EPA and DHA Alleviated Chronic Dextran Sulfate Sodium Exposure-Induced Depressive-like Behaviors in Mice and Potential Mechanisms Involved.

Patients with ulcerative colitis (UC) have higher rates of depression. However, the mechanism of depression development remains unclear. The improvements of EPA and DHA on dextran sulfate sodium (DSS)-induced UC have been verified. Therefore, the present study mainly focused on the effects of EPA and DHA on UC-induced depression in C57BL/6 mice and the possible mechanisms involved. A forced swimming test and tail suspension experiment showed that EPA and DHA significantly improved DSS-induced depressive-like behavior. Further analysis demonstrated that EPA and DHA could significantly suppress the inflammation response of the gut and brain by regulating the NLRP3/ASC signal pathway. Moreover, intestine and brain barriers were maintained by enhancing ZO-1 and occludin expression. In addition, EPA and DHA also increased the serotonin (5-HT) concentration and synaptic proteins. Interestingly, EPA and DHA treatments increased the proportion of dominant bacteria, alpha diversity, and beta diversity. In conclusion, oral administration of EPA and DHA alleviated UC-induced depressive-like behavior in mice by modulating the inflammation, maintaining the mucosal and brain barriers, suppressing neuronal damage and reverting microbiota changes.

Orally administered selenium-containing α-D-1,6-glucan and α-D-1,6-glucan relief early cognitive deficit in APP/PS1 mice.

Alzheimer's disease (AD) is a complex, progressive and deadly disorder that exhibits various typical pathological characteristics. Till now no effective treatment has been found that can prevent or reverse AD. Here, the effects of 2 months of treatment with α-D-1,6-glucan (CPA) and selenium-containing α-D-1,6-glucan (Se-CPA) on early cognitive dysfunction and neuropathology were explored in the 3-month-old APP/PS1 transgenic mouse. The results of the Morris water maze and open-field test revealed that Se-CPA exerted more significant effects than CPA in improving cognitive function and depressive-like behavior by attenuating the oxidative stress, decreasing serum LPS level, downregulating the inflammation of astrocytes and microglia through inhibiting the activation of NLRP3 inflammasome, mitigating neuronal cells loss and improving synaptic plasticity. Moreover, Se-CPA exerted beneficial effects on reshaping gut microbiome by increasing the microbial α-diversity, enhancing the proportion of beneficial bacteria such as Akkermansia muciniphila and promoting the SCFAs concentration. These findings provide evidence that Se-CPA might be a potentially viable compound for AD prevention.

Long-Term Krill Oil Administration Alleviated Early Mild Cognitive Impairment in APP/PS1 Mice.

SCOPE: Alzheimer's disease is an age-dependent neurodegenerative disorder. Mounting studies focus on the improvement of advanced cognitive impairment by dietary nutrients. Krill oil (KO), a rich source of DHA/EPA and astaxanthin, is effective in improving cognitive function. The study mainly investigates the protective effects of long-term KO administration on early cognitive impairment. METHODS AND RESULTS: Results show that 2 months KO administration (50 and 100 mg kg-1 BW) can dramatically promote learning and memory abilities. Mechanism studies demonstrate that KO reduces amyloid ß concentration by regulating the amyloidogenic pathway, inhibits neuro-inflammation via regulating TLR4-NLRP3 signaling pathway, and prevents neuron injure. KO supplementation also enhances gut barrier integrity, reduces serum lipopolysaccharide leakage, and alters the gut microbiota by reducing Helicobacteraceae, Lactobacillaceae proportion, increasing Dubosiella and Akkermansia relative abundance. Particularly, a significant increase of isovaleric acid, propionic acid, and acetic acid levels is observed after KO supplementation. Correlation analysis shows that short-chain fatty acids (SCFAs), gut microbiota, and cognitive function are strongly correlated. CONCLUSIONS: The results reveal that KO relieves early mild cognitive impairment possibly for its role in mediating the gut microbiome-SCFAs-brain axis. Thus, KO may provide potential intervention strategies to prevent cognitive impairment in the early stages through the microbiota-gut-brain axis.

DHA and EPA Alleviate Epileptic Depression in PTZ-Treated Young Mice Model by Inhibiting Neuroinflammation through Regulating Microglial M2 Polarization and Improving Mitochondrial Metabolism.

Depression is the most common complication of childhood epilepsy, leading to a poor prognosis for seizure control and poor quality of life. However, the molecular mechanisms underlying epileptic depression have not been completely elucidated. Increasing evidence suggests that oxidative stress and neuroinflammation are major contributors to depression. The positive effects of dietary supplementation with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on depression have been previously reported. However, knowledge regarding the effects of EPA and DHA in managing depressive symptoms in pediatric patients with epilepsy is limited. Therefore, this study aims to investigate the effects of EPA and DHA on epileptic depression in a pentylenetetrazole (PTZ)-treated young mouse model. Three-week-old mice were fed a DHA- or EPA-enriched diet for 21 days and treated with PTZ (35 mg/kg, i.p.) every other day for a total of 10 times. EPA was more effective than DHA at alleviating PTZ-induced depressive symptoms. Pathological results revealed that DHA and EPA significantly improved neuronal degeneration in the hippocampus. Analysis of the mechanism revealed that DHA and EPA mitigated PTZ-induced myelin damage by increasing the protein levels of CNPase, Olig2, and MBP. Furthermore, both DHA and EPA reduced neuroinflammation by promoting microglial M2 polarization and suppressing the LCN2-NLRP3 inflammasome pathway. Notably, EPA polarized microglia towards the M2 phenotype. In addition, DHA and EPA decreased oxidative stress by inhibiting NOX2 and enhancing mitochondrial metabolism through the increased expression of mitochondrial respiratory chain complex I-V proteins. These findings suggest that DHA and EPA can be used as effective interventions to improve depression in children with epilepsy, with EPA being a particularly favorable option.

Saccharina japonica Ethanol Extract Ameliorates Dextran Sulfate Sodium-Induced Colitis via Reshaping Intestinal Microenvironment and Alleviating Inflammatory Response.

Saccharina japonica belongs to brown macro-alga with various potential health benefits; its antioxidant and anti-inflammatory activities indicate the potential to improve inflammatory bowel diseases. Here, the potential anti-colitis effect of Saccharina japonica extract (SJE) was evaluated on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in C57B/L6 mice. The mice were treated with mesalazine (MES) and various doses of SJE by gavage for 14 days. Results showed that both MES and SJE treatment decreased the disease activity index scores, relieving the short colon. SJE increased the occludin and zonula occludens-1 levels, and the beneficial effects were better than MES. MES and SJE exerted similar effects in decreasing inflammatory cytokines and oxidative stress. Moreover, SJE reshaped the intestinal microbiota by increasing α-diversity and reducing plenty of harmful bacteria. Dietary SJE was significant to relieving the reduction in short-chain fatty acids. The results revealed the protective effect of SJE on colitis and potential mechanisms, which is important for the rational use of SJE in UC prevention.

Effects of methylglyoxal on shrimp tropomyosin structure and allergenicity during thermal processing.

This study aimed to analyze the effect of methylglyoxal (MGO) on the structure and allergenicity of shrimp tropomyosin (TM) during thermal processing. The structural changes were determined by SDS-PAGE, intrinsic fluorescence, circular dichroism, and HPLC-MS/MS. The allergenicity was evaluated by in vitro and in vivo experiments. MGO could cause conformational structural changes in TM during thermal processing. Moreover, the Lys, Arg, Asp, and Gln residues of TM were modified by MGO, which could destroy and/or mask TM epitopes. In addition, TM-MGO samples could lead to lower mediators and cytokines released from RBL-2H3 cells. In vivo, TM-MGO caused a significant reduction in antibodies, histamine, and mast cell protease 1 levels in sera. These results indicate that MGO can modify the allergic epitopes and reduce the allergenicity of shrimp TM during thermal processing. The study will help to understand the changes in the allergenic properties of shrimp products during thermal processing.

α-D-1,6-glucan from Castanea mollissima Blume alleviates dextran sulfate sodium-induced colitis in vivo.

A homogenous α-D-1,6-glucan (CPA) was extracted from Castanea mollissima Blume. The effect of CPA on ameliorating dextran sulfate sodium induced colitis was investigated. CPA repressed TNF-α and IL-1ß level in LPS stimulated RAW264.7 cells. After the intragastric administration of CPA (200 or 400 mg/kg/day), the colon length and body weights of mice with colitis increased and the disease activity index reduced. CPA alleviated colon tissue damage by elevating ZO-1 and occludin protein levels and regulating TNF-α and IL-1ß by inhibiting the protein expression of NLPR3 and NF-κB p65. The abundance of Bacteroidetes and Firmicutes was altered and short-chain fatty acid (SCFA) levels, especially propionic, butyric, and isovaleric acids increased significantly. These results indicated that CPA could alleviate colitis by protecting mucosal barriers, reducing inflammation, and regulating intestinal microbiota and SCFA levels. Thus, CPA can be developed as a functional food for the prevention and treatment of colitis.

Folate ameliorates homocysteine-induced osteoblast dysfunction by reducing endoplasmic reticulum stress-activated PERK/ATF-4/CHOP pathway in MC3T3-E1 cells.

INTRODUCTION: Homocysteine (Hcy) is considered a newly identified risk factor for osteoporosis. Nevertheless, the underlying mechanism of folate (FA), a key factor in the metabolism of Hcy, in protection against osteoblast dysfunction remains unclear. The purpose of this study was to investigate the mechanism by which FA attenuates Hcy-induced osteoblast damage. MATERIALS AND METHODS: The Hcy-induced MC3T3-E1 cells were treated with different concentrations of FA. Cell morphology, cell density, cell proliferation ability, alkaline phosphatase (ALP) activity and mineralization capacity were observed and determined; the gene expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX) and ERS-associated factors, including glucose-regulated protein 78 (GRP-78), activating transcription factor 4 (ATF-4) and growth arrest and DNA damage inducible gene 153 (CHOP/GADD153), were assessed by RT-PCR; and protein levels of GRP-78 and ATF-4 were analyzed by western blotting. RESULTS: Hcy suppressed the proliferation, differentiation and mineralization ability of MC3T3-E1 cells in a concentration-dependent manner and activated the ERS signaling pathway. After intervention with different concentrations of FA, the cell viability and density, ALP activity, number of mineralized nodules, calcium content and Bcl-2 gene expression were all significantly increased, whereas the gene expression of GRP-78, CHOP/GADD153, ATF-4 and Bax was markedly downregulated, and protein levels of GRP-78 and ATF-4 were also markedly decreased. CONCLUSION: The adverse effects of Hcy on osteoblast differentiation are dose dependent. FA not only protects against osteoblasts apoptosis but also has a direct osteogenic effect on Hcy-induced osteoblasts, which could be partially mediated by inhibition of the PERK-activated ERS pathway.

Orally administered melanin from Sepiapharaonis ink ameliorates depression-anxiety-like behaviors in DSS-induced colitis by mediating inflammation pathway and regulating apoptosis.

The effects of intestinal inflammation on the brain and behavior have received a lot of attention. Melanin (MSI) from Sepiapharaonis ink as an emerging functional food, it exhibited a significant protective effect on dextran sulfate sodium (DSS) induced colitis in previous study. In present study, C57BL/6J mice were free to drink 2.5% DSS solution to establish the colitis model. During the DSS treatment, mice were orally administrated with MSI once per day (75, 150, and 300 mg/kg, respectively). The results showed that MSI treatment ameliorated the depression and anxiety symptoms of colitis mice. Further mechanism studies indicated that MSI alleviated inflammatory response by adjusting cytokines TNF-α, IL-1ß, IFN-γ, and IL-10, and proteins NLRP3/ASC/caspase-1 inflammasome), inhibited the activation of microglia, restored brain synaptic density, reduced oxidative stress (SOD, MDA) and regulated apoptosis (tunel staining, caspase-3). MSI could modulate depression-anxiety states by targeting inflammation, nerve tissue, oxidative stress and apoptosis. MSI administration could serve as an emerging blue food and nutrition strategy for the prevention of digestive tract inflammation and behavioral disorders.

Ink melanin from Sepiapharaonis ameliorates colitis in mice via reducing oxidative stress, andprotecting the intestinal mucosal barrier.

Melanin is the major component from Sepiapharaonis ink (MSI), and its anti-inflammatory and antioxidant activities indicate the potential for improvement of inflammatory bowel diseases. The study aimed to investigate how orally-administered MSI on alleviating the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and the potential mechanisms. We found that MSI significantly improved DSS-induced weight loss, colon shortening, hematochezia, DAI score, histopathology, and antioxidant indices (SOD and MDA). Further analysis demonstrated that MSI could significantly down-regulate the expression of pro-inflammatory cytokines (TNF-α, IL-1ß and IFN-γ) and up-regulate the concentration of anti-inflammatory cytokine IL-10 by regulating TLR4/NF-κB and NLRP3/ASC/Caspase-1 signal pathway. Moreover, tight junction proteins in melanin groups were also maintained by ZO-1 and occludin expressions. In addition, MSI also regulated cellular apoptosis by reducing the expression of pro-apoptosis protein Caspase-3. Interestingly, MSI treatments increased the proportion of dominant bacteria (such as Bacteroidetes and Clostridium) and the abundance of community (alpha diversity, ß-diversity, etc.), which significantly balanced microbiota in a dose-dependent manner. In conclusion, oral administration of MSI alleviated DSS-induced colitis by modulating inflammatory cytokines and oxidation stress, maintaining the mucosal barrier, and reverting microbiota changes.

Supplementary selenium in the form of selenylation α-D-1,6-glucan ameliorates dextran sulfate sodium induced colitis in vivo.

The deficiency of selenium has been found in clinical IBD patients and supplementation selenium is recognized as beneficial for colitis treatment. In this study, an organic selenium compound-selenylation α-D-1,6-glucan (sCPA) was prepared, and the effect of sCPA on DSS induced colitis mice was investigated. The results suggested that sCPA prevented the weight loss, colon length shortening, and stool loose of colitis mice. It protected colon mucosal barrier by promoting tight junction protein ZO-1 and Occludin expression. Moreover, sCPA reduced oxidative stress via regulating SOD and MDA levels, and decreased the contents of inflammatory proteins NF-κB and NLRP3 and adjusted TNF-α, IFN-γ, IL-1ß, and IL-10 inflammatory cytokines. Furthermore, sCPA repaired intestinal microbiota composition especially Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria that altered by DSS in colitis mice. Meanwhile, SCFAs produced by gut microbiota were restored by sCPA close to the level in the normal group. In conclusion, these findings indicated that the sCPA might be a potential dietary selenium supplementation for the prevention and treatment of colitis.

Vitamin D deficiency in diabetes exacerbates longitudinal risk for atherosclerotic cardiovascular disease in Lanzhou, China.

BACKGROUND AND OBJECTIVES: Vitamin D deficiency has been considered a risk factor for atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to investigate the correlation between serum 25(OH)D concentration and the risk of ASCVD in Chinese, especially in Type 2 diabetes mellitus (T2DM) patients. METHODS AND STUDY DESIGN: Based on the "REACTION" study conducted in 2011, some 9,014 Lanzhou residents aged 40-75 years were followed from 2014 to 2016. A total of 7,061 with complete data were analyzed. Baseline population was classified into four groups based on 25(OH)D quartiles. Cox proportional hazard models were used to estimate relations between 25(OH)D concentration and ASCVD. RESULTS: The prevalence of vitamin D deficiency [25(OH)D <20 ng/mL] was 75.1%. Followed-up for 3.3 years, those with the lowest of 25(OH)D concentration had higher rates of ASCVD (HR: 1.748, 95% CI: 1.149-2.660, p<0.01). A 10 ng/mL increase in baseline serum 25(OH)D was accompanied by a 24 % decrease in ASCVD risk (HR: 0.760, 95% CI: 0.590-0.980, p<0.05). For 25(OH)D and ASCVD risk with glycaemic status, low 25(OH)D plus T2DM was highly associated with ASCVD (HR: 2.296, 95% CI: 1.246-4.232, p<0.01). With diabetes, ASCVD risk decreased by 36% when serum 25(OH)D increased by 10 ng/mL (HR: 0.644, 95% CI: 0.440-0.941, p<0.05). CONCLUSIONS: Serum 25(OH)D is independently and inversely associated with the risk of ASCVD in Lanzhou Chinese, especially those with T2DM. Maintaining sufficient levels of vitamin D may be an effective measure in ASCVD prevention.

Orally Administered DHA-Enriched Phospholipids and DHA-Enriched Triglyceride Relieve Oxidative Stress, Improve Intestinal Barrier, Modulate Inflammatory Cytokine and Gut Microbiota, and Meliorate Inflammatory Responses in the Brain in Dextran Sodium Sulfate Induced Colitis in Mice.

SCOPE: Studies based on DHA/EPA supplementation in animal models of inflammatory bowel disease (IBD) reveal controversial results. It is speculated that different forms of DHA may explain the controversial results. Therefore, the effects of DHA-enriched phospholipids (DHA-PL) and DHA-enriched triglyceride (DHA-TG) on IBD are compared. METHODS AND RESULTS: Male C57BL6/J mice are given DHA-PL and DHA-TG for 14 consecutive days, and receive ad libitum a 3.0% dextran sodium sulfate solution on the eighth day to establish IBD model. The results show that both DHA-PL and DHA-TG can reverse the colitis pathological process by decreasing the disease activity indexes (DAI), raising the colon length, suppressing the intestinal permeability, suppressing the oxidative stress, down-regulating pro-inflammatory factors, up-regulating anti-inflammatory factor in colon tissues. DHA-PL and DHA-TG also regulate the composition of gut microbiota via decreasing of the abundance Bacteroidetes and Firmicutes, and DHA-TG increases the abundance of Odoribacter. Importantly, DHA-PL and DHA-TG obviously attenuate the activation of microglia. CONCLUSIONS: DHA-PL shows outstanding advantages in regulating oxidative stress, inflammatory responses, and intestinal barrier permeability. The current research indicates that the existence of DHA affects the improvement, DHA in phospholipid form could be a more effective choice for nutritional intervention to prevent and treat colitis.

Saccharina japonica Ethanol Extract Ameliorates Depression/Anxiety-Like Behavior by Inhibiting Inflammation, Oxidative Stress, and Apoptosis in Dextran Sodium Sulfate Induced Ulcerative Colitis Mice.

Saccharina japonica is a common marine vegetable in East Asian markets and has a variety of health benefits. This study was focused on the anti-depressant/anxiety effects of Saccharina japonica ethanol extract (SJE) on dextran sodium sulfate (DSS)-induced mice and its potential mechanism in their brain. Male C57BL/6 mice were treated with mesalazine and various doses of SJE (1, 2, and 4 g/kg body weight) for 2 weeks, followed by DSS treatment at the second week. The DSS-induced mice showed depression/anxiety-like behavior, which included shorter path length in the open field test and longer immobility time in the tail suspension test. L-SJE alleviated the depression-like behaviors. In the DSS-induced mice, reduced synaptic plasticity activated microglia, increased proinflammatory cytokines, decreased anti-inflammatory cytokine, and increased expression levels of Toll-like receptors-4, nuclear factor kappa-B, NOD-like receptors 3, apoptosis-associated speck-like protein, and Caspase-1 were observed, most of which were alleviated by SJE treatment. Furthermore, all the SJE groups could significantly enhance superoxide dismutase activity, while the L-SJE treatment decreased the contents of malondialdehyde, and the H-SJE treatment inhibited apoptosis. All these results showed that the SJE might serve as a nutritional agent for protecting the brain in ulcerative colitis mice.

Dorsolateral Striatal proBDNF Improves Reversal Learning by Enhancing Coordination of Neural Activity in Rats.

Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. The dorsolateral striatum (DLS) is part of corticostriatal circuits that is involved in flexible behavior. Pro-brain-derived neurotrophic factor (proBDNF) can enhance fear memory extinction and weaken synaptic transmission, which may enable flexible adaptations. However, the role of proBDNF in cognitive flexibility is unclear. Here, through infusion of cleavage-resistant proBDNF or its antibody into the DLS of rats, we sought evidence for the influences by employing behavioral tests, immunoblotting, immunocytochemistry, and electrophysiological recoding. Infusion of proBDNF significantly facilitated reversal learning while inhibiting DLS proBDNF by anti-proBDNF antibody impaired the behavioral performance. Furthermore, elevation of DLS proBDNF facilitated neural correlate with reversal performance while blocking proBDNF expression decayed the spike-field coupling during the correct turning. Reversal learning induced increases in endogenous neuronal proBDNF, with a strong correlation between DLS and infralimbic cortex (IL), but not prelimbic cortex (PL) or sensory-motor cortex (SM). Importantly, blockade of IL proBDNF disrupted the DLS-mediated reversal learning enhancement, implying the involvement of both IL and DLS regions in reversal habitual behavior. Taken together, our findings provide first evidence for the essential role of the DLS proBDNF in cognitive flexibility and suggest that proBDNF-mediated neural function could be the mechanism.

EPA-enriched ethanolamine plasmalogen and EPA-enriched phosphatidylethanolamine enhance BDNF/TrkB/CREB signaling and inhibit neuronal apoptosis in vitro and in vivo.

Our previous study showed that EPA-enriched ethanolamine plasmalogen (EPA-pPE) exerted more significant effects than EPA-enriched phosphatidylethanolamine (EPA-PE) in improving learning and memory deficit. However, the results of the mechanism study were not consistent with the improved cognitive function, which suggested that other signaling pathways might be involved. In the present study, primary cultured hippocampal neurons and cognitive deficiency rats were used to compare the effects of EPA-pPE and EPA-PE on brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element-binding protein (CREB) signaling and neuronal apoptosis. The in vitro experiment showed that both EPA-pPE and EPA-PE could relieve cell death and improve the cellular morphology of neurons via upregulating anti-apoptotic proteins and downregulating pro-apoptotic proteins. The in vivo experiment showed that EPA-pPE exerted more significant effects than EPA-PE in improving the number of neuronal Nissl bodies, increasing the branching of dendrites and dendritic spine density in cortical neurons, as well as improving the expression of synaptic vesicle-related proteins synaptophysin (SYN) and PSD95 via BDNF/TrkB/CREB signaling. These results indicated that EPA-pPE exerted neuroprotection at least partly through inhibiting neuronal apoptosis and enhancing the BDNF/TrkB/CREB pathway, which suggests that EPA-enriched plasmalogen can be explored as a potential therapeutic agent in long-term Alzheimer's disease therapy.

Efficient extraction of chitin from shrimp waste by mutagenized strain fermentation using atmospheric and room-temperature plasma.

Chitin extraction from shrimp waste by protease-producing microorganisms was a positive and simple method. To improve the protease activity of microorganism used for the extraction of chitin, atmospheric and room temperature plasma technology was adopted to induce mutations in Exiguobacterium profundum, a protease-producing bacterium, which was isolated from traditional fermented shrimp paste. After several rounds of screening, the mutant numbered 10017 was screened. The hereditary properties of the mutant were found to be stable after a series of passages. This strain was subsequently used in the deproteinization process, which could remove 91.48% ± 2.60% protein, and the chitin recovery was 70.18 ± 2.68%. Fourier transform infrared spectrometry, X-ray diffraction, and scanning electron microscopy was adopted to compare the characteristics of the chitin extracted from mutagenized and wild-type strain fermentation. The crystallinity indices were 80.72% and 82.46%, and the degrees of deacetylation were 15.78% and 27.84%. These results indicated that the deproteinization by mutagenized strain fermentation might be applied to the production of chitin. Thus, the present study provides an appropriate strategy to develop an efficient method to improve protease activity in microbial fermentation.

Cerebrosides from Sea Cucumber Improved Aß1-42 -Induced Cognitive Deficiency in a Rat Model of Alzheimer's Disease.

SCOPE: Cerebrosides are a class of neutral glycosphingolipids, which are widely found to be present in brain tissue. In this study, the protective effect of sea cucumber cerebrosides (Cer) against ß-amyloid (Aß)-induced cognitive impairment is investigated. METHODS AND RESULTS: Male SD rats receive a ventricle injection Aß1-42 peptide to establish an Alzheimer's disease model. Then, the protective effects of Cer against Aß1-42 -induced cognitive impairment by gavage and feed addition are evaluated. The Morris water maze test results show that oral administration of Cer can significantly ameliorate Aß1-42 -induced cognitive deficiency at both high dose (200 mg per kg·per day) and low dose (40 mg per kg·per day) for 27 days. Dietary supplement of Cer by feed addition also exhibits the amelioration on the impaired cognitive function. Further findings indicate that Cer ameliorates Aß1-42 -induced neuronal damage and suppresses the induced apoptosis by decreasing the level of Bax/Bcl-2. Additionally, Cer enhances the expressions of PSD-95 and synaptophysin by activating BDNF/TrkB/CREB signaling pathway, thereby ameliorating Aß1-42 -induced synaptic dysfunction. Furthermore, Cer attenuates Aß1-42 -induced tau hyperphosphorylation by activating the PI3K/Akt/GSK3ß signaling pathway. CONCLUSION: Sea cucumber cerebrosides possess neuroprotective effects against Aß1-42 -triggered cognitive deficits, which may be a potential nutritional preventive strategy for neurodegenerative diseases.

Synergistic effect of eicosapentaenoic acid-enriched phospholipids and sea cucumber saponin on orotic acid-induced non-alcoholic fatty liver disease in rats.

Non-alcoholic fatty liver disease (NAFLD) is becoming an increasingly prevalent chronic liver disease all over the world. The present study was undertaken to explore the synergistic effects of sea cucumber saponins (SCS) and eicosapentaenoic acid-enriched phospholipids (EPA-PL) at ratios of 0.5 : 0.5 and 1 : 1 on NAFLD and demonstrate possible protective mechanisms. It was found that the combination of EPA-PL and SCS at half dose exhibited better effects than EPA-PL or SCS alone and the combination of EPA-PL and SCS at full dose in alleviating orotic acid (OA)-induced symptoms including growth parameters, serum parameters and liver function. Further evaluation of the mechanism illustrated that EPA-PL and SCS combination at the ratio of 0.5 : 0.5 could markedly reduce the mRNA expressions of fatty acid synthase, acetyl-CoA carboxylase, glucose-6-phosphate dehydrogenase and malic enzyme genes and significantly increase expression of genes relevant to fatty acid ß-oxidation including peroxisome proliferator-activated receptor and its target genes (CPT1, CPT2 and ACOX1), suggesting that the protection of the EPA-PL and SCS combination at the ratio of 0.5 : 0.5 against OA-induced NAFLD might be mainly via lipogenesis inhibition and ß-oxidation enhancement in the liver. The synergistic effects of EPA-PL and SCS make it possible to reduce the doses of EPA-PL or SCS to avoid side effects, which is of value for the development of dietary supplements or functional foods for preventing or treating NAFLD.

Mechanisms of DHA-enriched phospholipids in improving cognitive deficits in aged SAMP8 mice with high-fat diet.

Recent studies have shown that a high-fat diet (HFD) is involved in both metabolic dysfunction and cognitive deficiency and that docosahexaenoic-acid-enriched phospholipids (DHA-PLs) have beneficial effects on obesity and cognitive impairment. However, there are only a few studies comparing differences between DHA-PC and DHA-PS in HFD-induced Alzheimer's disease (AD) models. After 8 weeks feeding with HFD, 10-month-old SAMP8 mice were fed with 1% (w/w) DHA-PC or 1% DHA-PS (biosynthesized from DHA-PC) for 8 weeks; we then tested the behavioral performances in the Barnes maze test and Morris maze test. The changes of the generation and accumulation of Aß, oxidative stress, apoptosis, neuroinflammation and neurotrophic factors were also measured. The results indicated that both DHA-PC and DHA-PS significantly improved the metabolic disorders and cognitive deficits. Both DHA-PC and DHA-PS could ameliorate oxidative stress, and DHA-PS presented more notable benefits than DHA-PC on Aß pathology, mitochondrial damage, neuroinflammation and neurotrophic factors; DHA-PS was for the first time found to increase the production of insoluble Aß (less pathogenic) in this AD model. These data suggest that DHA-PLs can significantly improve cognitive deficiency, and the molecular mechanisms for this closely relate to the phospholipid polar groups.