Publications by authors named "Chang-Hu Xue"

73 Publications

Dietary n-3 PUFA Deficiency Increases Vulnerability to Scopolamine-Induced Cognitive Impairment in Male C57BL/6 Mice.

J Nutr 2021 May 12. Epub 2021 May 12.

College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong, China.

Background: DHA (22:6n-3), a long-chain n-3 PUFA, is essential for normal brain development and function. Our previous study demonstrated that DHA significantly improves scopolamine-induced dementia. However, there are no reports on the relation between n-3 PUFA deficiency and scopolamine-induced cognitive impairment.

Objectives: The aim of this study was to evaluate whether n-3 PUFA deficiency increases vulnerability to scopolamine-induced cognitive impairment.

Methods: Male and female C57BL/6 mice were mated and fed an n-3 PUFA-adequate [containing 2.88% α-linolenic acid (ALA; 18:3n-3)] or -deficient (containing 0.09% ALA) diet for 2 consecutive generations. The corresponding second-generation male offspring were kept on the same diet as their mothers after weaning, and were randomly assigned to 2 subgroups at 7 wk of age, in which they were intraperitoneally injected with saline [fed n-3 PUFA-adequate (Con) or -deficient (Def) diet] or scopolamine [5 mg/kg body weight; fed n-3 PUFA-adequate (Sco) or -deficient (Def + Sco) diet] once per day for 7 d before killing. Behavioral performance was analyzed using the Morris Water Maze test. Fatty acid composition, protein expression, and indicators of cholinergic and oxidative stress in the brain were measured.

Results: The Def group showed lower brain DHA (-63.7%, P ≤ 0.01) and higher n-6 PUFA (+65.5%, P ≤ 0.05) concentrations than the Con group. The Def + Sco group and the Sco group showed poorer spatial learning and memory (escape latency on the sixth day: +60.3% and +36.8%; platform crossings: -43.9% and -28.2%, respectively) and more obvious cholinergic dysfunction (acetylcholine: -47.6% and -27.7%, respectively), oxidative stress (glutathione peroxidase: -64.2% and -32.5%, respectively), apoptosis [B-cell lymphoma 2 (BCL2)-associated X protein/BCL2: +230.8% and +153.8%; phosphorylated P38/P38: +232% and +130%, phosphorylated c-Jun N-terminal kinase (JNK)/JNK: +104.5% and +58.8%, respectively], neuroinflammation (IL-1β: +317.6% and +95%, respectively), and neurodevelopmental delay (brain-derived neurotrophic factor: -54.4% and -7.25%, respectively) than their corresponding saline-treated controls.

Conclusions: Dietary n-3 PUFA deficiency significantly decreases brain DHA concentrations and increases vulnerability to scopolamine-induced cognitive impairment in C57BL/6 male mice.
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http://dx.doi.org/10.1093/jn/nxab116DOI Listing
May 2021

Sterol sulfate alleviates atherosclerosis mediating hepatic cholesterol metabolism in ApoE mice.

Food Funct 2021 Jun;12(11):4887-4896

College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, Shandong, China.

Compared with terrestrial organisms, the sterols in sea cucumber exhibit a sulfate group at the C-3 position. Our previous study demonstrated that dietary sterol sulfate was superior to phytosterol in alleviating metabolic syndrome by ameliorating inflammation and mediating cholesterol metabolism in high-fat-high-fructose diet mice, which indicated its potential anti-atherosclerosis bioactivity. In the present study, administration with sea cucumber-derived sterol sulfate (SCS) significantly decreased the cholesterol level in oleic acid/palmitic acid-treated HepG2 cells, while no significant changes were observed in the triacylglycerol level. RNA-seq analysis showed that the metabolic changes were mostly attributed to the steroid biosynthesis pathway. ApoE-/- mice were used as an atherosclerosis model to further investigate the regulation of SCS on cholesterol metabolism. The results showed that SCS supplementation dramatically reduced atherosclerotic lesions by 45% and serum low-density lipoprotein cholesterol levels by 59% compared with the model group. Dietary SCS inhibited hepatic cholesterol synthesis via downregulating SREBP-2 and HMGCR. Meanwhile, SCS administration increased cholesterol uptake via enhancing the expression of Vldlr and Ldlr. Noticeably, SCS supplementation altered bile acid profiles in the liver, serum, gallbladder and feces, which might cause the activation of FXR in the liver. These findings provided new evidence about the high bioactivity of sterols with the sulfate group on atherosclerosis.
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http://dx.doi.org/10.1039/d0fo03266bDOI Listing
June 2021

A comparative study of the effects of phosphatidylserine rich in DHA and EPA on Aβ-induced Alzheimer's disease using cell models.

Food Funct 2021 May 20;12(10):4411-4423. Epub 2021 Apr 20.

College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, Shandong, China.

Alzheimer's disease (AD) is an age-dependent, irreversible neurodegenerative disease, and one of the pathological features is amyloid-β (Aβ) deposition. Previous studies have shown that phosphatidylserine (PS) enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exhibited significant effects in preventing and alleviating the progress of AD. However, no studies have focused on the differences in the preventive effects on AD between EPA-PS and DHA-PS. Here, the effects of EPA-PS and DHA-PS on Aβ production, Aβ-induced neurotoxicity and Aβ clearance have been studied. The results show that DHA-PS significantly reduced Aβ production in CHO-APP/PS1 cells compared to EPA-PS. Moreover, both EPA-PS and DHA-PS significantly protected the primary hippocampal neurons against Aβ-induced toxicity by inhibiting the mitochondrial-dependent apoptotic pathway and phosphorylation of JNK and p38. Compared to DHA-PS, EPA-PS administration significantly improved the Aβ phagocytic capacity of BV2 cells. In addition, EPA-PS and DHA-PS significantly promoted the neurite outgrowth of primary hippocampal neurons. These findings might provide dietary guidance for the prevention of AD as well as a reference for the development of related functional foods.
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http://dx.doi.org/10.1039/d1fo00286dDOI Listing
May 2021

Trimethylamine -Oxide Generation from Choline-Containing Precursors Is Closely Associated with Their Molecular Structure.

J Agric Food Chem 2021 Mar 4;69(10):2933-2935. Epub 2021 Mar 4.

College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong 266003, People's Republic of China.

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http://dx.doi.org/10.1021/acs.jafc.1c01068DOI Listing
March 2021

Dietary Supplementation with Exogenous Sea-Cucumber-Derived Ceramides and Glucosylceramides Alleviates Insulin Resistance in High-Fructose-Diet-Fed Rats by Upregulating the IRS/PI3K/Akt Signaling Pathway.

J Agric Food Chem 2021 Feb 9. Epub 2021 Feb 9.

College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong 266003, People's Republic of China.

Endogenous ceramide is considered to be associated with the progress of insulin resistance. However, the effects of dietary exogenous glucosylceramides and ceramides on insulin resistance are unclear. A model of fructose-induced male Sprague Dawley rats was used to compare the effects of sea-cucumber-derived glucosylceramides and ceramides on insulin resistance. Both glucosylceramides and ceramides significantly improved glucose tolerance, reduced the concentrations of serum glucose and glycosylated hemoglobin, and alleviated the accompanied hypertension. Ceramides significantly enhanced glycogen levels in skeletal muscle, whereas glucosylceramides significantly increased the hepatic glycogen levels. Moreover, glucosylceramides alleviated insulin resistance by inhibiting gluconeogenesis, promoting glycogen synthesis and insulin signal transduction in the liver; meanwhile, ceramides were mainly due to the promotion of glycogen synthesis and insulin signal transduction in skeletal muscle. Additionally, glucosylceramides and ceramides effectively attenuated inflammation in adipose tissue. These results indicate that glucosylceramides and ceramides have potential value in the prevention and alleviation of insulin resistance.
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http://dx.doi.org/10.1021/acs.jafc.0c06831DOI Listing
February 2021

Effects of Dietary Supplementation with EPA-enriched Phosphatidylcholine and Phosphatidylethanolamine on Glycerophospholipid Profile in Cerebral Cortex of SAMP8 Mice fed with High-fat Diet.

J Oleo Sci 2021 Feb 15;70(2):275-287. Epub 2021 Jan 15.

College of Food Science and Engineering, Ocean University of China.

The destruction of lipid homeostasis is associated with nervous system diseases such as Alzheimer's disease (AD). It has been reported that dietary EPA-enriched phosphatidylcholine (EPA-PC) and phosphatidylethanolamine (EPA-PE) could improve brain function. However, it was unclear that whether EPA-PC and EPA-PE intervention could change the lipid composition of cerebral cortex in AD mice. All the senescence-accelerated mouse-prone 8 (SAMP8) mice were fed with a high-fat diet for 8 weeks. After another 8 weeks of intervention with EPA-PC and EPA-PE (1%, w/w), the cerebral cortex lipid levels were determined by lipidomics. Results demonstrated that dietary supplementation with EPA-PE and EPA PC for 8 weeks significantly increased the amount of choline plasmalogen (pPC) and Lyso phosphatidylethanolamine (LPE) in the cerebral cortex of SAMP8 mice fed with high fat diet. Meanwhile, administration with EPA-PE and EPA-PC could significantly decrease the level of docosapentaenoic acid (DPA)-containing phosphatidylserine (PS) as well as increase the levels of arachidonic acid (AA)-containing phosphatidylethanolamine and PS in cerebral cortex. EPA-PE and EPA-PC could restore the lipid homeostasis of dementia mice to a certain degree, which might provide a potential novel therapy strategy and direction of dietary intervention in patients with cognitive impairment.
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http://dx.doi.org/10.5650/jos.ess20212DOI Listing
February 2021

The enrichment of eggs with docosahexaenoic acid and eicosapentaenoic acid through supplementation of the laying hen diet.

Food Chem 2021 Jun 29;346:128958. Epub 2020 Dec 29.

College of Food Science and Engineering, Ocean University of China, Qingdao 266003, Shandong, PR China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, Shandong Province, PR China. Electronic address:

The enrichment and transformation of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) enriched phospholipids for eggs deserve attention. The aim of the present study was to elucidate the comparative effects of DHA and EPA enriched phospholipids and triacylglycerols on egg fortification by determining the fatty acid composition of egg yolk after intervention with fish oil (15 g/kg) and krill oil (15 and 30 g/kg) for three consecutive weeks. The results indicated that laying hens could incorporate over 300 mg DHA and EPA into one egg. Greater retention efficiency of DHA and EPA in eggs was observed in fish oil supplementation compared with krill oil at equivalent dietary levels. DHA and EPA were prone to locate at the sn-2 position of phosphatidylcholine. Consequently, fish oil possessed high DHA content and conversion rate, and krill oil could raise the proportion of DHA-containing phospholipids in eggs.
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http://dx.doi.org/10.1016/j.foodchem.2020.128958DOI Listing
June 2021

Effects of dietary n-3 PUFA levels in early life on susceptibility to high-fat-diet-induced metabolic syndrome in adult mice.

J Nutr Biochem 2021 03 31;89:108578. Epub 2020 Dec 31.

College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong, China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, Shandong, China. Electronic address:

The maternal nutritional status during pregnancy and lactation was closely related to the growth and development of the fetus and infants, which had a profound impact on the health of the offspring. N-3 polyunsaturated fatty acid (PUFA) had been proved to have beneficial effects on glucolipid metabolism. However, the effects of dietary different n-3 PUFA levels for mother during pregnancy and lactation on susceptibility to high-fat-diet-induced metabolic syndrome for offspring in adulthood are still unclear. The maternal mice were fed with control, n-3 PUFA-deficient or fish oil-contained n-3 PUFA-rich diets during pregnancy and lactation, and the weaned offspring were fed with high-fat or low-fat diet for 13 weeks, then were subjected to oral glucose tolerance tests. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate the high-fat-diet-induced glucolipid metabolism disorders, including glucose intolerance, insulin resistance, obesity, and dyslipidemia, thus increased the susceptibility to metabolic syndrome of adult mice. Notably, nutritional supplementation with n-3 PUFA in early life could significantly alleviate the glucose metabolism disorders by increasing insulin sensitivity, inhibiting gluconeogenesis and promoting glycogenesis. In addition, administration with n-3 PUFA in early life remarkably reduced serum and hepatic lipid profiles by mediating the expression of genes related to lipogenesis and β-oxidation of fatty acids. Dietary n-3 PUFA-deficiency in early life increases the susceptibility to metabolic syndrome of adult offspring, and nutritional supplementation with n-3 PUFA enhances the tolerance to a high-fat diet of adult offspring.
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http://dx.doi.org/10.1016/j.jnutbio.2020.108578DOI Listing
March 2021

Comparative study on the digestion and absorption characteristics of n-3 LCPUFA-enriched phospholipids in the form of liposomes and emulsions.

Food Res Int 2020 11 10;137:109428. Epub 2020 Jun 10.

College of Food Science and Engineering, Ocean University of China, No. 5 Yushan Road, Qingdao, Shandong Province 266003, PR China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, Shandong Province, PR China. Electronic address:

Previous studies have reported that phospholipids rich in n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) in the form of liposome exhibited superior bioactivities than other formulation. However, the digestion and absorption characteristics of n-3 LCPUFA-enriched phospholipids were still unclear, restricting the molecular mechanism analysis related to their distinctive activities. The aim of the present study was to compare the digestion and absorption characteristics of DHA/EPA-PC in the forms of liposome and emulsion. The fatty acid composition and lipid species in serum, intestinal wall and content of healthy mice were determined after oral administration with DHA/EPA-PC. Results showed that the peak value of serum DHA/EPA level in the liposome group was significantly higher than that of the emulsion group (p < 0.05), although the peak in the liposome group appeared at 3 h and the peak time was 2 h in the emulsion group. Lipidomics analysis indicated that the high levels of total PL and PL-DHA could be retained in serum for a substantial period after administration of the DHA/EPA-PC liposome, which might be attributed to that the DHA/EPA-PC in the form of liposomes was hydrolyzed slower by pancreatic phospholipase A2 than the emulsion form in small intestinal content. The obtained results might provide theoretical basis for the development and utilization of marine-derived phospholipids.
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http://dx.doi.org/10.1016/j.foodres.2020.109428DOI Listing
November 2020

Sea cucumbers-derived sterol sulfate alleviates insulin resistance and inflammation in high-fat-high-fructose diet-induced obese mice.

Pharmacol Res 2020 10 8;160:105191. Epub 2020 Sep 8.

College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, Shandong, China; Laboratory of Marine Drugs & Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266237, Shandong Province, China. Electronic address:

Sea cucumbers are widely consumed in traditional medicine and food. Sea cucumbers-derived sulfated sterol exhibits a sulfate group at C-3 position, which is different from phytosterol with a hydroxyl group. However, the effect of sterol sulfate on metabolic syndrome remains unknown. The purpose of the present study is to investigate the alleviation of sterol sulfate on high-fat-high-fructose diet (HFFD)-induced insulin resistance and inflammation. After 2 weeks feeding with HFFD, male C57BL/6J mice were continuously fed with HFFD plus 0.4 % (w/w) sterol sulfate or phytosterol for 6 weeks. The OGTT was carried out at 7 weeks. At the end of the experimental period, the changes of glycogen, circulating glucose, insulin, pro-inflammatory cytokine and adiponectin were measured. H&E staining was used to observe the morphological changes in adipose tissue. Furthermore, the underlying molecular mechanisms were investigated. Dietary sterol sulfate was superior to phytosterol in reducing body weight gain, adipocyte hypertrophy, and levels of circulating glucose and insulin, as well as increasing the glycogen content of tissues. Furthermore, sterol sulfate ameliorated insulin resistance mainly due to the inhibition of gluconeogenesis, the promotion of glycogen synthesis and GLUT4 translocation by activating PI3K/Akt signaling pathway. Additionally, sterol sulfate effectively attenuated inflammation by increasing serum adiponectin and reducing pro-inflammatory cytokine release. Sterol sulfate exhibited a more significant effect than phytosterol in alleviating HFFD -induced insulin resistance and inflammation, which might be closely related to the sulfate group. The results might provide insights into the prevention and alleviation of metabolic syndrome.
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http://dx.doi.org/10.1016/j.phrs.2020.105191DOI Listing
October 2020

Docosahexaenoic acid-acylated astaxanthin ester exhibits superior performance over non-esterified astaxanthin in preventing behavioral deficits coupled with apoptosis in MPTP-induced mice with Parkinson's disease.

Food Funct 2020 Sep;11(9):8038-8050

College of Food Science and Engineering, Ocean University of China, No. 5 Yushan Road, Qingdao 266003, P. R. China. and Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, Shandong Province, P. R. China.

Non-esterified astaxanthin (AST) has been reported to exhibit protective effects from Parkinson's disease (PD). Notably, DHA-acylated astaxanthin ester (DHA-AST) is widely distributed in the seafood. However, whether DHA-AST has an effect on PD, and the differences between DHA-AST, non-esterified AST and the combination of non-esterified AST (AST) with DHA (DHA + AST) is unclear. In the present study, mice with PD, induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were employed to investigate the effects of DHA-AST, AST and DHA + AST on Parkinson's disease. The rotarod test results showed that DHA-AST significantly suppressed the PD development in MPTP-induced mice, and was better than the effects of AST and DHA + AST. Further mechanistic studies indicated that all three astaxanthin supplements could inhibit oxidative stress in the brain. It was noted that DHA-AST had the best ability to suppress the apoptosis of dopaminergic neurons via the mitochondria-mediated pathway and JNK and P38 MAPK pathway in the brain among the three treated groups. DHA-AST was superior to AST in preventing behavioral deficits coupled with apoptosis rather than oxidative stress, and might provide a valuable reference for the prevention and treatment of neurodegenerative diseases.
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http://dx.doi.org/10.1039/d0fo01176bDOI Listing
September 2020

Effect of Stored Humidity and Initial Moisture Content on the Qualities and Mycotoxin Levels of Maize Germ and Its Processing Products.

Toxins (Basel) 2020 08 20;12(9). Epub 2020 Aug 20.

College of Food Science and Engineering, Ocean University of China, No.5, Yushan Road, Qingdao, Shandong Province 266003, China.

With high fat and protein content, maize germ is easily infected with fungus and mycotoxins during its storage. The qualities and safety of germ and its processing products may be affected by the storage. However, studies on the effect of storage on quality and polluted mycotoxin level of maize germ are limited. In this study, maize germ was stored with different initial moisture contents (5.03, 9.07, 11.82 and 17.97%) or at different relative humidity (75, 85 and 95%) for 30 days. The quality indices of germ (moisture content and crude fat content) and their produced germ oils (color, acid value and peroxide value) as well as the zearalenone (ZEN) and deoxynivalenol (DON) levels of germ, oils and meals were analyzed. Results showed that maize germ with high initial moisture contents (11.82, 17.97%) or kept at high humidity (95%) became badly moldy at the end of storage. Meanwhile, the qualities of these germ and oils showed great changes. However, the ZEN and DON contents of this maize germ, oils and meals stayed at similar levels ( < 0.05). Therefore, the storage could produce influence on the qualities of germ and oils, but showed limited effect on the DON and ZEN levels of germ and their processing products. According to this study, the storage condition of germ with no more than 9% moisture content and no higher than 75% humidity was recommended. This study would be benefit for the control of germ qualities and safety during its storage.
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http://dx.doi.org/10.3390/toxins12090535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551338PMC
August 2020

Sea Cucumber Sterol Alleviates the Lipid Accumulation in High-Fat-Fructose Diet Fed Mice.

J Agric Food Chem 2020 Sep 17;68(36):9707-9717. Epub 2020 Aug 17.

College of Food Science and Engineering, Ocean University of China, No. 5 Yushan Road, Qingdao 266003, People's Republic of China.

The effect of marine-derived sea cucumber sterol (SS) with a special sulfate group on lipid accumulation remains unknown, although phytosterol has been proved to have many biological activities, including lowering blood cholesterol. The purpose of the present study is to investigate the alleviation of SS on lipid accumulation and the possible underlying mechanism using high-fat-fructose diet fed mice. Dietary administration with SS for 8 weeks reduced significantly the body weight gain and lipid levels in serum and liver. Especially, SS was superior to phytosterol in lowering lipid accumulation due to the great promotion of fatty acid β-oxidation, the inhibition of cholesterol synthesis, and the acceleration of cholesterol efflux. The findings found that sea cucumber sterol exhibited a more significant effect than phytosterol on alleviating HFF-diet-induced lipid accumulation through regulating lipid and cholesterol metabolism, which might be attributed to the difference in the branch chain and sulfate group.
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http://dx.doi.org/10.1021/acs.jafc.0c03794DOI Listing
September 2020

Polymannuronic acid prevents dopaminergic neuronal loss via brain-gut-microbiota axis in Parkinson's disease model.

Int J Biol Macromol 2020 Dec 22;164:994-1005. Epub 2020 Jul 22.

College of Food Science and Engineering, Ocean University of China, Qingdao, China. Electronic address:

The study aims to investigate the potentially neuroprotective effects and underlying mechanisms for brown seaweed polysaccharide of polymannuronic acid (PM) against Parkinson's disease (PD) pathogenesis. PD model mice were pretreated with PM via oral gavage once per day for 4 weeks and the preventative effects of PM against neuronal loss together with its modulation on brain-gut-microbiota axis were systematically explored. The results showed PM administration improved motor functions by preventing dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc) and enhanced contents of striatal homovanillic acid (HVA), serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) and γ-aminobutyric acid (GABA) in PD mice. PM significantly alleviated inflammation in gut, brain and systemic circulation as shown by reduced levels or expressions of pro-inflammatory cytokines concurrently and inhibited mitogen-activated protein kinases (MAPK) signaling pathway in mice colon. Meanwhile, PM greatly improved integrity of intestinal barrier and blood brain barrier (BBB) as indicated by increased expressions of tight junction associated proteins in both mice colon and SNpc. Further studies indicated PM treatment resulted in changes of gut microbial compositions, together with great alterations of digestion and metabolism of dietary proteins and fats, which led to surge increase of fecal short chain fatty acids (SCFAs) in the colon of PD mice. In conclusion, pre-administration of PM could provide neuroprotective effects against PD pathogenesis by suppressing inflammation in gut, brain and systemic circulation, and by improving integrity of intestinal barrier and BBB. PM might modulate brain-gut-microbiota axis, at least in part, via gut microbiota derived SCFAs as mediators.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.07.180DOI Listing
December 2020

Effects of dietary choline, betaine, and L-carnitine on the generation of trimethylamine-N-oxide in healthy mice.

J Food Sci 2020 Jul 22;85(7):2207-2215. Epub 2020 Jun 22.

College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong, 266003, China.

Trimethylamine-N-oxide (TMAO) is considered to have negative effect on human health. Different precursors of TMAO, such as choline, betaine, and L-carnitine, are commonly found in daily foods. The aim of the present study was to compare the ability of different precursors to be metabolized into TMAO, as well as the possible effect of chronic administration with TMAO precursors on TMAO production. The rate of TMAO generation after single gavage with different precursors was L-carnitine > choline >betaine. Moreover, the serum TMAO level of mice increased more than twofold after administration with choline for 3 weeks compared with L-carnitine and betaine groups, which was accompanied by the change of intestinal flora. After the gavage of choline chloride, the production for TMAO was 2.8 and 1.6 times higher in chronic choline-treated group compared with L-carnitine and betaine groups, respectively. In addition, administration with choline increased the lowest TMAO level after intraperitoneal injection of trimethylamine (TMA) hydrochloride among the three treated groups. These findings indicated that different TMAO precursors had different ability to form TMAO in vivo, and long-term dietary intervention would affect the metabolism of precursors to generate TMA and the TMA oxidation to form TMAO, suggesting that TMAO levels in vivo could be regulated by dietary intervention. PRACTICAL APPLICATION: Diverse TMAO precursors exhibited different ability to be converted into TMAO in vivo. The ability of choline to produce TMAO was stronger than that of betaine and L-carnitine. Long-term dietary intervention would affect the metabolism of precursors to generate TMA and the TMA oxidation to form TMAO, suggesting that TMAO levels in vivo could be regulated by adjustment of dietary structure.
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http://dx.doi.org/10.1111/1750-3841.15186DOI Listing
July 2020

Dietary Trimethylamine -Oxide Exacerbated Atherosclerosis under a Low-Fat Rather than High-Fat Diet.

J Agric Food Chem 2020 Jun 10;68(25):6789-6791. Epub 2020 Jun 10.

College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong 266003, People's Republic of China.

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http://dx.doi.org/10.1021/acs.jafc.0c03190DOI Listing
June 2020

Recovery of brain DHA-containing phosphatidylserine and ethanolamine plasmalogen after dietary DHA-enriched phosphatidylcholine and phosphatidylserine in SAMP8 mice fed with high-fat diet.

Lipids Health Dis 2020 May 25;19(1):104. Epub 2020 May 25.

College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, Shandong, China.

Background: Glycerophospholipids were the main components of cerebral cortex lipids, and there was a close association between lipid homeostasis and human health. It has been reported that dietary DHA-enriched phosphatidylcholine (DHA-PC) and phosphatidylserine (DHA-PS) could improve brain function. However, it was unclear that whether supplementation of DHA-PC and DHA-PS could change lipid profiles in the brain of dementia animals.

Methods: SAMP8 mice was fed with different diet patterns for 2 months, including high-fat diet and low-fat diet. After intervention with DHA-PC and DHA-PS for another 2 months, the lipid profile in cerebral cortex was determined by lipidomics in dementia mice.

Results: High-fat diet could significantly decrease the levels of DHA-containing PS/pPE, DPA-containing PS, and AA-containing PE, which might exhibit the potential of lipid biomarkers for the prevention and diagnosis of AD. Notably, DHA-PC and DHA-PS remarkably recovered the lipid homeostasis in dementia mice. These might provide a potential novel therapy strategy and direction of dietary intervention for patients with cognitive decline.

Conclusions: DHA-PC and DHA-PS could recover the content of brain DHA-containing PS and pPE in SAMP8 mice fed with high-fat diet.
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http://dx.doi.org/10.1186/s12944-020-01253-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249346PMC
May 2020

Eicosapentaenoic Acid-Enriched Phosphoethanolamine Plasmalogens Alleviated Atherosclerosis by Remodeling Gut Microbiota to Regulate Bile Acid Metabolism in LDLR Mice.

J Agric Food Chem 2020 May 4;68(19):5339-5348. Epub 2020 May 4.

College of Food Science and Engineering, Ocean University of China, No. 5 Yushan Road, Qingdao 266003, Shandong Province, P. R. China.

Eicosapentaenoic acid (EPA)-enriched phosphoethanolamine plasmalogens (EPA-PlsEtns) might be retained in the intestine rich in gut microbiota for a long time after treatment. It reminded us that EPA-PlsEtns might affect intestinal microbiota composition and its metabolites, which have been identified as a contributing factor in the development of cardiovascular diseases. In the present study, EPA-PlsEtn administration for 8 weeks significantly reduced the atherosclerotic lesion area in low-density lipoprotein receptor deficient (LDLR) mice. Notably, the serum total cholesterol and low-density lipoprotein cholesterol levels were significantly reduced by 33.6 and 38.2%, respectively, by EPA-PlsEtns instead of EPA in the form of ethyl ester (EPA-EE) treatment compared with the model group. EPA-PlsEtn administration also increased total neutral sterol and bile acids in feces by 92 and 39%, respectively, rather than EPA-EE. Mechanistically, EPA-PlsEtns might affect the abundance of gut microbiota contributing to the alteration of bile acid profiles, which might further accelerate bile acid synthesis via increasing cholesterol 7 α-hydroxylase expression induced by the inhibition of farnesoid X receptor activation.
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http://dx.doi.org/10.1021/acs.jafc.9b08296DOI Listing
May 2020

A pilot study on the effects of DHA/EPA-enriched phospholipids on aerobic and anaerobic exercises in mice.

Food Funct 2020 Feb;11(2):1441-1454

College of Food Science and Engineering, Ocean University of China, No. 5 Yushan Road, Qingdao 266003, P. R. China.

The beneficial effects of nonpolar DHA/EPA in triacylglycerol (TG) and ethyl ester (EE) forms as well as terrestrial phospholipids on physical fatigue have been widely reported. However, the results involving the effects were inconsistent, and the reason might be that the differences in physical fatigue induced by aerobic and anaerobic exercises were usually ignored. In addition, it has been reported the significant improvement of DHA/EPA esterified to phospholipids (DHA/EPA-PLs) on many fields but not physical fatigue. Therefore, the effects of DHA/EPA-PLs on physical fatigue induced by aerobic and anaerobic exercises were evaluated and compared with those of l-carnitine and astaxanthin using swimming and running exhaustion tests in mice, respectively. The results indicated that DHA/EPA-PLs and l-carnitine have significant effects on the performance of aerobic exercise, while astaxanthin had remarkable effects on the performance of anaerobic exercise. The possible underlying mechanisms indicated that DHA/EPA-PLs significantly promoted the carbohydrate and lipid metabolism as well as the mitochondrial respiratory chain and tricarboxylic acid cycle in muscles. The study presented a potential novel candidate or targeted dietary patterns for alleviating physical fatigue.
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http://dx.doi.org/10.1039/c9fo02489aDOI Listing
February 2020

Native κ-carrageenan induced-colitis is related to host intestinal microecology.

Int J Biol Macromol 2020 Mar 8;147:284-294. Epub 2020 Jan 8.

Human Health Research Laboratory, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, Shandong, China. Electronic address:

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, has gradually emerged as a public health challenge worldwide. Carrageenan is a popular food additive that has been in use for decades. However, controversy exists regarding to the safety of carrageenan due to its exacerbation of colitis in experimental models. In this study, we studied the effects of vehicle and host intestinal microflora on carrageenan inflammatory properties in C57BL/6 J mice. We found that in high-fat diet model, native carrageenan in drinking water increased the disease activity index (DAI), myeloperoxidase (MPO) activity and the mRNA expression of TLR4 in colon, whereas carrageenan-supplemented diet has no visible effects. However, no signs of colitis were observed under low-fat diet regardless of the mode of vehicle used. Moreover, we discovered that carrageenan-induced colitis in high-fat diet model was robustly correlated with changes in the composition of gut microbiota, specifically Alistipes finegoldii and Bacteroides acidifaciens. Hence, we propose that the inflammatory property of carrageenan is influenced greatly by its intake form via modification of host intestinal microecology.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.01.072DOI Listing
March 2020

Characterization and Absorption Kinetics of a Novel Multifunctional Nanoliposome Stabilized by Sea Cucumber Saponins Instead of Cholesterol.

J Agric Food Chem 2020 Jan 23;68(2):642-651. Epub 2019 Dec 23.

College of Food Science and Engineering , Ocean University of China , 5 Yushan Road , Qingdao 266003 , P. R. China.

Cholesterol was usually used to stabilize liposome, although there have been controversies on the relationship between dietary cholesterol and health. The present study aimed to prepare a novel multifunctional nanoliposomes stabilized by sea cucumber-derived saponins using ultrasound-assisted film dispersion method. A novel uniform liposome with a mass ratio of egg yolk lecithin/sea cucumber saponins at 75:25 was successfully prepared to encapsulate saponin, and the particle size was 164.8 ± 1.70 nm with a PDI value of 0.214 ± 0.022 and zeta potential of -15.97 ± 1.23 mV. The digestion and absorption results in vivo showed that the dietary saponins in liposome form could delay the peak time of saponins and prolong their residence time in the serum. Moreover, saponins were more easily converted into their corresponding metabolites after administration with saponins in the liposome form. The novel liposome as an efficient carrier with multiple functions had great potential in the development of functional food and biomedical applications.
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http://dx.doi.org/10.1021/acs.jafc.9b06460DOI Listing
January 2020

Application of Plackett-Burman Design in Screening of Natural Antioxidants Suitable for Anchovy Oil.

Antioxidants (Basel) 2019 Dec 6;8(12). Epub 2019 Dec 6.

College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.

Considering the safety of synthetic antioxidants, more and more natural antioxidants have been developed and utilized in foods. This study aimed to screen out a natural antioxidant combination from many antioxidants, which could significantly affect the oxidation stability of anchovy oil, while Plackett-Burman design (PBD) methodology was employed in this screening. According to the statistical results of this design, sesamol, dihydromyricetin, teapolyphenol, and rosemary acid were four significant parameters on the oxidation stability of anchovy oil. Moreover, dihydromyricetin presented the best antioxidant effect among nine kinds of selected antioxidants when they were used alone in anchovy oil. Meanwhile, a combination including sesamol (0.02%), teapolyphenol (0.02%). and rosemary acid (0.02%) was adopted, and its antioxidant ability was similar to that of tert-butylhydroquinone (TBHQ). Additionally, phytic acid as a synergist was used and combined with sesamol, and the antioxidant ability of this combination was better than that of TBHQ. This study presented a reference for the industrial applications of natural antioxidants and synergists in anchovy oil.
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http://dx.doi.org/10.3390/antiox8120627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943644PMC
December 2019

Digestion, Absorption, and Metabolism Characteristics of EPA-Enriched Phosphoethanolamine Plasmalogens Based on Gastrointestinal Functions in Healthy Mice.

J Agric Food Chem 2019 Nov 6;67(46):12786-12795. Epub 2019 Nov 6.

College of Food Science and Engineering , Ocean University of China , No. 5 Yushan Road , Qingdao , Shandong 266003 , People's Republic of China.

EPA-enriched phosphoethanolamine plasmalogens (EPA-pPE), widely present in marine creatures, is a unique glycerophospholipid with EPA at the sn-2 position of the glycerol backbone. EPA-pPE has been reported to exhibit numerous distinctive bioactivities. However, the digestion, absorption, and metabolism characteristics of EPA-pPE in vivo are not clear, which restrict the molecular mechanism analysis related to its distinctive activities. The aim of the present study was to illustrate the digestion, absorption, and metabolism characteristics of EPA-pPE by lipid analysis in serum, intestinal wall, and content after oral administration of EPA-pPE emulsion. Results showed the EPA percentage of total fatty acids in serum was increasing over time, with two peaks at 5 and 10 h by 1.89 ± 0.2 and 2.58 ± 0.27, respectively, and then fell from 1.89 ± 0.17 at 10 h to 1.35 ± 0.16 at 16 h. In small intestinal content, EPA-pPE was hydrolyzed to lyso-phospholipids and EPA by phospholipases A2 and the vinyl ether bond was retained at the sn-1 position. The released EPA could be quickly taken up into the enterocytes and enter circulation. The comparison of simulated digestion in vitro showed that the distinct digestion and absorption process of EPA-pPE was a unique phenomenon. EPA could be retained in serum at a high level for a substantial period of time, which suggested that EPA-pPE was not just a short-lived circulating molecule.
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http://dx.doi.org/10.1021/acs.jafc.9b06072DOI Listing
November 2019

Health benefits of dietary marine DHA/EPA-enriched glycerophospholipids.

Prog Lipid Res 2019 07 20;75:100997. Epub 2019 Aug 20.

College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong 266003, China; Qingdao National Laboratory for Marine Science and Technology, Laboratory of Marine Drugs & Biological Products, Qingdao, Shandong 266237, China. Electronic address:

A typical feature of marine foods is that they are rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which have formed a large-scale global industry. DHA/EPA phospholipids (PLs) are ubiquitous in marine foods and are the main DHA/EPA molecular forms in fish roe, shrimp and shellfish. Much attention has been focused on the bioavailability and health benefits that are influenced by the type and esterified form of dietary fatty acids. Recently, numerous findings have suggested that dietary DHA/EPA-PLs are superior to the triacylglycerol (TAG) or ethyl ester forms in exerting their functional properties through specific mechanisms of action. However, there is no comprehensive review covering the health benefits of dietary marine DHA/EPA-enriched PLs. In this paper, we review publications on the nutritional functions of DHA/EPA-enriched glycerophospholipids, including the effects on brain function, antitumor activity, lipid metabolism, and glucose metabolism. The current research status regarding the active ingredients, sources, models, treatment, duration, and mechanisms are presented. In addition, the way in which the structure-activity relationship of DHA/EPA-PLs is affected by ester-bond structure at the sn-1 position, fatty acid at the sn-2 position and polar head group at the sn-3 position is also reviewed. DHA/EPA-PLs are one of the major n-3 long-chain polyunsaturated fatty acid dietary forms in our diet, and we should maximize the ability to fully exploit the nutritional properties of DHA/EPA.
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http://dx.doi.org/10.1016/j.plipres.2019.100997DOI Listing
July 2019

Eicosapentaenoic acid in the form of phospholipids exerts superior anti-atherosclerosis effects to its triglyceride form in ApoE mice.

Food Funct 2019 Jul;10(7):4177-4188

College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, Shandong, China.

Dietary eicosapentaenoic acid (EPA), a main component of fish oil, has been proved to reduce the risk of cardiovascular disease. The purpose of this study was to investigate whether the anti-atherosclerosis effect of fish oil enriched with EPA partially relied on its chemical groups at the sn-3 position. Male ApoE-/- mice were divided into three groups and were fed a high-fat diet (Model) or a high-fat diet containing EPA incorporated into phospholipids (EPA-PL) or triglycerides (EPA-TG), respectively. Compared with the model group, a decrease in the area of atherosclerosis lesions at the aorta was observed in both EPA-treated groups, in which EPA-PL was superior to EPA-TG. Notably, EPA-PL exhibited lower serum and hepatic lipid levels than the model group, whereas EPA-TG only reduced the hepatic triglyceride level. Interestingly, only EPA-PL treatment regulated the expression of genes involved in cholesterol metabolism. In addition, EPA-PL and EPA-TG suppressed the inflammation markers in the aorta and circulation. In conclusion, EPA-PL was superior to EPA-TG in reducing lesion progression by modulating the hepatic lipid metabolism, as well as decreasing the inflammation in the artery wall and circulatory system, which might be attributed to their structural differences at the sn-3 position.
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http://dx.doi.org/10.1039/c9fo00868cDOI Listing
July 2019

Synergistic effect of sea cucumber saponins and EPA-enriched phospholipids on insulin resistance in high-fat diet-induced obese mice.

Food Funct 2019 Jul;10(7):3955-3964

College of Food Science and Engineering, Ocean University of China, No. 5 Yushan Road, Qingdao 266003, P. R. China. and Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, P. R. China.

Sea cucumber saponins (SCS) exhibit a significant effect on ameliorating glucose and lipid disorders by inhibiting fatty acid biosynthesis; however, high cytotoxicity and hemolytic activity limit their application. Eicosapentaenoic acid-enriched phospholipids (EPA-PL) significantly ameliorate insulin resistance and elevate the level of hepatic lipolysis, which may have a synergistic effect with SCS in alleviating obesity-related insulin resistance via multiple mechanisms. In the present study, high-fat diet-induced male C57BL/6J mice with obesity-related insulin resistance were used to evaluate the synergistic effect of SCS and EPA-PL on alleviating the insulin resistance. Results show that the combination of SCS and EPA-PL at a half dose exhibited a significant improvement on glucose intolerance and systematic insulin sensitivity than SCS or EPA-PL alone. Moreover, the half dose-combination remarkably inhibited the macrophage infiltration (F4/80) to white adipose tissue (WAT) and significantly down-regulated the level of MCP1, TNF-α and IL-6 compared with SCS and EPA-PL alone. Consequently, the combined administration not only decreased hepatic gluconeogenesis and increased hepatic glycogen synthesis (P < 0.05), but also stimulated the glucose uptake in WAT and muscle (P < 0.05). Nevertheless, neither SCS or EPA-PL alone exhibited any effect on the glucose uptake. The combination of SCS and EPA-PL contributed to a synergistic effect on alleviating the obesity-related insulin resistance due to the amelioration of an inflammation-centric peripheral insulin response.
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http://dx.doi.org/10.1039/c9fo01147aDOI Listing
July 2019

A Pilot Study on Anti-Obesity Mechanisms of : The Role of Native κ-Carrageenan and the Leftover Sans-Carrageenan Fraction.

Nutrients 2019 May 21;11(5). Epub 2019 May 21.

Human Health Research Laboratory, College of Food Science and Engineering, University of China, Qingdao 266003, Shandong, China.

is a commercially important edible red alga widely cultivated for carrageenan production. Here, we aimed to investigate the anti-obesity mechanism of by comparing the effects of whole seaweed (T), extracted native κ-carrageenan (CGN), and the leftover fraction sans-carrageenan (SCGN) supplementations (5%, /) on diet-induced obese C57BL/6J mice. A high-fat diet induced both a raised body fat percentage and serum cholesterol level, increased adipocytes size, abnormal levels of adipocytokines, and promoted gut dysbiosis. Our results showed that, overall, both CGN and SCGN were more effective in reversing obesity and related metabolic syndromes to normal levels than T. Furthermore, these findings suggested that CGN- and SCGN-modulated gut dysbiosis induced by a high-fat diet, which may play an influencing role in adiponectin dysregulation. Our data also showed some evidence that CGN and SCGN have distinct effects on selected genes involved in lipid metabolism. In conclusion, both κ-carrageenan and SCGN have novel anti-obesity potential with possible different mechanisms of action.
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http://dx.doi.org/10.3390/nu11051133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566674PMC
May 2019

DHA-PC protects kidneys against cisplatin-induced toxicity and its underlying mechanisms in mice.

Food Funct 2019 Mar;10(3):1571-1581

College of Food Science and Engineering, Ocean University of China, No. 5 Yushan Road, Qingdao, Shandong Province 266003, PR China.

Cisplatin is an effective chemotherapeutic agent used in the treatment of various cancers. However, its use is usually complicated by nephrotoxic side effects, which limit its clinical application. Interestingly, DHA supplementation has been found to exhibit anticancer activity without any side effects. It is noted that DHA-PC has been applied in the treatment of kidney diseases. Our aim in the current study was to investigate whether DHA-PC treatment could alleviate cisplatin-induced nephrotoxicity using a Balb/c mice model. Our results showed that DHA-PC could significantly prolong the survival time, while the traditional DHA had no remarkable changes. In addition, short supplements of DHA-PC alleviated the cisplatin-induced kidney dysfunction, such as increased levels of blood urea nitrogen and creatinine. DHA-PC could protect the kidneys against cisplatin-induced toxicity, which might be attributed to the sirtuin 1 activation and the inhibition of oxidative stress and apoptosis. These findings suggest that DHA-PC might be a new dietary strategy for the treatment of nephrotoxicity.
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http://dx.doi.org/10.1039/c8fo02386gDOI Listing
March 2019

Comparative studies of DHA-enriched phosphatidylcholine and recombination of DHA-ethyl ester with egg phosphatidylcholine on ameliorating memory and cognitive deficiency in SAMP8 mice.

Food Funct 2019 Feb;10(2):938-950

College of Food Science and Engineering, Ocean University of China, No. 5 Yushan Road, Qingdao 266003, P. R. China.

Docosahexaenoic acid-enriched phospholipids (DHA-PLs) are important bioactive components from marine foods, and are barely obtained by people living inland due to limited sources of commercial DHA-PLs compared to commercial DHA-TG and DHA-EE fish oil. Therefore, it is of significance to develop substitutions of DHA-PLs. In the present study, we comparatively investigated the effects of DHA-phosphatidylcholine (PC) and the recombination of DHA-ethyl ester (EE) with egg PC on improving the dysfunction of memory and cognition in senescence-accelerated prone 8 (SAMP8) mice and illustrated the possible underlying mechanisms. Results showed that DHA-PC exhibited stronger effects than the recombination of DHA-EE with egg PC on improving the dysfunction of memory and cognition via suppressing Aβ generation, neuro-inflammation and apoptosis, and improving neurotrophins. These findings suggested that DHA-PLs (DHA-PC) could not be substituted by the recombination of commercial fish oil with DHA-free PC in alleviating age-related memory loss and cognitive deficiency in SAMP8 mice, which provided a reference for the prevention and treatment of neurodegenerative diseases.
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http://dx.doi.org/10.1039/c8fo01822gDOI Listing
February 2019

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

Mol Nutr Food Res 2019 03 12;63(5):e1800707. Epub 2018 Dec 12.

College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, Shandong, China.

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 β-amyloid (Aβ)-induced cognitive impairment is investigated.

Methods And Results: Male SD rats receive a ventricle injection Aβ peptide to establish an Alzheimer's disease model. Then, the protective effects of Cer against Aβ -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 Aβ -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 Aβ -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 Aβ -induced synaptic dysfunction. Furthermore, Cer attenuates Aβ -induced tau hyperphosphorylation by activating the PI3K/Akt/GSK3β signaling pathway.

Conclusion: Sea cucumber cerebrosides possess neuroprotective effects against Aβ -triggered cognitive deficits, which may be a potential nutritional preventive strategy for neurodegenerative diseases.
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http://dx.doi.org/10.1002/mnfr.201800707DOI Listing
March 2019