Dietary fucoidan of Acaudina molpadioides alters gut microbiota and mitigates intestinal mucosal injury induced by cyclophosphamide.[Pubmed: 28861559]

Cyclophosphamide (cy) is a widely used cancer drug. Many researchers have focused on the prevention and alleviation of its side effects, particularly damage to the intestinal mucosal barrier. In this study, we examined the effects of fucoidan, isolated from Acaudina molpadioides, on mice with intestinal mucosal damage induced by cyclophosphamide. Our results showed that fucoidan intervention could relieve injury such as decreasing inflammation and increasing the expression of tight junction proteins, and 50 kDa fucoidan significantly increased the abundance of short chain fatty acid (SCFA) producer Coprococcus, Rikenella, and Butyricicoccus (p < 0.05, p < 0.001, and p < 0.05, respectively) species within the intestinal mucosa compared with the cyclophosphamide group, as determined by 16S rDNA gene high-throughput sequencing. In addition, SCFAs, particularly propionate, butyrate, and total SCFAs, were increased in the feces, and SCFA receptors were upregulated in the small intestine. The protective effects of fucoidan on cyclophosphamide treatment may be associated with gut microflora, and 50 kDa fucoidan had superior effects. Therefore, fucoidan may have applications as an effective supplement to protect against intestinal mucosal barrier damage during chemotherapy.

Chain conformational and physicochemical properties of fucoidans from sea cucumber.[Pubmed: 27516290]

Although fucoidans from sea cucumber (SC-FUCs) have been proven as potential bioactive polysaccharides and functional food ingridents, their chain conformation and physicochemical properties were still poorly understood. This study investigated the chain conformation of fucoidans from sea cucumber Acaudina molpadioides (Am-FUC), Isostichopus badionotus (Ib-FUC) and Apostichopus japonicus (Aj-FUC), of which primary structure has been recently clarified. Chain conformation parameters demonstrated that studied SC-FUCs adopted random coil conformation in 150mM NaCl solution (pH 7.4). Based on the worm-like cylinder model and atomic force microscopy, the chain stiffness of SC-FUCs was further evaluated as Am-FUC≈Ib-FUC>Aj-FUC. It was suggested that the existence of branch structure increased the chain flexibility, while sulfated pattern exerted limited influence. SC-FUCs demonstrated shear-thinning rheological behavior and negative charge. Am-FUC possessed a higher thermostability than Ib-FUC and Aj-FUC. These results have important implications for understanding the molecular characteristics of SC-FUCs, which could facilitate their further application.

Sea cucumber cerebrosides and long-chain bases from Acaudina molpadioides protect against high fat diet-induced metabolic disorders in mice.[Pubmed: 26399628]

Metabolic syndrome (MS) is a cluster of metabolic disorders such as abdominal obesity, hypertension, glucose intolerance, dyslipidemia and hepatic steatosis that contribute to increased cardiovascular morbidity and mortality. There is an urgent need for strategies to prevent this emerging global epidemic. Recently, growing interest in discovering food functional nutrients for the prevention and treatment of MS has generated. In the present study, sea cucumber cerebrosides (SCC) and the main structural units, long-chain bases (LCB), were prepared from Acaudina molpadioides and then administered to high fat (HF) diet-induced obese C57BL/6J mice at a diet supplement dosage of 0.025% for 5 weeks to evaluate their effects on obesity-related metabolic disorders. SCC and LCB significantly decreased epididymal adipose tissue weights, lowered hepatic triacylglycerol levels, and reduced serum glucose, insulin levels and HOMA-IR index in mice. The activities of hepatic lipogenetic enzymes including FAS, ME and the mRNA levels of SREBP-1c and FAS were reduced by SCC and LCB treatment. However, SCC and LCB showed no effect on the hepatic lipolysis pathway. Besides, SCC and LCB also efficiently up-regulated the gene expression of SREBP-1c, FAS, ACC, ATGL and HSL, and down-regulated the gene expression of LPL and VLDL-r in the adipose tissue. These results demonstrated that SCC and LCB were efficacious in suppressing hepatic SREBP-1c mediated lipogenesis, inhibiting lipid uptake and increasing TG catabolism in the adipose tissue. The ameliorative degree and regulatory mechanisms of these two compounds were basically the same, suggesting that LCB are the key active structural units. Such findings would offer new insight into the application of SCC or LCB in the development of functional foods for preventing MS in humans.

Reversed-Phase Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry for High-Throughput Molecular Profiling of Sea Cucumber Cerebrosides.[Pubmed: 26037520]

Usually, the chemical structures of cerebrosides in sea creatures are more complicated than those from terrestrial plants and animals. Very little is known about the method for high-throughput molecular profiling of cerebrosides in sea cucumbers. In this study, cerebrosides from four species of edible sea cucumbers, specifically, Apostichopus japonicas, Thelenota ananas, Acaudina molpadioides and Bohadschia marmorata, were rapidly identified using reversed-phase liquid chromatography-quadrupole-time-of-flight mass spectrometry (RPLC-QToF-MS). [M + H](+) in positive electrospray ionization (ESI) mode were used to obtain the product ion spectra. The cerebroside molecules were selected according to the neutral loss fragments of 180 Da and then identified according to pairs of specific products of long-chain bases (LCB) and their precursor ions. A typical predominant LCB was 2-amino-1,3-dihydroxy-4-heptadecene (d17:1), which was acylated to form saturated and monounsaturated non-hydroxy and monohydroxy fatty acids with 17-25 carbon atoms. Simultaneously, the occurrence of 2-hydroxy-tricosenoic acid (C23:1h) was characteristic of sea cucumber cerebrosides, whereas this molecule was rarely discovered in plants, mammals, or fungi. The profiles of LCB and fatty acids (FA) distribution might be related to the genera of sea cucumber. These data will be useful for identification of cerebrosides using RPLC-QToF-MS.

Structure and rheological characteristics of fucoidan from sea cucumber Apostichopus japonicus.[Pubmed: 25766803]

Sea cucumber is a traditional health food consumed in East Asia. In this study, fucoidan from sea cucumber Apostichopus japonicus (Aj-FUC) was isolated, and its structure and rheological characteristics were elucidated for the first time. Aj-FUC was a branched polysaccharide mainly composed of a novel repeating unit [α-L-Fucp2(OSO3(-))-1 → 3,(α-L-Fucp-1 → 4-α-L-Fucp-1 →)4-α-L-Fucp2(OSO3(-))-1 → 3-α-L-Fucp2(OSO3(-))], clarified by using a combination of infrared spectroscopy, methylation analysis, enzymatic degradation and nuclear magnetic resonance. In steady shear measurement, Aj-FUC manifested a non-Newtonian shear-thinning behaviour at low shear rate (1-100 S(-1)) while exhibiting a non-Newtonian shear-thickening behaviour at high shear rate (100-1000 S(-1)); salts had limited impact on its flow curve. Comparative study on viscosity and rheological behaviour of Aj-FUC and a linear fucoidan extracted from sea cucumber Acaudina molpadioides suggested that the presence of branch structure might significantly influence the rheological characteristics of fucoidan.

Dietary fucoidan of Acaudina molpadioides and its enzymatically degraded fragments could prevent intestinal mucositis induced by chemotherapy in mice.[Pubmed: 25407449]

Mucositis is a common problem that results from cancer chemotherapy and is a cause of significant morbidity and occasional mortality. Its prevention and successful treatment can significantly enhance the quality of life of patients and improve their survival. Sea cucumber is a traditional aquatic food that has both nutritional and medicinal value. The polysaccharide fucoidan from the sea cucumber (SC-FUC) has various bioactivities. We examined the protective effect of different molecular weights (MWs 50 kDa-500 kDa) of fucoidan from the sea cucumber, Acaudina molpadioides, in a mouse model of cyclophosphamide (Cy)-induced intestinal mucositis. Results showed that the oral administration of SC-FUC markedly reversed Cy-induced damage in the mice. The sea cucumber fucoidan notably increased the ratio of the length of the intestinal villus to the crypt depth and ameliorated the IFN-γ/IL-4 ratio that signifies Th1/Th2 immune balance. Moreover, all the fucoidans in this study enhanced the expression of IgA by accelerating the expression of IL-6 that is probably combined with IL-10. The differing effects of the varied molecular weights of fucoidan may be due to the difference in the efficiency of absorption. This is a novel study on the potential preventive effects of SC-FUC on intestinal mucositis that may be related to the efficiency of its absorption during digestion. Sea cucumber fucoidan (SC-FUC) may be used as a potential food supplement to prevent chemotherapeutic mucositis.

Inhibitory effect of fucosylated chondroitin sulfate from the sea cucumber Acaudina molpadioides on adipogenesis is dependent on Wnt/β-catenin pathway.[Pubmed: 24982018]

The fucosylated chondroitin sulfate was isolated from the sea cucumber Acaudina molpadioides (Am-CHS) and its effect on the adipogenesis was investigated in vitro. Results showed that Am-CHS exhibited a marked anti-adipogenic effect. The TG contents of cells treated with Am-CHS from the early stage, mid stage and later stage were decreased by 31.76%, 19.76% and 13.85%, respectively. Wnt/β-catenin pathway acts as a negative regulator of adipogenesis. It is showed that Am-CHS enhanced the expression of the Wnt/β-catenin related factors, namely Wnt10b, β-catenin, Fz and LRP, causing more cytoplasmic β-catenin translocated into the nuclear to inhibit the expression of PPARγ and C/EBPα. SREBP-1c promotes the adipocyte differentiation by enhancing the activity of PPARγ. Reverse transcriptase-polymerase chain reaction assay and western blotting results revealed that the expressions of SREBP-1c and its transcriptional product FAS were inhibited by Am-CHS. Further study showed that Am-CHS also suppressed the PPARγ and C/EBPα expression. These results indicate that the anti-adipogenic activity of Am-CHS may exhibited by activating the Wnt/β-catenin pathway and down-regulating the SREBP-1c expression. To further verify this conclusion, in vivo experiments were performed. Results revealed that Am-CHS reduced the body adipose rate compared to high-fat-high sucrose diet (HFSD)-fed mice. Western blotting results showed that Am-CHS increased the expression of β-catenin, a negative regulator in adipogenesis, and decreased that of SREBP-1c, PPARγ and C/EBPα, the positive regulators of adipogenesis in the adipose tissue compared to the HFSD-fed group. These results further confirmed the anti-adipogenic activity of Am-CHS.

Fucoidan from the sea cucumber Acaudina molpadioides exhibits anti-adipogenic activity by modulating the Wnt/β-catenin pathway and down-regulating the SREBP-1c expression.[Pubmed: 24847504]

A novel fucoidan, which consists of a 1 → 3-linked tetrafucose repeating unit that is distinctive in its sulphation pattern, was isolated from the sea cucumber Acaudina molpadioides. In the present study, we examined the anti-adipogenic effect of the fucoidan from Acaudina molpadioides (Am-FUC) in vitro and in vivo. Results showed that Am-FUC exhibited an inhibitory effect on the proliferation and differentiation of 3T3-L1 cells. Am-FUC suppressed the differentiation of 3T3-L1 cells, decreasing the content of intracellular triglyceride by 34.07% at the concentration of 200 μg ml(-1). In vivo experiments showed that the subcutaneous, perirenal and epididymal fat content of Am-FUC-treated mice were significantly reduced compared to the HFFD-fed mice. A reverse transcriptase-polymerase chain reaction assay revealed that Am-FUC significantly increased the mRNA expressions of Wnt/β-catenin pathway related factors, namely, Wnt10b, β-catenin, Fz and LRP5, and decreased that of the key transcriptional factors, such as SREBP-1c, PPARγ and C/EBPα. β-Catenin acts as an anti-adipogenic factor to inhibit the expression of PPARγ and C/EBPα, while SREBP-1c can promote the adipocyte differentiation by enhancing the activity of PPARγ. Western blotting results showed that Am-FUC significantly increased the protein level of the total β-catenin and nuclear β-catenin and suppressed that of the SREBP-1c. Am-FUC also significantly inhibited the mRNA expressions of the lipid synthesis related genes such as FAS and GPAT, while had no effect on that of the lipolysis related genes such as HSL and ATGL. These findings suggest that Am-FUC possesses marked anti-adipogenic activity by modulating the Wnt/β-catenin pathway and down-regulating the expression of SREBP-1c.

Fucosylated chondroitin sulfate from Acaudina molpadioides improves hyperglycemia via activation of PKB/GLUT4 signaling in skeletal muscle of insulin resistant mice.[Pubmed: 24061149]

In this study, we investigated the improvement of fucosylated chondroitin sulfate (CHS) from the cucumber Acaudina molpadioides on hyperglycemia in skeletal muscle of insulin resistant mice. CHS, rosiglitazone (RSG), and their combinations were supplemented to high-fat high-sucrose diet (HFSD)-fed C57BL/6J mice for 19 weeks. The results showed that CHS treatment remarkably decreased blood glucose level and insulin resistance. The glucose metabolism-related genes expressions at the transcriptional level were apparently increased in skeletal muscle. Although the total protein expressions of IR-β, IRS-1, PI3K, PKB and GLUT4 in skeletal muscle were not affected, insulin-stimulated GLUT4 translocation and phosphorylation of Tyr-IR-β, Tyr612-IRS-1, p85-PI3K, Ser473-PKB, and Thr308-PKB were significantly increased by CHS supplement. Additionally, combination of CHS and RSG produced synergistic effects on anti-hyperglycemia. These results indicate that CHS can alleviate hyperglycemia via activation of the PKB/GLUT4 signaling pathway in skeletal muscle of insulin resistant mice.

Structural study of fucoidan from sea cucumber Acaudina molpadioides: a fucoidan containing novel tetrafucose repeating unit.[Pubmed: 24001831]

Structure of fucoidan from sea cucumber Acaudina molpadioides (Am-FUC) was investigated in this study. Low molecular weight polysaccharide of Am-FUC (Am-LMW) was prepared by enzymatic degradation and assayed by nuclear magnetic resonance. According to the structure of Am-LMW, and referring to previously reported information of Am-FUC oligosaccharides, the structure of Am-FUC was elucidated as [→3-α-l-Fucp-1→3-α-l-Fucp2,4(OSO3(-))-1→3-α-l-Fucp-1→3-α-l-Fucp2(OSO3(-))-1→]n. Compared to other investigated fucoidans, which also consist of tetrafucose repeating units with 1→3-linkages, Am-FUC contains a novel repeating unit distinctive in sulphation pattern.