Food industrial importance of sea cucumber
Sea cucumber fisheries have quickly expanded cosmopolitan in the get and value over the past two to three decades ( Anderson et aluminum. 2011 ). It has a significant commercial measure because it has high valuable alimentary content of vitamins and minerals, and a number of classifiable biologically and pharmacologically bioactive compounds. Sea cucumber provides a generator of nutrition to possibly more than one billion asian consumers and around 10,000 thyroxine of dried ocean cucumber is traded internationally per annum ( Purcell et alabama. 2016 ). They are normally processed into a frigid, cooked-dried, cooked-salted, and cooked-salted-dried products ( Aydin et alabama. 2011 ). however, about sea cucumber exported in dried products form and a small measure of bracing and freeze products shape. closely 90 % of this trade takes seat in the Asian Far East where China Hong Kong SAR and Singapore dominate the clientele and China PR remains the chief consume nation ( Ferdouse 2004 ). The proximate composition of sea cucumbers differs depending upon the seasonal variations, geographic placement, and feeding regimes. postpone 1 shows that moisture of wet sea cucumber and protein, ash, and fat contents of dry sea cucumber vary from 90.8 to 93.4, 29.9 to 48.1, 18.4 to 47.8, and 1.3 to 7.0 %, respectively. In addition, proximate composition of wet matter showed that moisture, protein, ash, fat, and carbohydrates contents of dried ocean cucumber deviate from 80.2 to 93, 1.1 to 5.4, 2.4 to 6.9, 0.1 to 2.2 and 0.2 to 0.6 %, respectively.
Table 1 Proximate composition of sea cucumber Stichopus japonicus in the various papers Full size table
Bioactive components and pharmaceutical industrial importance of sea cucumber
many marines derived naturally compounds are of great pastime for a electric potential new ingredient for versatile industrial applications. Among the marine invertebrate, sea cucumbers are one of the electric potential high food and medicative in Asia and reported with relatively high economic and food respect. They have been recognized in folk music medicate systems of asian countries and as having an impressive range of medicative health functions for nourishing the body, detoxifying the kidneys, moistening dryness of the intestines, treatment of stomach ulcers, asthma, antihypertension, rheumatoid arthritis and wound healing ( Alves RRN, and Rosa IL 2012 ). The therapeutic properties and medicative benefits of ocean cucumbers can be linked to the presence of a wide array of bioactive ( Bordbar et aluminum. 2011 ). nutritionally, a count of unique biological and pharmacological activities and have respective bioactive components such as peptides, fatty acids, glycosaminoglycan ( chondroitin/fucan sulfates ), nortriterpene/triterpene glycosides, other extracts, and hydrolysates ( table 2 ). A number of authoritative bioactive compounds identified in S. japonicus are listed in table 3 .Table 2 Various biological activities of sea cucumber Stichopus japonicus component Full size tableTable 3 Bioactive compounds of Stichopus japonicus
Full size table
Biological activities
α-Glucosidase inhibition
Diabetes is one of the most good, chronic disease and causes enormous human miserable in the shape of blindness, kidney failure, amputations, and increased risk of coronary artery disease and solidus ( Taylor 1999 ). There are two common forms of diabetes : character 1 diabetes, which is insulin subject, and type 2, which is non-insulin dependent. Type 2 diabetes is the most common form, accounting for 90–95 % of all cases of diabetes ( Moller 2001 ). In type 2 diabetes, control of glucose horizontal surface is a major focus in disease management. α-Glucosidase is a samara carbohydrate-hydrolyzing enzymes involved in carbohydrate dislocation and assimilation in the digestive tract ( Heo et aluminum. 2009 ). consequently, α-glucosidase inhibitor such as acarbose, miglitol, and voglibose are wide used in the treatment of patients with type 2 diabetes to prevent the dislocation and assimilation of carbohydrates after food uptake. however, α-glucosidase inhibitor has gastrointestinal side effects such as flatulence, diarrhea and abdominal cramps ( Chiasson et alabama. 2002 ). Nguyen et aluminum. ( 2011 ) determined that two unsaturated fatty acids from n-hexane divide of ocean cucumber body wall inhibit α-glucosidase activities. The two isolated unsaturated fatso acids were structurally identified using NMR and EI-MS. The two unsaturated fatso acids are identified as 7 ( Z ) -octadecenoic acidic and 7 ( Z ) ,10 ( Z ) -octadecadienoic acid. These unsaturated fatty acids showed a dose dependent inhibition of α-glucosidase through mix inhibition. In especial, 7 ( Z ) ,10 ( Z ) -octadecadienoic acid was found to be a more effective α-glucosidase inhibitor than 7 ( Z ) -octadecenoic acerb. therefore, these two unsaturated fatso acids can potentially be developed as a novel natural pharmaceutical agent .
Anti-cancer
Cancer is a disease in which continuous clonal expansion of bodily cells causes death by invading, subverting, and eroding the normal tissues ( Evan and Vousden 2001 ). Abnormal cell cycle rule can result in cancerous growth and developmental abnormalities by uncontrolled increase and proliferation of cells ( Maddika et alabama. 2007 ). The authoritative operate of cancer is the prohibition of abnormal cell growth and cell proliferation by anti-cancer agents. The some sea cucumber S. japonicus has been reported a electric potential source of anti-cancer drugs. Park et alabama. ( 2011 ) extracted S. japonicus with unlike solvents and evaluated the anti-cancer activity in HL-60 and HT-29 cells. Among the solution extracts, EtOAc fractions showed higher cell increase inhibition than early solvent fractions. In the protein expression, EtOAc fractions decreased the archetypal anti-apoptotic protein ( Bcl-2 ) and increased the cleaved caspase-3 and poly ( ADP-ribose ) polymerase ( PARP ). In another report, Lu et alabama. ( 2010 ) extracted acerb mucopolysaccharide from S. japonicus ( SJAMP ) and examined the apoptosis impression against human hepatocellular carcinoma cell line HepG2. The results showed that SJAMP inhibited the HepG2 cell proliferation and induce apoptosis by down-regulation of Bcl-2 and up-regulation of nm23-H1 gene formulation in a time and dose dependent manner. In addition, Kim et alabama. ( 2017 ) extracted through ultrasonification extraction process at 50 °C and 95 kilohertz for 2 hydrogen ( UE ) and investigated the anti-skin cancer activities compared with those from conventional extraction action in human skin malignant melanocytomas ( SK-Mel-2 ) cells. The results showed that UE extracts inhibited the SK-Mel-2 cell proliferation and metastasis through reduction the expression of skin tumor-promoting genes such as Bcl-2, STAT3, and MMP-9. These reports suggest the use of the sea cucumber S. japonicus as a natural source of the potential anticancer drug .
Anti-coagulation
Coagulation besides known as clot is a styptic system that prevents of rake loss from the damaged blood vessels and keeps lineage in a fluid department of state through the rapid formation of a clot ( Mackman et aluminum. 2007 ). The curdling process is initiated as a consequence of the conversion of prothrombin to thrombin in the presence of calcium by releasing tissue agent ( besides known as thromboplastin ) from damaged vessels ( Versteeg et alabama. 2013 ). Thrombin is a key enzyme in the curdling work and is produced by a tightly regulated series of reactions through the geological formation of the factor Xa/Va complex ( Gailani and Renné 2007 ). The prothrombin time ( PT ) and activated fond thromboplastin time ( APTT ) are used to the screening curdling assays in clinical exercise for determining extrinsic or intrinsic curdling pathways ( Gailani and Renné 2007 ). normally, anticoagulants such as heparin are used for the prevention of blood clotting during vascular surgery. however, heparin can cause a phone number of english effects such as osteoporosis, thrombocytopenia, increased functional action of platelets and hemorrhagic complications ( Mestechkina and Shcherbukhin 2010 ). therefore, there is a need to replace heparin with new safe anticoagulants. Yang et aluminum. ( 2015a ) isolated a novel depolymerized fucosylated chondroitin sulfate from S. japonicus ( DAHG ) by Cu2+ catalytic free-radical depolymerization and demonstrated its anticoagulant activities compared with low molecular weight unit heparin ( LMWH ; average molecular weight 3500 Da ). The DAHG was fractionated into three different low molecular weight fractions such as DAHG-1 ( 41,149 Da ), DAHG-2 ( 24,755 Da ) and DAHG-3 ( 8871 Da ). During APTT assay, DAHG-2 and LMWH were shown to have about the lapp anticoagulant activity. In summation, DAHG-2 had significantly less bleeding risk compared with LMWH at an equivalent concentration. therefore, DAHG-2 could be used as a novel natural anticoagulant with fewer side effects. In another study, a novel glucosidic traffic pattern of fucose ( AHG ; molecular weight 98,070 Da ) was found in the glycosaminoglycan and AHG structure was elucidated by 1/2 dimension NMR ( Yang et aluminum. 2015b ). The anticoagulant activities were performed by APTT and thrombin time ( TT ) assays. For APTT bodily process, the concentration of AHG less than 170 μg/ml showed to have about the same anticoagulant activity as that by unfractionated heparin. however, the higher AHG concentration of 170 μg/ml showed slightly lower anticoagulant bodily process compared to that by the unfractionated heparin. In the sheath of TT action, AHG has slightly higher anticoagulant activity than heparin, suggesting that AHG isolated from A. japonicus could be used a potential anticoagulant drug .
Anti-fungal activity
In the past two decades, the incidence of invasive fungal infection has continued to increases. These fungal infections are major causes of morbidity and mortality in neutropenic patients which includes individuals undergoing organ, blood, and marrow transplant, and those receiving intensive chemotherapy or other immunosuppressive treatments ( Patterson 2005 ). Among the opportunist mycoses, Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus are the most common invasive mycoses in these patients ( Pfaller et alabama. 2006 ). The calculate annual incidence of encroaching mycoses is 72–290 infections per million population for Candida, 30–66 infections per million for C. neoformans, and 12–34 infections per million population for Aspergillus species ( Pfaller and Diekema 2010 ). Although antifungal drugs such as deoxycholate amphotericin B, triazoles, itraconazole, and voriconazole are used for the treatment of encroaching fungal infections, these drugs cause english effects such as nephrotoxicity, hepatotoxicity, and hazardous drug interactions ( Maertens et aluminum. 2004 ). consequently, exploitation of newly fungicidal agents is needed for the safe and effective discussion of incursive fungal infections. recently, Wang et alabama. ( 2012 ) isolated and elucidated nortriterpene glycoside and triterpene glycosides with fungicidal properties from the ethanolic extracts of ocean cucumber. The chemical structure of eight compounds such as 26-nor-25-oxo-holotoxin A1, ( C65H102O32Na, 1417.6252 ) holotoxin D ( C66H104O32Na, 1431.6408 ), holotoxin E ( C65H102O31Na, 1401.6313 ), holotoxin F ( C59H96O25Na, 1227.6138 ) and holotoxin G ( C58H94O25Na, 1213.5982 ) with three known holotoxin A1 and B, and cladoloside B were identified by HPLC, NMR, and MS. According to their results, although some compounds ( 1, 4, and 5 ) exhibited selective potent fungicidal activities against six fungal strains such as Candida albicans, C. tropicalis, Cryptococcus neoformans, Trichophyton rubrum, Microsporum gypseum, and Aspergillus fumigatus, the 18 ( 20 ) lactone group and the Δ25 terminal double chemical bond may increase the activity .
Anti-hyperlipidemic activity
Hyperlipidemia is one of the risk factors contributing to the growth and progress of cardiovascular diseases including coronary thrombosis heart disease ( Machado et alabama. 2008 ). Hyperlipidemia is characterized by the increased total cholesterol and triglycerides, broken density lipoprotein ( LDL ), identical low concentration lipoprotein ( VLDL ), and decreased high density lipoprotein ( HDL ) ( Huang et alabama. 2006 ). The LDL is the major transporter of cholesterol to peripheral cells, while HDL returns the excess weave cholesterol to the liver by reversion cholesterol transmit ( Ikonen 2008 ). Although lipid-lowering drugs such as HMG-CoA reductase inhibitors, fibrates and bile acid-sequestering resins have been used for the treatment of lipemia, these drugs have side effects such as liver steatosis or hypertriglyceridemia ( Li et alabama. 2015 ). consequently, growth of a safe and effective treatment for lipemia is however a challenge to the current aesculapian therapy. The polysaccharides from A. japonicus ( AJP ) were extracted by the protease hydrolysis method acting and tested for anti-hyperlipidemic bodily process in vivo experiment by Lui et aluminum. ( 2012b ). The AJP extract was chiefly composed of glucosamine, galactosamine, glucuronic acid, mannose, glucose, galactose, and fucose, with a molecular weight of about 36.2 kDa. The anti-hyperlipidemic activity of AJP at 200, 400, and 800 mg/kg was investigated by serum total cholesterol ( TC ), triglyceride ( TG ), LDL-cholesterol ( LDL-C ) and HDL-cholesterol ( HDL-C ) using an enzymatic colorimetric method acting in hyperlipidemic Wistar rats for 28 days. The rats fed with AJP at 400 mg/kg showed that TC, TG, and LDL-C concentrations decreased significantly by 17.23, 20.78, and 31.18 %, respectively, and HDL-C increased by 27.27 % as compared to the hyperlipidemic group. Although, the mechanism of AJP on anti-hyperlipidemic activity needs to be silent clarified, AJP could be a potential curative target for lipemia .
Anti-inflammation
The incendiary response is one of the most authoritative defense mechanism for security during microbial infection and tissue injury. During the incendiary process, macrophages are activated by endogenous and exogenous factors, which release assorted proinflammatory factors such as azotic oxide ( NO ) from inducible NO synthase ( iNOS ) and prostaglandin E2 ( PGE2 ) from cyclooxygenase-2 ( COX-2 ), and cytokines such as interleukins, IL-1β, IL-6, and tumor necrosis factor ( TNF-α ) ( Xu et aluminum. 2014 ). normally, inflammatory and healing processes are interrelated. The factors creditworthy for incendiary reply are besides involved in the heal process. The excessive host incendiary reaction by the overproduction of incendiary mediators can lead to versatile diseases such as asthma, arthritic arthritis, psoriatic arthritis, systemic lupus erythematosus, Crohn ’ randomness disease, multiple sclerosis, and systemic vasculitis ( Tung et alabama. 2008 ). consequently, anti-inflammatory activity is an important remedy scheme for diverse inflammatory diseases. Himaya et alabama. ( 2010 ) extracted the ethyl acetate rayon fraction from S. japonicus ( SCEA-F ) by solvent divide and tested for the anti-inflammatory action through NO and PGE2 production assay, iNOS and COX-2 protein and gene formula level, proinflammatory cytokines saying level ( IL-1β and TNF-α ) and mitogen-activated protein kinases ( MAPK, ERK, and p38 MAPK ) on lipopolysaccharide ( LPS ) -induced murine macrophages. The results show that SCEA-F has a higher incendiary activeness as compared with another solution fraction ( hexane, chloroform, and butyl alcohol ) in a dose-dependent manner. In accession, SCEA-F inhibited the ERK and p38 MAPK phosphorylation in LPS-induced macrophage cells. similarly, the anti-inflammatory activity of solution fraction from S. japonicus was investigated by Park et aluminum. ( 2011 ). The result showed that ethyl acetate rayon ( EtOAc ) fractions exhibited strong anti-inflammatory action as compared with another solvent fraction. therefore, ethyl acetate fractions from S. japonicus could be used as an effective anti-inflammation agent .
Anti-melanogenesis
Melanogenesis is the process of melanin synthesis by a shower of enzymatic reactions that convert tyrosine to melanin pigments such as eumelanin, pheomelanin, neuromelanin, and assorted melanin pigment ( Slominski et aluminum. 2004 ). Melanin is a assortment of pigment biopolymers synthesized in specialize cells known as melanocytes by melanin deduction related enzymes such as tyrosinase, TRP-1 and TRP-2 ( Ito 2003 ). It provides the color of the animal peel, hair’s-breadth, and eyes and protects against the harmful effect of UV radiotherapy. however, the overproduction of melanin causes serious aesthetic problems such as freckle, liver spots and chloasma ( Oh et alabama. 2015 ). In the melanin synthesis related enzymes, tyrosinase is the rate-limiting enzyme and plays a critical regulative character in the first pace of melanogenesis ( Qiao et alabama. 2012 ). therefore, inhibition of tyrosinase is one of the important treatment methods of aesthetic problems. Although, tyrosinase inhibitors including hydroquinone, kojic acid, azelaic acid, electron-rich phenols and arbutin have been used for the treatment of abnormal pigmentation through prohibition of converting tyrosine to l-dihydroxyphenylalanine ( L-DOPA ), these tyrosinase inhibitors have many side effects such as skin irritation, cytotoxic to melanocytes, carcinogenicity, low formulation constancy and poor people hide penetration ( Chen et aluminum. 2015 ).
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Yoon et alabama. ( 2010 ) evaluated the anti-melanogenesis activity of the ethanolic extracts and solvent-partitioned fractions ( n -hexane, CHCl3, EtOAc, BuOH, and body of water ) from S. japonicus. The results indicate that EtOAc causes the highest reduction of melanin contented and the formulation of melanogenesis-related proteins ( tyrosinase, TRP-1, TRP-2, and MITF ) in B16 cells. furthermore, it has been shown that S. japonicus excerpt did not cause any hard adverse reactions on homo peel by conducting mend tests for 2 to 3 days. In another learn, Husni et alabama. ( 2011 ) isolated and elucidated the two tyrosinase inhibitors from the ethyl alcohol and water extracts of S. japonicus body rampart by HPLC and NMR. The results show that ethyl alcohol extracts exhibited higher tyrosinase inhibitory activity than the water extracts. Compound 1 ( adenosine ) had molecular weight of 267.241 g/mol ( C10H13N5O4 ) and compound 2 ( ethyl-α-D-glucopyranoside ) had molecular system of weights of 208.209 g/mol ( C8H16O6 ). Regarding the tyrosinase inhibitory effects, adenosine and ethyl-α-D-glucopyranoside has IC50 value of 0.191 and 0.126 mg/ml, respectively. In addition, Oh et alabama. ( 2017 ) investigated the effects of S. japonicus extracts on melanogenesis in B16F10 and Melan-A cells. The results indicated that ethyl alcohol extracts cause the reduction expression flush of tyrosinase, TRP-1, TRP-2, and MITF by phosphorylation of ERK. Therefore, ocean cucumber may be a good source for natural tyrosinase inhibitors .
Anti-osteoclastogenesis
Bone is a dynamic tissue playing support functions and physical protective covering of organs and is constantly remodeled throughout liveliness. The cram formation and resorption remodel process are tightly coupled, and bone homeostasis is maintained by the poise between bone formation by osteoblast and cram resorption by osteoclast ( Pederson et aluminum. 2008 ). Exceed bone resorption can lead to metabolic bone diseases such as osteoporosis ( Cuong et aluminum. 2010 ). osteoporosis is characterized by decrease in bone mineral density due to excessive bone resorption by osteoclasts. Although respective anti-resorptive drugs such as alendronate, risedronate, ibandronate, zoledronic acerb, raloxifene and strontium ranelate are used for osteoporosis, their use is limited by a issue of side effects, such as oesophageal annoyance, acute-phase reaction, hypocalcemia, electric potential nephritic toxic effects and thromboembolic disease ( Rachner et aluminum. 2011 ). consequently, new safe and effective antiresorptive drugs are needed. Kariya et alabama. ( 2004 ) isolated the two types of fucan sulfate from chloroform/methanol extract of S. japonicus body wall. They used NMR spectroscopy to elucidate the structure of fucan sulfite A and B. Type A contains 3.41 mmol fucose/g and 2.35 mmol sulfate/g and had a molecular mass of 9 kDa. Another character B contained 3.90 mmol fucose/g and 3.07 mmol sulfate/g and had a molecular batch of 32 kDa. In the in vitro assay for osteoclast formation, types A and B fucan sulfate inhibited osteoclast-like cell formation by 99.8 and 96.3 %, respectively. These results suggest that fucan sulfates A and B have great likely to be used as a source for natural anti-osteoclastogenesis reagent .
Anti-oxidation
reactive oxygen species ( ROS ) such as superoxide anion radical ( O2 − ), hydrogen hydrogen peroxide ( H2O2 ) and hydroxyl radicals ( · OH ) are continuously generated in normal oxygen consuming metabolic process. They operate as intracellular signaling molecules and protect from microbial infection ( Fang 2004 ). normally, the ROS are controlled by the barren free radical scavenge enzymes that convert superoxide anions to hydrogen hydrogen peroxide ( Mn2+-dependent superoxide dismutase [ MnSOD ] and copper/zinc [ Cu/Zn ] SOD ) and hydrogen peroxide to water ( glutathione peroxidase [ GPx ] and catalase [ CAT ] ) and glutathione reductase ( GR ) ( Wei and Lee 2002 ). however, overproduction of ROS by the environmental divisor such as ionize, UV radiation or numerous compounds can cause oxidative wrong to biomacromolecules such as lipids, proteins, and nucleic acids by affecting the cells defense capacity ( Cabiscol et aluminum. 2000 ). oxidative stress by overproduction of ROS can cause many age-dependent diseases such as atherosclerosis, osteoarthritis, neurodegenerative disorders ( including Parkinson ’ mho disease, Alzheimer ’ second disease, amyotrophic lateral sclerosis, and Huntington ’ s disease ) and cancer ( Bickers and Athar 2006 ; Lin and Beal 2006 ). therefore, anti-oxidant compounds are the most authoritative factors for renovation and protection of the homo body from oxidative damage. The antioxidant activities of four types of ocean cucumber extracts have been investigated by Husni et aluminum. ( 2009 ). The sea cucumber extracts were prepared by performing heat reflux and supercharge solvent extractions with two solvents such as water and 70 % ethyl alcohol. The antioxidant activities were evaluated by 2, 2-diphenyl-1-picrylhydrazyl ( DPPH ) and 2, 2-azinobis ( 3-ethylbenzothiazoline-6-sulfonic acidic ) ( ABTS ) radical salvage activities. They suggested that the water or 70 % ethyl alcohol distill by bare heat reflux extraction could have contributed to the antioxidant benefits. In another investigation, low-molecular-weight gelatin hydrolysate ( LMW-GH, 700–1700 Da ) was extracted from the body wall of S. japonicus by hydrolyzation with flavourzyme ( Wang et alabama. 2010 ). The LMW-GH exhibited high superoxide and hydroxyl group scavenge activity in a dose-dependent manner. The IC50 value of superoxide and hydroxyl radicals were 442 and 285 μg/ml, respectively. Zheng et aluminum. ( 2012 ) identified an antioxidative oligopeptide from autolysis hydrolysates of S. japonicus guts. Two tetrapeptides Val-Thr-Pro-Tyr ( 497 Da ), Val-Leu-Leu-Tyr ( 507 Da ) and a hexapeptide Val-Gly-Thr-Val-Glu-Met ( 635 Da ) were elucidated by ESI-MS/MS and exhibited antioxidant activities by the protective covering of hydroxyl radical-induced DNA damage. These oligopeptides exhibited protective barrier against hydroxyl radical-induced deoxyribonucleic acid damage at a assiduity of 2 mg/ml. Zhou et alabama. ( 2012 ) besides studied the antioxidant action of a fresh peptide from S. japonicus by hydrolyzation with trypsin. The peptide was sequenced as GPEPTGPTGAPQWLR and IC50 values of hydroxyl and superoxide radical scavenge bodily process were 138.9 and 353.9 μM, respectively. Zhu et aluminum. ( 2012 ) extracted a high-purity pepsin-solubilized collagen ( PSC ) from S. japonicus body wall and studied its hydroxyl and DPPH radical scavenge activities. The results showed that PSC has importantly higher hydroxyl and DPPH radical scavenge activities than that of vitamin C. In accession, AJP was besides investigated for antioxidant activities such as DPPH, hydroxyl and superoxide radicals, and reducing power by Lui et alabama. ( 2012b ). therefore, S. japonicus has great electric potential as a reference for natural antioxidant .
Immunomodulatory effect
The congenital immune system is composed of many interdependent cell types and mediators, and is one of the most important natural systems for protection against a large count of harmful bacteria, viruses, parasites and fungi in human health and against autoimmune diseases, cancer, allergy and infection ( Arron and Choi 2000 ; Kim et alabama. 2007a ). In particular, preliminary studies have shown large evidence supporting the complex interaction between the immune system and the tumor ( Marcus et alabama. 2014 ). A count of unconditioned system immunomodulators have been identified ; these include cytokines ( interleukins, interferons, and chemokines ), substances isolated from microorganisms and fungi ( lipopolysaccharide ), and substances isolated from plants ( polysaccharides and phenolic resin compounds ) ( Schepetkin et aluminum. 2009 ). In case of a tumor, tumor cells secrete the alter protein products that must be recognized as foreign by the immune effector cells such as B, T, natural killer whale and natural killer T cells, and type I and II interferons, and perforin which are able destroy tumor cells ( Kim et alabama. 2007b ; Hendry et alabama. 2016 ). consequently, the enhancement of host immune response is one of the most important methods for inhibiting tumor growth and maintaining cellular homeostasis without harming the host. Song et aluminum. ( 2013 ) evaluated the immunomodulatory effect of S. japonicus acid mucopolysaccharide ( SJAMP ) in an experimental hepatocellular carcinoma mannequin in rats. Rats were divided into five groups such as normal control, tumor control condition, low-SJAMP-dose ( 17.5 mg/kg ), medium-SJAMP-dose ( 35 mg/kg ) and high-SJAMP-dose ( 70 mg/ml ). The results showed that SJAMP treatment groups had significantly reduced nodule volume and nodule number, serum α-fetoprotein degree, proliferating cell nuclear antigen formulation, IL-2 and TNF-α, and increased levels of p21 expression. In addition, SJAMP recovered CD3+, CD4+, CD8+ and CD4+/CD8+ on peripheral rake T-lymphocyte subsets. In another discipline, Cao et aluminum. ( 2017 ) extracted water soluble protein-sulfated fucan ( PSF ) complex from the soundbox wall of S. japonicus and examined the immunomodulatory action in RAW264.7 cells. The backbone structure of PSF was elucidated ( 1 → 3 ) -α-L-linked fucosyl remainder with sulfation at C-2 and/or C-4 by GC-MS and 2D–NMR. It has been shown that PSF and fractions importantly induced the messenger rna formulation of iNOS and cytokines generation including IL-6, IL-10, TNF-α, and COX-2. Therefore, SJAMP can potentially provide the treatment and prevention of human diseases such as cancer and allergic disorders through immunomodulatory action .
Proliferative effect
regulation of cell proliferation plays a key character in treatment of respective diseases or in tissue positive feedback. Some studies support that ocean cucumber regulates the cell proliferation. The cell viability and proliferation effects of sulfate polysaccharide ( HS ) in neural stem/progenitor cell ( NSC ) were demonstrated by Zhang et alabama. ( 2010b ). The HS was extracted from S. japonicus by enzymolysis and subjected to fractionation by anion-exchange and gel-permeation chromatography. The average molecular weight of SJP was determined to be 4.23 × 105 Da by analytic HPLC. SJP consist of 38.12 % fucose, 16.52 % uronic acid, 32.64 % sulfate group and small amounts of galactose. The results showed that HS treatment with or without fibroblast growth factor-2 ( FGF-2 ) increased NSC proliferation in a dose-dependent manner at concentrations of 200, 500 and 800 ng/ml without apoptosis. In another study, Sheng et alabama. ( 2011 ) demonstrated the morphologic transformation and proliferation of rat astrocytes by HS ( 4.23 × 105 Da ). Results demonstrated that although HS or FGF-2 alone did not show meaning cellular telephone proliferation, combination of HS and FGF-2 importantly induced astrocytes geomorphologic transformation, cell proliferation and cyclin D1 expression. In addition, Park et alabama. ( 2012 ) investigated cell proliferation by PSC from S. japonicus in comparison with scab PSC and bovine gelatin in HaCaT keratinocyte. In the cell migration assay, sea cucumber PSC coated plates induced more cell migration than gelatin coated plates or a non-coated plate, but like to rat collagen coated plates. In addition, ocean cucumber PSC enhanced fibronectin messenger rna expression compared to that by denounce collagen and gelatin. These results suggest that sea cucumber might be utilitarian as an option to mammal collagen and could be used for cell therapy in pharmaceutical industries .
Neural related activities
The mammalian central anxious system ( CNS ) is arguably one of the most complex systems in nature ( Cao et aluminum. 2006 ). wound to the adult CNS is devastating because adult mammalian neurons do not regrow functional axons after damage and can lead to neural degeneracy and cell death ( Horner and Gage 2000 ). The CNS disorders such as Parkinson ’ second disease, Huntington ’ mho disease, and stroke are induced by multiple genetic, environmental and other factors such as aging ( Kazantsev and Thompson 2008 ). The NSC can treat the chronic injury of boldness as it can differentiate into mature neurons and glial cell lines and possess self-renewal ability ( Cui et alabama. 2016b ). therefore, NSC is a major campaigner for cell surrogate therapy for diverse intractable CNS disorders. Kaneko et alabama. ( 2003 ) isolated a new neuritogenic active voice ganglioside from n-hexane fraction of chloroform/methanol extracts of S. japonicus and elucidated its chemical structure by GC-MS and NMR spectrum. The chemical structure of new ganglioside was elucidated NeuAcα2 → 4 ( NeuAcα2 → 3 ) Galβ1 → 8NeuAcα2 → 3GalNAcβ1 → 3Galβ1 → 4Glcβ1 → 1Cer. The new ganglioside was more neuritogenic than mammal ganglioside in the rat pheochromocytoma cell argumentation ( PC12 cells ). In another study, SJP ( 4.23 × 105 Da ) evaluated the NSC proliferation and neurosphere constitution by Zhang et alabama. ( 2010a ). The results showed that SJP promotes the neurosphere formation by activating nuclear agent NF-κB in NSCs. similarly, Sheng et alabama. ( 2012 ) extracted the sulfate polysaccharide from the S. japonicus ( SJP ) body rampart and tested migration and specialization of NSC. The average molecular weight of SJP was determined to be 1.79 × 105 Da by HPSEC analysis. These results demonstrated that SJP treatment induced neurosphere adhesiveness migration by up-regulation of N-cadherin and differentiation through the PI3K/Akt signaling nerve pathway. Cui et aluminum. ( 2016c ) evaluated NSC migration effect of SJP ( 1.79 × 105 Da ). The consequence showed that SJP treatment with SDF-1α/CXCR4 axis significantly induced the construction of MMP-2 and MMP-9 proteins and promoted NSC migration from the neurosphere through the PI3K/Akt/FOXO3a, ERK/MAPK and NF-κB sign pathways. similarly, three types of polysaccharides including SJP ( 1.79 × 105 Da ), fucoidan and heparin have been demonstrated in the NSC migration by Cui et aluminum. ( 2016b ). The results demonstrate that SJP, fucoidan and heparin treatment with SDF-1α promoted NSC migration through the activation of PI3K/Akt/FOXO3a signaling pathway. consequently, these polysaccharides can potentially be used for NSC cellular telephone therapy. The neuroprotective effect of SJP was investigated in a human dopaminergic neuroblastoma cell line ( SH-SY5Y ) by Cui et alabama. ( 2016a ). They demonstrated that SJP inhibited cellular telephone death by 6-OHDA in SH-SY5Y through the prohibition of MAPK and NF-κB and the activation of PI3K/Akt signaling nerve pathway in a dose-dependent manner at the concentrations of 75, 150 and 300 μg/ml without cytotoxicity. In addition, Cui et alabama. ( 2015 ) investigated the security effect of SJP on Na2S2O4-induced hypoxia/reoxygenation ( H/R ) injury in the PC12 cell line. In Na2S2O4-induced cell cytotoxicity, SJP treatment at 500 μg/ml induced cell viability to 64.7 % as compared to the control cell viability of 46.8 %. furthermore, SJP treatment significantly reduced the Bax/Bcl-2 ratio, cleaved caspase-3/caspase-3, p53 phosphorylation and cytochrome hundred free, and suppressed the activation of MAPKs such as JNK1/2 and p38 MAPK in a dose-dependent manner at 100, 300 and 500 μg/ml. In another study, Shida et aluminum. ( 2017 ) extracted fucosylayed chondroitin sulfate ( FCS ) and examined neurite outgrowth-promoting bodily process compared with shark cartilage CS-C [ GlcA-GalNAc ( 4, 6- O -disulfate ) ] ( 0.5 % ) and squid cartilage CS-E [ GlcA-GalNAc ( 4, 6- O -disulfate ) ] ( 68 % ). FCS consists of disulfated E unit of measurement [ GlcA-GalNAc ( 4, 6- O -disulfate ) ] ( 48 % ), monosulfated units C [ GlcA-GalNAc ( 6- O -sulfated ) ] ( 28 % ), monosulfated units A [ GlcA-GalNAc ( 4-O-sulfate ) ] ( 12 % ), and non-sulfated unit O [ GlcA-GalNAc ] ( 12 % ). The results show that FCS exhibited higher neurite outgrowth-promoting activeness than CS-C. Thus, SJP could be a potential novel curative target for the treatment of CNS disorders with fewer side effects .
Biomedical application
tissue engineering is an emerging multidisciplinary science that incorporates the rationale of engineering, biochemistry, and biological sciences. The purpose of the weave mastermind is to restore, assert, improve, or replace tissues and organs function of injury or disease tissues and organs. In tissue engineering, the scaffold is one of the most authoritative factors to provide a quad for cell fastening, proliferation, specialization and weave geological formation. therefore, a scaffold must have an interconnected stoma net, optimum concentrate size for tissue ingrowth, biocompatibility, hydrophilicity for cell-scaffold interaction and non-toxicity ( Cai et alabama. 2002 ; Li et alabama. 2005 ). The polymer excerpt for scaffold fabrication should be cautiously considered because the mechanical or physiologic properties depend on different types of polymer ( Gunn and Zhang 2010 ). polymer can be divided into natural polymer and man-made polymer. Among the natural polymers, collagen is the independent component of extracellular matrix that contributes to mechanical property of cellular environments such as tissues and organs and constitutes approximately 30 % of total proteins in the animal torso ( Pati et alabama. 2010 ). At least 29 unique collagen types ( type I to XXIX ) are encoded by at least 44 genes and determined by domains that required for repeating amino acid practice of the Gly-X-Y triple coiling domain ( Schegg et aluminum. 2009 ; Chandika et aluminum. 2016 ). commercial collagen is normally isolated from land-animal tissue origin, such as bovine and hoggish skins and has been used for respective industrial application such as food, cosmetic, pharmaceutical and biomedical products because of its excellent biocompatibility, biodegradability and non-immunogenicity ( Chen et alabama. 2010 ; Liu et alabama. 2012a ). however, the collagen from land-derived animal has shown to be contaminated with the infectious agents causing diseases such as bovine spongiform brain disorder ( BSE ), catching spongiform brain disorder ( TSE ) and foot-and-mouth disease ( FMD ). therefore, versatile studies have focused on the origin of marine-derived collagen and have characterized its properties as a good alternative to land-animal collagen because marine species do not promote zoonosis in humans ( Uriarte-Montoya et alabama. 2010 ; Muralidharan et aluminum. 2013 ). The body wall of sea cucumber is a major edible depart. The body wall proteins consist of 70 % insoluble collagen and 30 % non-collagenous fibers ( Wu et aluminum. 2013 ). Saito et alabama. ( 2002 ) isolated PSC from S. japonicus consistency wall and characterize it by amino acerb writing and SDS-PAGE. The amino acid composition showed that glycine, hydroxyproline, and hydroxylysine are the major components in the collagen. They besides showed that PSC from S. japonicus was exchangeable to, but slightly different from the collagens from ocean urchin and starfish. In another study, Cui et alabama. ( 2007 ) isolated PSC from S. japonicus consistency wall and characterized it in comparison with calf hide type I collagen. The word picture was investigated by amino acidic compositions, UV-Vis spectrum, SDS-PAGE patterns, peptide map and differential gear read calorimetry ( DSC ). They reported that although PSC has different peptide map and lower thermal constancy temperature due to the different amino compositions as compared to calf clamber type I collagen, it might be a utilitarian option to land-derived type I collagen because of being closer to that of calf bark collagen. Sulfated polysaccharides have diverse functions such as development, cell differentiation, cell adhesiveness, cell signaling and cell matrix interactions due to their bind ability with proteins in the tissues ( Senni et aluminum. 2011 ). therefore, they have been found an crucial function in pharmaceutical and biomedical lotion. Among the sulfate polysaccharides, fucoidan contains significant percentages of L-fucose and sulfate ester groups and can be extracted from several algae or marine invertebrates such as ocean cucumber or sea urchin ( Li et aluminum. 2008, Holtkamp et alabama. 2009 ). The structure of fucoidan chiefly consists of a backbone of α ( 1 → 3 ) – and α ( 1 → 4 ) -linked α-l-fucopyranose residues, which may be substituted with sulfate on the C-2 or/and C-3, C-4 ( Ale and Meyer 2013 ). The fucoidans play an important character in several biological functions including anticancer and immunomodulatory, antithrombotic and anticoagulant, anti-inflammation and antioxidant effects ( Ale et alabama. 2011 ).
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Yu et alabama. ( 2015b ) isolated the fucoidan from A, japonicus ( Aj-FUC ) and tested the rheologic characteristics in comparison with sea cucumber Acaudina molpadioides fucoidan ( Am-FUC ). The chemical social organization of Aj-FUC was chiefly consists of a fresh repeating unit [ α–l–Fuc p 2 ( OSO3 − ) –1 → 3, ( α–l–Fuc p –1 → 4–α–l–Fuc p -1→ ) 4–α–l–Fuc p 2 ( OSO3 − ) –1 → 3–α–l–Fuc p 2 ( OSO3 − ) ]. The molecular burden of Aj-FUC was determined to be 1970 kDa with a content of 23.2 ± 3.7 %. Aj-FUC has lower viscosity than Am-FUC at the like concentration and fleece rate. These results suggested that repeated branched unit might importantly influence the rheologic characteristics of fucoidan .
Economic value of sea cucumber
In the late decades, invertebrate fisheries have expanded in catch and rate worldwide ( Anderson et alabama. 2011 ). Among the invertebrates, sea cucumber capture is exported to Hong Kong or nearby asian countries and the ocean cucumbers has risen dramatically in late decades due to their likely health benefits to humans in the food, pharmaceutical and biomedical industrial areas ( FAO 2008 ). On explanation of this reason, sea cucumber habitat and population are declining because of coastal fisheries befoulment, and overfishing. Therefore, sea cucumber aquaculture and management is besides one of the most significant topic for solving of ocean cucumber overfishing. In case of ocean cucumber S. japonicus, many researchers extracted versatile compound and biological extracts and investigated versatile biological activities related human health. however, hush electric potential exists to isolate and identify raw biological compounds from S. japonicus. consequently, there is a indigence to in full identify and characterize the visibility of new biological compounds from S. japonicus .
