ABSTRACT
Eight sulfated triterpene glycosides, peronioside A (1) and psolusosides A (2), B (3), G (4), I (5), L (6), N (7) and P (8), were isolated from the sea cucumber Psolus peronii. Peronioside A (1) is a new glycoside, while compounds 2-8 were found previously in Psolus fabricii, indicating the phylogenetic and systematic closeness of these species of sea cucumbers. The activity of 1-8 against human erythrocytes and their cytotoxicity against the breast cancer cell lines MCF-7, T-47D and triple-negative MDA-MB-231 were tested. The most active against cancer cell compounds, psolusosides A (2) and L (6), which were not cytotoxic to the non-transformed cells of the mammary gland, were chosen to study the inhibition of the migration, formation and growth of colonies of the cancer cell lines. Glycoside 2 effectively inhibited the growth of colonies and the migration of the MDA-MB-231 cell line. Compound 6 blocked the growth of colonies of T-47D cells and showed a pronounced antimigration effect on MDA-MB-231 cells. The quantitative structure-activity relationships (QSAR) indicated the strong impact on the activity of the form and size of the molecules, which is connected to the length and architecture of the carbohydrate chain, the distribution of charge on the molecules' surface and various aspects of hydrogen bond formation, depending on the quantity and positions of the sulfate groups. The QSAR calculations were in good accordance with the observed SAR tendencies.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Glycosides , Quantitative Structure-Activity Relationship , Sea Cucumbers , Triterpenes , Humans , Glycosides/pharmacology , Glycosides/chemistry , Glycosides/isolation & purification , Animals , Triterpenes/pharmacology , Triterpenes/chemistry , Triterpenes/isolation & purification , Sea Cucumbers/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Female , MCF-7 Cells , Cell Movement/drug effects , Erythrocytes/drug effectsABSTRACT
Sea cucumber viscera contain various naturally occurring active substances, but they are often underutilized during sea cucumber processing. Polydeoxyribonucleotide (PDRN) is an adenosine A2A receptor agonist that activates the A2A receptor to produce various biological effects. Currently, most studies on the activity of PDRN have focused on its anti-inflammatory, anti-apoptotic, and tissue repair properties, yet relatively few studies have investigated its antioxidant activity. In this study, we reported for the first time that PDRN was extracted from the sperm of Apostichopus japonicus (AJS-PDRN), and we evaluated its antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and hydroxyl radical scavenging assays. An in vitro injury model was established using H2O2-induced oxidative damage in RAW264.7 cells, and we investigated the protective effect of AJS-PDRN on these cells. Additionally, we explored the potential mechanism by which AJS-PDRN protects RAW264.7 cells from damage using iTRAQ proteomics analysis. The results showed that AJS-PDRN possessed excellent antioxidant activity and could significantly scavenge DPPH, ABTS, and hydroxyl radicals. In vitro antioxidant assays demonstrated that AJS-PDRN was cytoprotective and significantly enhanced the antioxidant capacity of RAW264.7 cells. The results of GO enrichment and KEGG pathway analysis indicate that the protective effects of AJS-PDRN pretreatment on RAW264.7 cells are primarily achieved through the regulation of immune and inflammatory responses, modulation of the extracellular matrix and signal transduction pathways, promotion of membrane repair, and enhancement of cellular antioxidant capacity. The results of a protein-protein interaction (PPI) network analysis indicate that AJS-PDRN reduces cellular oxidative damage by upregulating the expression of intracellular selenoprotein family members. In summary, our findings reveal that AJS-PDRN mitigates H2O2-induced oxidative damage through multiple pathways, underscoring its significant potential in the prevention and treatment of diseases caused by oxidative stress.
Subject(s)
Antioxidants , Hydrogen Peroxide , Oxidative Stress , Polydeoxyribonucleotides , Proteomics , Spermatozoa , Animals , Mice , Hydrogen Peroxide/toxicity , Proteomics/methods , Male , Antioxidants/pharmacology , Antioxidants/isolation & purification , Oxidative Stress/drug effects , Spermatozoa/drug effects , Spermatozoa/metabolism , RAW 264.7 Cells , Polydeoxyribonucleotides/pharmacology , Stichopus/chemistry , Sea Cucumbers/chemistry , Protective Agents/pharmacologyABSTRACT
Sea cucumber phospholipids have ameliorative effects on various diseases related to lipid metabolism. However, it is unclear whether it can ameliorate obesity-associated glomerulopathy (ORG) induced by a high-fat diet (HFD). The present study applied UPLC-QqQ-MS/MS and atmospheric pressure matrix-assisted laser desorption ionization mass spectrometry imaging (AP-MALDI MSI) to investigate the effects of sea cucumber phospholipids, including plasmalogen PlsEtn and plasmanylcholine PakCho, on phospholipid profiles in the HFD-induced ORG mouse kidney. Quantitative analysis of 135 phospholipids revealed that PlsEtn and PakCho significantly modulated phospholipid levels. Notably, PlsEtn modulated kidney overall phospholipids better than PakCho. Imaging the "space-content" of 9 phospholipids indicated that HFD significantly increased phospholipid content within the renal cortex. Furthermore, PlsEtn and PakCho significantly decreased the expression of transport-related proteins CD36, while elevating the expression of fatty acid ß-oxidation-related protein PPAR-α in the renal cortex. In conclusion, sea cucumber phospholipids reduced renal lipid accumulation, ameliorated renal damage, effectively regulated the content and distribution of renal phospholipids, and improved phospholipid homeostasis, exerting an anti-OGR effect.
Subject(s)
Kidney , Mice, Inbred C57BL , Obesity , Phospholipids , Sea Cucumbers , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Tandem Mass Spectrometry , Animals , Sea Cucumbers/chemistry , Sea Cucumbers/metabolism , Mice , Phospholipids/metabolism , Phospholipids/chemistry , Kidney/metabolism , Kidney/chemistry , Tandem Mass Spectrometry/methods , Male , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Chromatography, High Pressure Liquid/methods , Obesity/metabolism , Humans , Diet, High-Fat/adverse effects , Mice, Obese , Kidney Diseases/metabolismABSTRACT
BACKGROUND: The holothurians, commonly known as sea cucumbers, are marine organisms that possess significant dietary, nutritional, and medicinal value. However, the National Center for Biotechnology Information (NCBI) currently possesses only approximately 70 complete mitochondrial genome datasets of Holothurioidea, which poses limitations on conducting comprehensive research on their genetic resources and evolutionary patterns. In this study, a novel species of sea cucumber belonging to the genus Benthodytes, was discovered in the western Pacific Ocean. The genomic DNA of the novel sea cucumber was extracted, sequenced, assembled and subjected to thorough analysis. RESULTS: The mtDNA of Benthodytes sp. Gxx-2023 (GenBank No. OR992091) exhibits a circular structure spanning 17,386 bp, comprising of 13 protein-coding genes (PCGs), 24 non-coding RNAs (2 rRNA genes and 22 tRNA genes), along with two putative control regions measuring 882 bp and 1153 bp, respectively. It exhibits a high AT% content and negative AT-skew, which distinguishing it from the majority of sea cucumbers in terms of environmental adaptability evolution. The mitochondrial gene homology between Gxx-2023 and other sea cucumbers is significantly low, with less than 91% similarity to Benthodytes marianensis, which exhibits the highest level of homology. Additionally, its homology with other sea cucumbers is below 80%. The mitogenome of this species exhibits a unique pattern in terms of start and stop codons, featuring only two types of start codons (ATG and ATT) and three types of stop codons including the incomplete T. Notably, the abundance of AT in the Second position of the codons surpasses that of the First and Third position. The gene arrangement of PCGs exhibits a relatively conserved pattern, while there exists substantial variability in tRNA. Evolutionary analysis revealed that it formed a distinct cluster with B. marianensis and exhibited relatively distant phylogenetic relationships with other sea cucumbers. CONCLUSIONS: These findings contribute to the taxonomic diversity of sea cucumbers in the Elasipodida order, thereby holding significant implications for the conservation of biological genetic resources, evolutionary advancements, and the exploration of novel sea cucumber resources.
Subject(s)
Evolution, Molecular , Genome, Mitochondrial , Phylogeny , Sea Cucumbers , Animals , Sea Cucumbers/genetics , RNA, Transfer/genetics , Base CompositionABSTRACT
Effective crosslinking among food constituents has the potential to enhance their overall quality. Distarch phosphate (DSP), a common food additive employed as a thickening agent, bears a pre-crosslinked oligosaccharide (PCO) moiety within its molecular structure. Once this moiety is released, its double reducing end has the potential to undergo crosslinking with amino-rich macromolecules through Maillard reaction. In this study, hydrolyzed distarch phosphate (HDSP) was synthesized, and spectroscopic analysis verified the presence of PCO within HDSP. Preliminary validation experiment showed that HDSP could crosslink chitosan to form a hydrogel and significant browning was also observed during the process. Furthermore, rehydrated sea cucumber (RSC) crosslinked with HDSP exhibited a more intact appearance, higher mechanical strength, better color profile, and increased water-holding capacity. This series of results have confirmed that HDSP is capable to crosslink amino-rich macromolecules and form more stable three-dimensional network.
Subject(s)
Phosphates , Sea Cucumbers , Animals , Sea Cucumbers/chemistry , Hydrolysis , Phosphates/chemistry , Food Additives/chemistry , Cross-Linking Reagents/chemistry , Maillard Reaction , Oligosaccharides/chemistryABSTRACT
The natural flavor of sea cucumber is generally not easily accepted by consumers. In this study, the effect of different cooking conditions on the adsorption of the characteristic flavor of Sichuan pepper by sea cucumber was investigated by response surface methodology, and the optimal cooking conditions were identified. A total of 45 volatiles were identified based on gas chromatography-mass spectrometry, of which 27 were key flavor actives. Low-field nuclear magnetic resonance and textural analysis showed that the addition of Sichuan pepper during the cooking process affected the water migration and the textural properties of sea cucumbers. It was shown that the addition of Sichuan pepper could significantly improve the flavor and other quality characteristics of sea cucumber. This study has important practical guiding significance for the flavor improvement and product innovation of sea cucumber food.
Subject(s)
Cooking , Gas Chromatography-Mass Spectrometry , Sea Cucumbers , Volatile Organic Compounds , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/analysis , Animals , Sea Cucumbers/chemistry , Adsorption , Taste , Flavoring Agents/chemistryABSTRACT
Three polysaccharides (SnNG, SnFS and SnFG) were purified from the body wall of Stichopus naso. The physicochemical properties, including monosaccharide composition, molecular weight, sulfate content, and optical rotation, were analyzed, confirming that SnFS and SnFG are sulfated polysaccharides commonly found in sea cucumbers. The highly regular structure {3)-L-Fuc2S-(α1,}n of SnFS was determined via a detailed NMR analysis of its oxidative degradation product. By employing ß-elimination depolymerization of SnFG, tri-, penta-, octa-, hendeca-, tetradeca-, and heptadeca-saccharides were obtained from the low-molecular-weight product. Their well-defined structures confirmed that SnFG possessed the backbone of {D-GalNAc4S6S-ß(1,4)-D-GlcA}, and each GlcA residue was branched with Fuc2S4S. SnFS and SnFG are both structurally the simplest version of natural fucan sulfate and fucosylated glycosaminoglycan, facilitating the application of low-value sea cucumbers S. naso. Bioactivity assays showed that SnFG and its derived oligosaccharides exhibited potent anticoagulation and intrinsic factor Xase (iXase) inhibition. Moreover, a comparative analysis with the series of oligosaccharides solely branched with Fuc3S4S showed that in oligosaccharides with lower degrees of polymerization, such as octasaccharides, Fuc2S4S led to a greater increase in APTT prolongation and iXase inhibition. As the degree of polymerization increases, the influence from the sulfation pattern diminishes, until it is overshadowed by the effects of molecular weight.
Subject(s)
Anticoagulants , Molecular Weight , Oligosaccharides , Polysaccharides , Animals , Anticoagulants/pharmacology , Anticoagulants/chemistry , Anticoagulants/isolation & purification , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Oligosaccharides/isolation & purification , Stichopus/chemistry , Sea Cucumbers/chemistry , Sulfates/chemistry , Magnetic Resonance Spectroscopy , Blood Coagulation/drug effectsABSTRACT
Sulfated fucan from sea cucumber is mainly consists of L-fucose and sulfate groups. Recent studies have confirmed that the structure of sulfated fucan mainly consists of repeating units, typically tetrasaccharides. However, there is growing evidence indicating the presence of irregular domains with heterogeneous units that have not been extensively explored. Moreover, as a key contributor to the nutritional benefits of sea cucumbers, sulfated fucan demonstrates a range of biological activities, such as anti-inflammatory, anticancer, hypolipidemic, anti-hyperglycemic, antioxidant, and anticoagulant properties. These biological activities are profoundly influenced by the structural features of sulfated fucan including molecular weight and distribution patterns of sulfate groups. The latest research indicates that sulfated fucan is dispersed in the extracellular matrix of the body wall of sea cucumbers. This article aimed to review the research progress on the in-situ distribution, structures, structural elucidation strategies, functions, and structure-activity relationships of sulfated fucan, especially in the last decade. It also provided insights into the major challenges and potential solutions in the research and development of sulfated fucan. Moreover, the fucanase and carbohydrate binding modules are anticipated to play pivotal roles in advancing this field.
Subject(s)
Polysaccharides , Sea Cucumbers , Sea Cucumbers/chemistry , Animals , Polysaccharides/chemistry , Polysaccharides/pharmacology , Structure-Activity Relationship , Sulfates/chemistry , Anticoagulants/chemistry , Anticoagulants/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Humans , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacologyABSTRACT
More than 40 volatile compounds were detected in sea cucumber powder during the processing (through freeze-dried, desalination, supercritical fluid extraction and ultra-micro grinding) by multiple methods including e-nose, GC-IMS and GC-MS. It has been determined that aldehydes are the predominant volatile substances in the original freeze-dried sample, accounting for about 30 % of the total volatile substances. In addition, we established a supercritical fluid extraction strategy that could efficiently remove the aldehydes from the sea cucumber powder. GC-IMS and GC-MS showed that the relative content of aldehydes significantly decreased by 14 % and 28 %, respectively. Quantification of aldehydes using GC-MS showed a significant decrease in octanal from 927 µg/kg to 159 µg/kg. Further investigation combined with OAV analysis showed that 17 volatile substances in the freeze-dried sea cucumber powder were considered to be the predominant volatile compounds (OAV > 1).The primary fishy compounds found in sea cucumber powder were identified as hexanal, octanal, and an unidentified compound using GC-O, which can be effectively removed (OAV can't been estimated) by the supercritical fluid extraction strategy we established.
Subject(s)
Chromatography, Supercritical Fluid , Food Handling , Gas Chromatography-Mass Spectrometry , Powders , Sea Cucumbers , Volatile Organic Compounds , Chromatography, Supercritical Fluid/methods , Sea Cucumbers/chemistry , Volatile Organic Compounds/analysis , Volatile Organic Compounds/isolation & purification , Animals , Food Handling/methods , Freeze Drying , Aldehydes/analysis , Aldehydes/isolation & purification , Electronic Nose , Seafood/analysisABSTRACT
Sea cucumbers, members of the echinoderm class Holothuroidea, are marine invertebrates with ecological significance and substantial commercial value. With approximately 1700 species, these organisms contribute to marine ecosystems through nutrient cycling and face various threats, including overfishing and habitat loss. Despite their importance, they are extensively exploited for diverse applications, from seafood to pharmaceuticals. This study investigates sea cucumbers' nutritional profile and bioactive elements, emphasizing their role as sources of essential compounds with potential health benefits. The demand for sea cucumbers, especially in dried form, is significant, prompting exploration into various drying techniques. Examining the global trade in sea cucumbers highlights their economic importance and the conservation challenges they face. Conservation efforts, such as awareness campaigns and international collaboration, are evaluated as essential steps in combating illicit trade and promoting the sustainable stewardship of sea cucumber populations. PRACTICAL APPLICATION: Around 1700 species of sea cucumbers were identified as vital ecological scavengers in the Holothuroidea class. High commercial value due to their health benefits, particularly their demonstrated inhibitory effect against various types of cancer. "Beche-de-mer" holds a 90% market share and is regarded as a luxury food item in Southeast Asian countries. Due to overexploitation, the species is classified as Schedule I under the Wildlife Protection Act (WPA) in India, prompting the implementation of a blanket ban on their harvesting to ensure its conservation.
Subject(s)
Desiccation , Sea Cucumbers , Seafood , Sea Cucumbers/chemistry , Animals , India , Desiccation/methods , Seafood/analysis , Nutritive Value , Food Handling/methodsABSTRACT
Due to the dramatic reduction of sea cucumber Isostichopus badionotus populations in the Yucatan Peninsula by overfishing and poaching, aquaculture has been encouraged as an alternative to commercial catching and restoring wild populations. However, the scarcity of broodstock, the emergence of a new disease in the auricularia larvae stage, and the development of skin ulceration syndrome (SUS) in the culture have limited aquaculture development. This study presents the changes in the intestine and skin microbiota observed in early and advanced stages of SUS disease in cultured juvenile I. badionotus obtained during an outbreak in experimental culture through 16S rRNA gene sequencing and histological evidence. Our results showed inflammation in the intestines of juveniles at both stages of SUS. However, more severe tissue damage and the presence of bacterial clusters were detected only in the advanced stages of SUS. Differences in the composition and structure of the intestinal and skin bacterial community from early and advanced stages of SUS were detected, with more evident changes in the intestinal microbial communities. These findings suggest that SUS was not induced by a single pathogenic bacterium. Nevertheless, a decrease in the abundance of Vibrio and an increase in Halarcobacter (syn. Arcobacter) was observed, suggesting that these two bacterial groups could be keystone genera involved in SUS disease.
Subject(s)
Microbiota , Sea Cucumbers , Skin , Animals , Skin/microbiology , Skin/pathology , Sea Cucumbers/microbiology , Aquaculture , RNA, Ribosomal, 16S/genetics , Skin Ulcer/microbiology , Skin Ulcer/epidemiology , Skin Ulcer/pathology , Disease Outbreaks , Gastrointestinal MicrobiomeABSTRACT
Thromboembolic diseases pose a serious risk to human health worldwide. Fucosylated chondroitin sulfate (FCS) is reported to have good anticoagulant activity with a low bleeding risk. Molecular weight plays a significant role in the anticoagulant activity of FCS, and FCS smaller than octasaccharide in size has no anticoagulant activity. Therefore, identifying the best candidate for developing novel anticoagulant FCS drugs is crucial. Herein, native FCS was isolated from sea cucumber Cucumaria frondosa (FCScf) and depolymerized into a series of lower molecular weights (FCScfs). A comprehensive assessment of the in vitro anticoagulant activity and in vivo bleeding risk of FCScfs with different molecule weights demonstrated that 10 kDa FCScf (FCScf-10 K) had a greater intrinsic anticoagulant activity than low molecular weight heparin (LMWH) without any bleeding risk. Using molecular modeling combined with experimental validation, we revealed that FCScf-10 K can specifically inhibit the formation of the Xase complex by binding the negatively charged sulfate group of FCScf-10 K to the positively charged side chain of arginine residues on the specific surface of factor IXa. Thus, these data demonstrate that the intermediate molecular weight FCScf-10 K is a promising candidate for the development of novel anticoagulant drugs.
Subject(s)
Anticoagulants , Chondroitin Sulfates , Factor IXa , Molecular Weight , Animals , Chondroitin Sulfates/chemistry , Chondroitin Sulfates/pharmacology , Chondroitin Sulfates/isolation & purification , Anticoagulants/pharmacology , Anticoagulants/chemistry , Anticoagulants/isolation & purification , Factor IXa/metabolism , Factor IXa/antagonists & inhibitors , Factor IXa/chemistry , Cucumaria/chemistry , Sea Cucumbers/chemistry , Blood Coagulation/drug effects , Humans , Models, MolecularABSTRACT
Since oxidative stress is often associated with neurodegenerative diseases, antioxidants are likely to confer protection against neurodegeneration. Despite an increasing number of food-derived peptides being identified as antioxidants, their antineurodegenerative potentials remain largely unexplored. Here, a sea cucumber peptide preparation - the peptide-rich fraction of <3 kDa (UF<3K) obtained by ultrafiltration from Apostichopus japonicus protein hydrolyzate - was found to protect PC12 cells and Caenorhabditis elegans from neurodegeneration by reducing oxidative stress and apoptosis, demonstrating its in vitro and in vivo neuroprotective effects. As many food-originated peptides are cryptides (cryptic peptides - short amino acid sequences encrypted in parent proteins) released in quantities by protein hydrolysis, UF<3K was subjected to sequencing analysis. As expected, a large repertoire of peptides were identified in UF<3K, establishing a sea cucumber cryptome (1238 peptides in total). Then 134 peptides were randomly selected from the cryptome (>10%) and analyzed for their antioxidant activities using a number of in silico bioinformatic programs as well as in vivo experimental assays in C. elegans. From these results, a novel antioxidant peptide - HoloPep#362 (FETLMPLWGNK) - was shown to not only inhibit aggregation of neurodegeneration-associated polygluatmine proteins but also ameliorate behavioral deficits in proteotoxicity nematodes. Proteomic analysis revealed an increased expression of several lysosomal proteases by HoloPep#362, suggesting proteostasis maintenance as a mechanism for its antineurodegenerative action. These findings provide an insight into the health-promoting potential of sea cucumber peptides as neuroprotective nutraceuticals and also into the importance of training in silico peptide bioactivity prediction programs with in vivo experimental data.
Subject(s)
Antioxidants , Caenorhabditis elegans , Neuroprotective Agents , Oxidative Stress , Peptides , Sea Cucumbers , Animals , Caenorhabditis elegans/drug effects , Antioxidants/pharmacology , Antioxidants/chemistry , Peptides/pharmacology , Peptides/chemistry , Sea Cucumbers/chemistry , Oxidative Stress/drug effects , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , PC12 Cells , Rats , Neurodegenerative Diseases/drug therapy , Computer SimulationABSTRACT
Caspase (CASP) is a protease family that plays a vital role in apoptosis, development, and immune response. Herein, we reported the identification and characterization of two CASPs, AjCASPX1 and AjCASPX2, from the sea cucumber Apostichopus japonicus, an important aquaculture species. AjCASPX1/2 share similar domain organizations with the vertebrate initiator caspases CASP2/9, including the CARD domain and the p20/p10 subunits with conserved functional motifs. However, compared with human CASP2/9, AjCASPX1/2 possess unique structural features in the linker region between p20 and p10. AjCASPX1, but not AjCASPX2, induced marked apoptosis of human cells by activating CASP3/7. The recombinant proteins of AjCASPX2 and the CARD domain of AjCASPX2 were able to bind to a wide range of bacteria, as well as bacterial cell wall components, and inhibit bacterial growth. AjCASPX1, when expressed in Escherichia coli, was able to kill the host bacteria. Under normal conditions, AjCASPX1 and AjCASPX2 expressions were most abundant in sea cucumber muscle and coelomocytes, respectively. After bacterial infection, both AjCASPX1 and AjCASPX2 expressions were significantly upregulated in sea cucumber tissues and cells. Together, these results indicated that AjCASPX1 and AjCASPX2 were initiator caspases with antimicrobial activity and likely functioned in apoptosis and immune defense against pathogen infection.
Subject(s)
Apoptosis , Stichopus , Animals , Stichopus/genetics , Stichopus/microbiology , Stichopus/immunology , Humans , Caspases, Initiator/genetics , Caspases, Initiator/metabolism , Sea Cucumbers/genetics , PhylogenyABSTRACT
Muscle atrophy resulting from peripheral nerve injury (PNI) poses a threat to a patient's mobility and sensitivity. However, an effective method to inhibit muscle atrophy following PNI remains elusive. Drawing inspiration from the sea cucumber, we have integrated microneedles (MNs) and microchannel technology into nerve guidance conduits (NGCs) to develop bionic microneedle NGCs (MNGCs) that emulate the structure and piezoelectric function of sea cucumbers. Morphologically, MNGCs feature an outer surface with outward-pointing needle tips capable of applying electrical stimulation to denervated muscles. Simultaneously, the interior contains microchannels designed to guide the migration of Schwann cells (SCs). Physiologically, the incorporation of conductive reduced graphene oxide and piezoelectric zinc oxide nanoparticles into the polycaprolactone scaffold enhances conductivity and piezoelectric properties, facilitating SCs' migration, myelin regeneration, axon growth, and the restoration of neuromuscular function. These combined effects ultimately lead to the inhibition of muscle atrophy and the restoration of nerve function. Consequently, the concept of the synergistic effect of inhibiting muscle atrophy and promoting nerve regeneration has the capacity to transform the traditional approach to PNI repair and find broad applications in PNI repair.
Subject(s)
Muscular Atrophy , Needles , Nerve Regeneration , Sea Cucumbers , Animals , Nerve Regeneration/drug effects , Muscular Atrophy/prevention & control , Muscular Atrophy/pathology , Sea Cucumbers/chemistry , Schwann Cells , Peripheral Nerve Injuries/pathology , Peripheral Nerve Injuries/therapy , Graphite/chemistry , Rats , Polyesters/chemistry , Rats, Sprague-Dawley , MiceABSTRACT
Fucosylated chondroitin sulfate is a unique glycosaminoglycan isolated from sea cucumbers, with excellent anticoagulant activity. The fucosyl branch in FCS is generally located at the 3-OH of D-glucuronic acid but, recently, a novel structure with α-L-fucose linked to the 6-OH of N-acetyl-galactosamine has been found. Here, using functionalized monosaccharide building blocks, we prepared novel FCS tetrasaccharides with fucosyl branches both at the 6-OH of GalNAc and 3-OH of GlcA. In the synthesis, the protective group strategy of selective O-sulfation, as well as stereoselective glycosylation, was established, which enabled the efficient synthesis of the specific tetrasaccharide compounds. This research enriches knowledge on the structural types of FCS oligosaccharides and facilitates the exploration of the structure-activity relationship in the future.
Subject(s)
Chondroitin Sulfates , Oligosaccharides , Sea Cucumbers , Chondroitin Sulfates/chemistry , Chondroitin Sulfates/chemical synthesis , Chondroitin Sulfates/pharmacology , Animals , Oligosaccharides/chemical synthesis , Oligosaccharides/chemistry , Sea Cucumbers/chemistry , Glycosylation , Fucose/chemistry , Anticoagulants/pharmacology , Anticoagulants/chemistry , Anticoagulants/chemical synthesis , Structure-Activity Relationship , Acetylgalactosamine/chemistry , Acetylgalactosamine/analogs & derivativesABSTRACT
Sea cucumber phospholipids, including the plasmalogen (PlsEtn) and plasmanylcholine (PakCho), have been shown to play a regulatory role in lipid metabolism disorders, but their mechanism of action remains unclear. Therefore, high-fat diet (HFD) and palmitic acid were used to establish lipid accumulation models in mice and HepG2 cells, respectively. Results showed that PlsEtn can reduce lipid deposition both in vivo and in vitro. HFD stimulation abnormally activated lipophagy through the phosphorylation of the AMPK/ULK1 pathway. The lipophagy flux monitor revealed abnormalities in the fusion stage of lipophagy. Of note, only PlsEtn stimulated the dynamic remodeling of the autophagosome membrane, which was indicated by the significantly decreased LC3 II/I ratio and p62 level. In all experiments, the effect of PlsEtn was significantly higher than that of PakCho. These findings elucidated the mechanism of PlsEtn in alleviating lipid accumulation, showed that it might be a lipophagy enhancer, and provided new insights into the high-value utilization of sea cucumber as an agricultural resource.
Subject(s)
Diet, High-Fat , Lipid Metabolism , Plasmalogens , Sea Cucumbers , Animals , Diet, High-Fat/adverse effects , Plasmalogens/metabolism , Sea Cucumbers/metabolism , Lipid Metabolism/drug effects , Mice , Humans , Hep G2 Cells , Male , Mice, Inbred C57BL , Autophagy/drug effectsABSTRACT
The sea cucumber plasmalogen PlsEtn has been shown to be associated with various chronic diseases related to lipid metabolism. However, the mechanism is unclear. Therefore, the present study used the sea cucumber plasmanylcholine PakCho as a structural contrast to PlsEtn and assessed its effect in 8 week high-fat diet (HFD)-fed mice. The lipidomic approach based on high-resolution mass spectrometry combined with molecular biology techniques was used to evaluate the mechanism of PlsEtn. The results showed that both PlsEtn and PakCho significantly inhibited an increase in mouse body weight and liver total triglyceride and total cholesterol levels caused by HFD. In addition, oil red O staining demonstrated that lipid droplets stored in the liver were degraded. Meanwhile, untargeted lipidomic experiments revealed that total lipids (increased by 42.8 mmol/mg prot; p < 0.05), triglycerides (increased by 38.9 mmol/mg prot; p < 0.01), sphingolipids (increased by 1.5 mmol/mg prot; p < 0.0001), and phospholipids (increased by 2.5 mmol/mg prot; p < 0.05) were all significantly elevated under HFD. PlsEtn resolved lipid metabolism disorders by alleviating the abnormal expression of lipid subclasses. In addition, five lipid molecular species, PE (18:1/20:4), PE (18:1/20:3), PE (18:1/18:3), TG (16:0/16:0/17:0), and TG (15:0/16:0/18:1), were identified as the biomarkers of HFD-induced lipid metabolism disorders. Finally, lipophagy-associated protein expression analysis showed that HFD abnormally activated lipophagy via ULK1 phosphorylation and PlsEtn alleviated lipophagy disorder through lysosomal function promotion. In addition, PlsEtn performed better than PakCho. Taken together, the current study results unraveled the mechanism of PlsEtn in alleviating lipid metabolism disorder and offered a new theoretical foundation for the high-value development of sea cucumber.
Subject(s)
Diet, High-Fat , Lipid Metabolism , Liver , Mice, Inbred C57BL , Plasmalogens , Sea Cucumbers , Triglycerides , Animals , Diet, High-Fat/adverse effects , Mice , Sea Cucumbers/chemistry , Sea Cucumbers/metabolism , Liver/metabolism , Male , Plasmalogens/metabolism , Triglycerides/metabolism , Humans , Lipids/bloodABSTRACT
With the continuous rise of the sea cucumber aquaculture industry in China, the tropical sea cucumber aquaculture industry is also improving. However, research on the gut microorganisms of tropical sea cucumbers in captivity is scarce. In this study, high-throughput sequencing methods were used to analyze the gut microbial composition of Stichopus monotuberculatus and Holothuria scabra in the dry season and wet season of artificial environments. The results showed that 66 phyla were obtained in all samples, of which 59 phyla were obtained in the dry season, and 45 phyla were obtained in the wet season. The Tax4Fun analysis showed that certain gut bacterial communities affect the daily metabolism of two sea cucumber species and are involved in maintaining gut microecological balance in the gut of two sea cucumber species. In addition, compared with differences between species, PCoA and UPGMA clustering analysis showed the gut prokaryotes of the same sea cucumber species varied more in different seasons, indicating that the influence of environment was higher than the feeding choices of sea cucumbers under relatively closed conditions. These results revealed the gut bacterial community composition of S. monotuberculatus and H. scabra and the differences in gut bacterial structure between two sea cucumber species in different seasons were compared, which would provide the foundation for tropical sea cucumber aquaculture in the future.
Subject(s)
Bacteria , Gastrointestinal Microbiome , Sea Cucumbers , Seasons , Animals , Gastrointestinal Microbiome/genetics , Bacteria/classification , Bacteria/genetics , Sea Cucumbers/microbiology , Sea Cucumbers/genetics , Aquaculture , High-Throughput Nucleotide Sequencing , Phylogeny , Holothuria/microbiology , Holothuria/genetics , Stichopus/microbiology , Stichopus/genetics , RNA, Ribosomal, 16S/geneticsABSTRACT
In this study, the effects of the thermal ultrasonic enzyme inactivation process on flavor enhancement in sea cucumber hydrolysates (SCHs) and its impact on the inactivation of neutral proteases (NPs) were investigated. The body wall of the sea cucumber was enzymatically hydrolyzed with NPs. On the one hand, the structure of NPs subjected to different enzyme inactivation methods was analyzed using ζ-potential, particle size, and Fourier transform infrared (FT-IR) spectroscopy. On the other hand, the microstructure and flavor changes of SCHs were examined through scanning electron microscopy, E-nose, and gas chromatography-ion mobility spectrometry (GC-IMS). The results indicated that thermal ultrasound treatment at 60 °C could greatly affect the structure of NPs, thereby achieving enzyme inactivation. Furthermore, this treatment generated more pleasant flavor compounds, such as pentanal and (E)-2-nonenal. Hence, thermal ultrasound treatment could serve as an alternative process to traditional heat inactivation of enzymes for improving the flavor of SCHs.