Shiwei Hu

Fucoidan from sea cucumber may improve hepatic inflammatory response and insulin resistance in mice

Nutrition excess-induced inflammation positively contributed to insulin resistance. Fucoidan from sea cucumber can increase glucose translocation in skeletal muscle. However, its effects on inflammation-associated insulin resistance are not understood. We investigated fucoidan from Isostichopus badionotus (Ib-FUC)-alleviated inflammatory response and signaling as well as -improved insulin resistance in the liver of obesity mice. The results showed that Ib-FUC reduced body weight and glucose levels, increased insulin sensitivity, and inhibited serum lipid concentrations. Meanwhile, Hepatic glycogen synthesis was promoted by Ib-FUC via activation of the PI3K/PKB/GSK-3β signaling and regulation of glucose metabolism-related enzymatic activities. Ib-FUC regulated serum inflammatory cytokines and their mRNA expression in the liver. Ib-FUC-induced inactivation of the JNK and IKKβ/NFκB pathways was involved in the activation of insulin signal cascade and inflammatory factor production. These findings suggested that Ib-FUC supplementary-induced alleviation of inflammatory response could be a mechanism responsible for its beneficial effects against hepatic insulin resistance.

Fucosylated Chondroitin Sulfate from Sea Cucumber Improves Insulin Sensitivity via Activation of PI3K/PKB Pathway

This study was to investigate the effects of fucosylated chondroitin sulfate (CHS) from sea cucumber on insulin sensitivity in skeletal muscle of type 2 diabetic mice induced by a high-fat high-sucrose diet (HFSD). CHS supplementation for 19 wk significantly improved insulin sensitivity by 20%, and reduced blood glucose and insulin levels. Western blotting assay showed that CHS significantly increased insulin-stimulated glucose transporter 4 (GLUT4) translocation to 1.7-fold, phosphorylation of phosphoinositide 3-kinase (PI3K) at p85 to 5.0-fold, protein kinase B (PKB) at Ser473 to 1.5-fold, and Thr308 to 1.6-fold in skeletal muscle. However, PI3K, PKB, and GLUT4 total proteins expression were unchangeable. In addition, qRT-PCR analysis proved that the insulin signaling was activated by CHS treatment, showing the increased mRNA expressions of glucose uptake-related key genes. It indicated that CHS improved insulin sensitivity by activation of PI3K/PKB signaling in skeletal muscle of type 2 diabetic mice. Identification of potential mechanism by which CHS increased insulin sensitivity might provide a new functional food or pharmaceutical application of sea cucumber.

Long-chain bases from sea cucumber mitigate endoplasmic reticulum stress and inflammation in obesity mice

Endoplasmic reticulum (ER) stress and inflammation can induce hyperglycemia. Long-chain bases (LCBs) from sea cucumber exhibit antihyperglycemic activities. However, their effects on ER stress and inflammation are unknown. We investigated the effects of LCBs on ER stress and inflammatory response in high-fat, fructose diet-induced obesity mice. Reactive oxygen species and free fatty acids were measured. Inflammatory cytokines in serum and their mRNA expressions in epididymal adipose tissues were investigated. Hepatic ER stress-related key genes were detected. c-Jun NH2-terminal kinase and nuclear factor κB inflammatory pathways were also evaluated in the liver. Results showed that LCBs reduced serum and hepatic reactive oxygen species and free fatty acids concentrations. LCBs decreased serum proinflammatory cytokines levels, namely interleukin (IL)-1β, tumor necrosis factor-α, IL-6, macrophage inflammatory protein 1, and c-reactive protein, and increased anti-inflammatory cytokine IL-10 concentration. The mRNA and protein expressions of these cytokines in epididymal adipose tissues were regulated by LCBs as similar to their circulatory contents. LCBs inhibited phosphorylated c-Jun NH2-terminal kinase and inhibitor κ kinase β, and nuclear factor κB nuclear translocation. LCBs also inhibited mRNA expression of ER stress markers glucose regulated protein, activating transcription factor 6, double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase, and X-box binding protein 1, and phosphorylation of eukaryotic initiation factor-α and inositol requiring enzyme 1α. These results indicate that LCBs can alleviate ER stress and inflammatory response. Nutritional supplementation with LCBs may offer an adjunctive therapy for RE stress-associated inflammation.

Long-chain bases from Cucumaria frondosa inhibit adipogenesis and regulate lipid metabolism in 3T3-L1 adipocytes

This study aims to investigate anti-adipogenic effects of long-chain bases from Cucumaria frondosa (Cf-LCBs) in vitro. Results showed that Cf-LCBs inhibited adipocyte differentiation and the expressions of CCAAT/enhancer binding proteins (C/EBPs) and peroxisome proliferators-activated receptor γ (PPARγ). Cf-LCBs increased β-catenin mRNA and nuclear translocation and increased its target genes, cyclin D1 and c-myc. Cf-LCBs enhanced fizzled and lipoprotein-receptor-related protein5/6 (LRP5/6) expressions, whereas wingless-type MMTV integration site10b (WNT10b) and glycogen syntheses kinase 3β (GSK3β) remained unchanged. Cf-LCBs also reduced adipogenesis and recovered WNT/β-catenin signaling in the cells suffering from 21H7, a β-catenin inhibitor. In addition, Cf-LCBs decreased triglyceride content and the expressions of lipogenesis genes. Cf-LCBs increased FFA levels and the expressions of lipidolytic factors. Cf-LCBs promoted the phosphorylation of adenosine-monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase. These findings indicate that Cf-LCBs inhibit adipogenesis through activation of WNT/β-catenin signaling and regulate lipid metabolism via activation of AMPK pathway.

Fucoidan from Acaudina molpadioides protects pancreatic islet against cell apoptosis via inhibition of inflammation in type 2 diabetic mice

Inflammation induces pancreatic islet cell apoptosis. Effects of fucoidan from Acaudina molpadioides (Am-FUC) on inhibition of pancreatic islet cell apoptosis and inflammation in type 2 diabetic mice were investigated. Am-FUC repaired pancreatic islet cells, decreased serum C-reactive protein (CRP), macrophage inflammatory protein 1 (MIP-1), interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) levels, and increased the IL-10 level. Am-FUC also reduced TNF-α, CRP, MIP-1, IL-1β, and IL-6 mRNA expressions, and increased IL-10 mRNA expression in epididymal adipose tissues. Am-FUC reduced Bid, Bax, cytochrome c, caspase 9, and caspase 3 mRNA expressions, and increased Bcl-2 and Bcl-xL mRNA expressions. Am-FUC down-regulated t-Bid, Bax, cytochrome c, and caspase 9 activities, cleaved caspase 3 proteins, and up-regulated Bcl-2 and Bcl-xL proteins. Thus, an Am-FUCblocked mitochondrial pathway was the suppression mechanism in pancreatic islet cell apoptosis via regulation of inflammatory cytokines providing dietary intervention in type 2 diabetes and inflammation-induced pancreatic islet apoptosis.

Fucosylated chondroitin sulfate from sea cucumber inhibited islets of langerhans apoptosis via inactivation of the mitochondrial pathway in insulin resistant mice

The effects of fucosylated chondroitin sulphate from sea cucumber (CHS) on inhibition of pancreatic islet apoptosis in high-fat high-sucrose diet (HFSD)-induced insulin resistant mice were studied for 19 weeks. CHS treatment significantly (p<0.05) decreased fasting blood glucose, insulin, and tumor necrosis factor (TNF)-α levels, and increased the serum adiponectin level, improved insulin resistance, and repaired HFSD-injured islets of langerhans, compared with controls. CHS supplementation significantly (p<0.05) inhibited pancreas cell apoptosis via reduction of cytochrome c, caspase 9, and caspase 3 mRNA expressions, cytochrome c release into the cytoplasm, and caspase 9 and cleaved-caspase 3 protein expressions, compared with controls. These effects were associated with upregulation of Bcl-2 and Bcl-xL mRNA and protein expressions, and downregulation of Bax and t-Bid mRNA and protein expressions. Combination treatments with CHS and rosiglitazone synergistically protected pancreatic islets. CHS improves insulin resistance and protects islets of langerhans from apoptosis via inactivation of the intrinsic mitochondrial pathway.

Hpyerglycemic effect of a mixture of sea cucumber and cordyceps sinensis in streptozotocin-induced diabetic rat

Sea cucumber and cordyceps sinensis are used as both food and traditional medicines in Asia. This study was carried out in order to investigate the hpyerglycemic effect of a mixture of sea cucumber (Apostichopus japonicas) and cordyceps sinensis (Cordyceps militaris) (SCC) in diabetic rat and explore the mechanism underlining such an effect. The diabetic model rat was induced with intraperitoneal injection of streptozotocin (STZ). The diabetic model rats were randomly divided into control group (0.9% NaCl), low dose group (300 mg SCC·(kg body weight)−1) and high dose group (1200 mg SCC (kg body weight)−1). Sodium chloride and SCC were intragastrically administered once a day for 35 d. Changes in fasting serum glucose and serum insulin content, oral glucose tolerance and liver and muscle glycogen content were routinely evaluated. Pancreas tissue and β-cells of islets were observed under both optical and transmission electronic microscope, respectively. The abundance of glucose metabolism-relating genes in gastrocnemius and epididymal adipose tissue was determined with either reverse transcription PCR (RT-PCR) or western blotting. Results showed that SCC significantly decreased fasting serum glucose content, improved glucose tolerance and increased serum insulin and glycogen content; repaired STZ-injured β-cells of diabetic rat, and increased the expression of phosphatidylinositol 3 kinase (PI(3)K), protein kinase B (PKB) and glucose transporter 4 (Glut4) encoding protein in both gastrocnemius and adipose tissue, and Glut4 encoding gene in peripheral tissue. Our findings demonstrated that SCC exerted an anti-hyperglycemic effect by repairing β-cells and promoting insulin-mediated signal transduction pathway in insulin-sensitive gastrocnemius and adipose tissue.

The effects of fucosylated chondroitin sulfate isolated from Isostichopus badionotus on antimetastatic activity via down-regulation of Hif-1α and Hpa

Fucosylated chondroitin sulfate (CHS) was prepared from the sea cucumber Isostichopus badionotus (Ib-CHS), and the antimetastatic effect was studied using cell adhesion, migration, invasion, chorioallntoic membrane (CAM), and reverse transcriptase-polymerase chain reaction (RT-PCR) assays. Ib-CHS remarkably suppressed proliferation of 95D cells, and inhibited adhesion, migration, and invasion of 95D cells in a dose-dependent manner. CAM assay results suggested that Ib-CHS attenuates neovascularization in the chick embryo. RT-PCR analyses revealed that Ib-CHS dramatically decreased expression of matrix metalloproteinase-2/9 (MMP-2/9), hypoxia-inducible factor (Hif-1α), heparanase (Hpa), and vascular endothelial growth factor (VEGF), and increased expression levels of the tissue inhibitors of metalloproteinase-1/2 (TIMP-1/2), important inhibitors of MMP-2/9. Ib-CHS markedly inhibited tumor growth, improved the metastatic foci occurrence rate, and down-regulated expressions of Hif-1α, Hpa, and VEGF in vivo. Ib-CHS exerted antimetastatic activities in vitro and in vivo.