10.1007/s10853-019-03575-9

Thinh, P.D., Ly, B.M., Usoltseva, R.V., Shevchenko, N.M., Rasin, A.B., Anastyuk, S.D., Malyarenko, O.S., Zvyagintseva, T.N., San, P.T. and Ermakova, S.P., 2018. A novel sulfated fucan from Vietnamese sea cucumber Stichopus variegatus: isolation, structure and anticancer activity in vitro. International Journal of Biological Macromolecules 117: 1101–1109. 10.1016/j.ijbiomac.2018.06.017

Ustyuzhanina, N.E., Bilan, M.I., Dmitrenok, A.S., Borodina, E.Y., Stonik, V.A., Nifantiev, N.E. and Usov, A.I., 2017. A highly regular fucosylated chondroitin sulfate from the sea cucumber Massinium magnum: structure and effects on coagulation. Carbohydrate Polymers 167: 20–26. 10.1016/j.carbpol.2017.02.101

Vaikundamoorthy, R., Krishnamoorthy, V., Vilwanathan, R. and Rajendran, R., 2018. Structural characterization and anticancer activity (MCF7 and MDA-MB-231) of polysaccharides fractionated from brown seaweed Sargassum wightii. International Journal of Biological Macromolecules 111: 1229–1237. 10.1016/j.ijbiomac.2018.01.125

Wu, F.J., Xue, Y., Tang, Q.J., Xu, J., Du, L., Xue, C.H., Takahashi, K. and Wang, Y.M., 2013. The protective effects of cerebrosides from sea cucumber and starfish on the oxidative damage in PC12 cells. Journal of Oleo Science 62: 717–727. 10.5650/jos.62.717

Xiong, Q.P., Song, Z.Y., Hu, W.H., Liang, J., Jing, Y., He, L., Huang, S., Wang, X.L., Hou, S.Z., Xu, T.T., Chen, J., Zhang, D.Y., Shi, Y.Y., Li, H.L. and Li, S.J., 2018. Methods of extraction, separation, purification, structural characterization for polysaccharides from aquatic animals and their major pharmacological activities. Critical Reviews in Food Science and Nutrition 60: 1–16. 10.1080/10408398.2018.1512472

Xu, D.X., Zhang, J.J., Cao, Y.P., Wang, J. and Xiao, J.S., 2016. Influence of microcrystalline cellulose on the microrheological property and freeze-thaw stability of soybean protein hydrolysate stabilized curcumin emulsion. LWT–Food Science and Technology 66: 590–597. 10.1016/j.lwt.2015.11.002

Yang, D., Lin, F., Huang, Y., Ye, J. and Xiao, M., 2019. Separation, purification, structural analysis and immune-enhancing activity of sulfated polysaccharide isolated from sea cucumber viscera. International Journal of Biological Macromolecules 155:1003–1018. 10.1016/j.ijbiomac.2019.11.064

Yang, W.J., Cai, Y., Yin, R.H., Lin, L.H., Li, Z.K., Wu, M.Y. and Zhao, J.H., 2018. Structural analysis and anticoagulant activities of two sulfated polysaccharides from the sea cucumber Holothuria coluber. International Journal of Biological Macromolecules 115: 1055–1062. 10.1016/j.ijbiomac.2018.04.175

Ye, L., Xu, L. and Li, J., 2012. Preparation and anticoagulant activity of a fucosylated polysaccharide sulfate from a sea cucumber Acaudina molpadioidea. Carbohydrate Polymers 87: 2052–2057. 10.1016/j.carbpol.2011.10.014

Yu, L., Xue, C.H., Chang, Y.G., Hu, Y.F., Xu, X.Q., Ge, L. and Liu, G.C., 2015. Structure and rheological characteristics of fucoidan from sea cucumber Apostichopus japonicus. Food Chemistry 180: 71–76. 10.1016/j.foodchem.2015.02.034

Yun, L.Y., Wu, T., Liu, R., Li, K. and Zhang, M., 2018. Structural variation and microrheological properties of a homogeneous polysaccharide from wheat germ. Journal of Agricultural and Food Chemistry 66: 2977–2987. 10.1021/acs.jafc.7b04730

Zhang, W., Lu, Y., Xu, B., Wu, J., Zhang, L., Gao, M., Zheng, S., Wang, A., Zhang, C., Chen, L. and Lei, N., 2009. Acidic mucopolysaccharide from Holothuria leucospilota has antitumor effect by inhibiting angiogenesis and tumor cell invasion in vivo and in vitro. Cancer Biology & Therapy 8: 1489–1499. 10.4161/cbt.8.15.8948

Zhang, T.T., Xu, J., Wang, Y.M. and Xue, C.H., 2019. Health benefits of dietary marine DHA/EPA-enriched glycerophospholipids. Progress in Lipid Research 75: 100997. 10.1016/j.plipres.2019.100997

Zhang, B., Xue, C., Hu, X., Xu, J., Li, Z., Wang, J., Yanagita, T., Xue, Y. and Wang, Y., 2012. Dietary sea cucumber cerebroside alleviates orotic acid-induced excess hepatic adipopexis in rats. Lipids in Health and Disease 11: 48. 10.1186/1476-511X-11-48

Zhang, T.T., Yang, L. and Jiang, J.G., 2015a. Effects of thonningianin A in natural foods on apoptosis and cell cycle arrest of HepG-2 human hepatocellular carcinoma cells. Food & Function 6: 2588–2597. 10.1039/C5FO00388A

Zhang, T.T., Yang, L. and Jiang, J.G., 2015b. Tormentic acid in foods exerts anti-proliferation efficacy through inducing apoptosis and cell cycle arrest. Journal of Functional Foods 19: 575–583. 10.1016/j.jff.2015.09.061

Zhao, Y.H., Li, B.F., Liu, Z.Y., Dong, S.Y., Zhao, X. and Zeng, M.Y., 2007. Antihypertensive effect and purification of an ACE inhibitory peptide from sea cucumber gelatin hydrolysate. Process Biochemistry 42: 1586–1591. 10.1016/j.procbio.2007.08.011

Zhao, Y.C., Xue, C.H., Zhang, T.T. and Wang, Y.M., 2018. Saponins from sea cucumber and their biological activities. Journal of Agricultural and Food Chemistry 66: 7222–7237. 10.1021/acs.jafc.8b01770

Zhou, X.Q., Wang, C.H. and Jiang, A.L., 2012. Antioxiant peptides isolated from sea cucumber Stichopus japonicus. European Food Research and Technology 234: 441–447. 10.1007/s00217-011-1610-x

Zhu, X., Wang, K., Zhang, K., Zhu, L. and Zhou, F., 2014. Ziyuglycoside II induces cell cycle arrest and apoptosis through activation of ROS/JNK pathway in human breast cancer cells. Toxicology Letters 227: 65–73. 10.1016/j.toxlet.2014.03.015