Endogenous biosynthesis of docosahexaenoic acid(DHA)regulates fish oocyte maturation by promoting pregnenolone production

Omega-3 polyunsaturated fatty acids(n-3 PUFAs),particularly docosahexaenoic acid(22:6n-3,DHA),play crucial roles in the reproductive health of vertebrates,including humans.Nevertheless,the underlying mechanism related to this phenomenon remains largely unknown.In this study,we employed two zebrafish genetic models,i.e.,elovl2^(-/-)mutant as an endogenous DHAdeficient model and fat1(omega-3 desaturase encoding gene)transgenic zebrafish as an endogenous DHA-rich model,to investigate the effects of DHA on oocyte maturation and quality.Results show that the elovl2^(-/-)mutants had much lower fecundity and poorer oocyte quality than the wild-type controls,while the fat1 zebrafish had higher fecundity and better oocyte quality than wildtype controls.DHA deficiency in elovl2^(-/-)embryos led to defects in egg activation,poor microtubule stability,and reduced pregnenolone levels.Further study revealed that DHA promoted pregnenolone synthesis by enhancing transcription of cyp11a1,which encodes the cholesterol side-chain cleavage enzyme,thereby stabilizing microtubule assembly during oogenesis.In turn,the hypothalamic-pituitary-gonadal axis was enhanced by DHA.In conclusion,using two unique genetic models,our findings demonstrate that endogenously synthesized DHA promotes oocyte maturation and quality by promoting pregnenolone production via transcriptional regulation of cyp11a1.

Encapsulation of docosahexaenoic acid (DHA) using self-assembling food-derived proteins for efficient biological functions

Docosahexaenoic acid(DHA;22n-6)possesses multiple biological functions, including antioxidant activity and ameliorating hypertriglyceridemia. However, the application of DHA has been limited due to poor aqueous solubility and susceptible to oxidation. Here, ovalbumin(O), myosin(M), 7S soy globulin(S), and β-lactoglobulin(β), hydrolyzed by chymotrypsin, self-assembled into micelles, respectively. Adding incremental DHA to micelles caused endogenous fluorescence quenching of O, M, S, and β micelles, implying successful incorporation of DHA into hydrophobic cores of micelles(O(DHA), M(DHA), S(DHA), and β(DHA)). The results showed that micelles provided spatial stability and improved solubility, and stability against thermal and ultraviolet(UV)light for DHA. The uptake of DHA from M(DHA), β(DHA), O(DHA), and S(DHA)was 3.27-, 3.91-, 2.7-, and 3.95-fold higher, respectively, than that of DHA by Caco-2 cells. Encapsulation in micelles increased DHA aqueous solubility and uptake, which enhanced cellular endogenous antioxidant defense. Meanwhile, increased uptake of DHA was verified by HepG2 cells, and O, M, S, and β micelles were proven to increase DHA uptake to reduce lipid deposition. Our findings strongly support the possibility that O, M, S, and β micelles can be regarded as a carrier for loading DHA.

High Sn-2 Docosahexaenoic Acid Lipids for Brain Benefits, and Their Enzymatic Syntheses: A Review

The normal development and maintenance of central neural functions are highly correlated with the amount of docosahexaenoic acid(DHA;ω-3 fatty acid)accumulated in the brain.DHA incorporated at the sn-2 position of lipids is well absorbed by intestinal mucosa and utilized efficiently in vivo.However,modern consumers have a reduced direct intake of DHA and increased intake of saturated fats or ω-6 fatty acid oils,resulting in behavioral and neurophysiological deficits.To provide an understanding of the integrated beneficial effects of DHA on the human brain,this review introduces the positional difference(sn-2 and sn-1,3 positions)of DHA on a glycerol skeleton in natural fats and oils,and further discusses the possible functional mechanism regarding DHA supplementation and the gut-brain axis.The multiple bidirectional routes in this axis offer a novel insight into the interaction between DHA supplementation,the gut microbiota,and brain health.To achieve high sn-2 DHA in diets,it is suggested that sn-2 DHA lipids be enzymatically produced in more efficient and economical ways by improving the specific activities of lipases and optimizing the purification procedures.These types of diets will benefit individuals with strong needs for sn-2 ω-3 lipids such as infants,children,and pregnant and lactating women.

Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells

AIM： To investigate the impact of arachidonic acid （AA） and docosahexaenoic acid （DHA） and their combination on colon cancer cell growth. METHODS： The LS-174T colon cancer cell line was used to study the role of the prostaglandin precursor AA and the omega-3 polyunsaturated fatty acid DHA on cell growth. Cell viability was assessed in XTT assays. For analysis of cell cycle and cell death, flow cytometry and DAPI staining were applied. Expression of cyclooxygenase-2 （COX-2）, p21 and bcl-2 in ceils incubated with AA or DHA was examined by real-time RT-PCR. Prostaglandin E2 （PGE2） generation in the presence of AA and DHA was measured using a PGE2- ELISA. RESULTS： AA increased cell growth, whereas DHA reduced viability of LS 174T cells in a time- and dosedependent manner. Furthermore, DHA down- regulated mRNA of bcl-2 and up-regulated p21. Interestingly, DHA was able to suppress AA-induced cell proliferation and significantly lowered AA-derived PGE2 formation. DHA also down-regulated COX-2 expression. In addition to the effect on PGE2 formation, DHA directly reduced PGE2-induced cell proliferation in a dosedependent manner. CONCLUSION： These results suggest that DHA can inhibit the pro-proliferative effect of abundant AA or PGE2.

Moderating effect of synthesized docosahexaenoic acid-enriched phosphatidylcholine on production of Th1 and Th2 cytokine in lipopolysaccharide-induced inflammation

Objective: To evaluate effects of docosahexaenoic acid-enriched phosphatidylcholine(DHAPC) on cytokine production induced by lipopolysaccharide(LPS). Methods: The culture supernatants of splenocytes exposed to DHA-PC along with LPS were harvested to determine the production of Th 1(IFN-kines. Cytokines were m毭 and IL-2) and Th2 [IL-4, IL-5, IL-6 and IL-12/IL-23(p40)] cytoeasured using ELISA. Results: Co-administration of DHAPC with LPS resulted in significantly lower IL-2 expression compared to that observed with administration of only LPS(P<0.01). Treatment with DHA-PC and LPS significantly increased IL-5 expression(P<0.01). Moreover, co-administration of DHA-PC with LPS significantly decreased IL-6 and IL-12/IL-23(p40) expressions compared to that observed with administration of only LPS(P<0.01). Conclusions: Our results suggest that DHA-PC inhibits pro-inflammatory cytokines [IL-2, IL-6 and IL-12/IL-23(p40)] expression on induction of inflammation.

Protective effects of docosahexaenoic acid against non-alcoholic hepatic steatosis through activating of JAK2/STAT3 signaling pathway

Non-alcoholic fatty liver disease is the most common cause of hepatic dysfunction.In the present study,human normal hepatocyte L02 cells were treated with 50%fetal bovine serum to induce the formation of hepatic steatosis in vitro,and then the cells were treated with docosahexaenoic acid to investigate its protective effect on Non-alcoholic fatty liver disease.Our results showed that 50%of fetal bovine serum significantly induced intracellular lipid accumulation and hepatocyte fatty degeneration within 48 h.The expression level of adipose formation-related genes was significantly up-regulated,such as PPARγ,C/EBPαand SREBP-1;meanwhile,the content of cellular total lipid,total cholesterol and triglycerides were significantly increased after 50%fetal bovine serum treatment.Interestingly,docosahexaenoic acid treatment could inhibit FBS-induced intracellular lipid accumulation in L02 cells and the expression of lipogenic genes.Moreover,docosahexaenoic acid treatment could reduce hepatic steatosis-induced oxidative stress and endoplasmic reticulum stress response,and these responses were shown by the modification of antioxidant enzyme activities and GRP78,CHOP expression.In addition,the results showed that docosahexaenoic acid can activate the JAK2/STAT3 signaling pathway in fatty liver L02 cell;inhibition of JAK2/STAT3 signaling pathway by WP1066 abolished the beneficial effects of docosahexaenoic acid on hepatic steatosis accompanied with the increased expression of lipogenic genes and endoplasmic reticulum stress response.Above all,the present study showed that docosahexaenoic acid can alleviate non-alcoholic hepatic steatosis by activating JAK2/STAT3 signaling pathway.

Fatty Acid Composition and Digestive Enzyme Activities of Rainbow Trout in Response to Dietary Docosahexaenoic Acid(DHA)and Eicosapentaenoic Acid(EPA)During Salinity Acclimation

This physiological study aimed to evaluate the effects of dietary docosahexaenoic acid(DHA)and eicosapentaenoic acid(EPA)on the fatty acid composition and digestive enzyme activities of rainbow trout(Oncorhynchus mykiss)during salinity acclimation.Rainbow trout with an average initial weight of 90.61 g±9.25 g were fed diets with the quantities of DHA and EPA equaling to 0.54%,0.95%,1.40%and 1.79%(abbreviated as DE-0.54,DE-0.95,DE-1.40,and DE-1.79,respectively)for eight weeks,after which the gastric and intestinal fatty acids composition were analyzed.Subsequently,the fish underwent salinity acclimation.On days 1,4,7,and 14 after the freshwater was replaced by seawater and at the end of the 8-week period,gastric and intestinal digestive enzyme activities were determined.The results showed that the gastric and intestinal DHA and EPA contents of the fish were positively correlated to their dietary DHA and EPA levels.Low dietary DHA and EPA levels inhibited the protease activity of rainbow trout.Fish in the DE-0.54 group increased the lipase activity to enhance the utilization of lipids maybe due to the inadequate essential fatty acids for fish in this group.Hence,rainbow trout in the DE-0.54 group failed to maintain suitable activities of digestive enzymes after salinity acclimation.Therefore,a diet with minimum 0.95%DHA and EPA levels is necessary for rainbow trout during salinity acclimation.

Fortification of pork loins with docosahexaenoic acid(DHA) and its effect on flavour

Pork is traditionally low in docosahexanoic acid （DHA, C22：6n-3） and deficient in omega-3 fats for a balanced human diet. DHA as triglycerides was commercially prepared from the microalgae Schizochytfium and injected into fresh pork loins. Treatments of a mixed brine control （CON）, 3.1% sunflower oil in mixed brine （SF） and a 3.1% DHA oil in mixed brine （DHA） were injected into pork loins at 10 mL/100 g and grilled at 205℃. After cooking, the CON and SF pork loins contained 0.03 to 0.05 mg DHA/g of pork and the DHA injected loins contained approximately 1.46 mg DHA/g. This also changed the fatty acid profile of omega-6：omega-3 from, 5 to 1 in the CON pork, to a ratio of 1.7 to 1 in DHA pork. The appearance, odor, oxidation rates and sensory taste, as judged by a trained panel, determined the DHA injected meat to be, ＇slightly desirable＇ and gave lower ＇off flavour＇ scores, relative to the CON and SF injected pork. Pork can be fortified with DHA oil to 146 mg/100 g serving, which would meet half the recommended daily omega 3 fatty acid requirements for adult humans and would be desirable in taste.

Pilot trial evaluating maternal docosahexaenoic acid consumption during pregnancy: Decreased postpartum depressive symptomatology

Objective:Docosahexaenoic acid(DHA,22:6,n-3)is a major structural component of neural tissue critical to neurotransmission and mood regulation.Poor maternal dietary intake coupled with accelerated maternal-fetal transfer of DHA compound risk for maternal deficiency.The objective of this investigation was to determine if maternal DHA supplementation is efficacious in reducing symptoms of postpartum depression.Methods:This pilot investigation was a randomized,double-blinded,placebo controlled investigation of the role of DHA in preventing risk for postpartum depression.Women were assigned to:i)Placebo(no DHA,corn oil capsule),ii)DHA(300 mg DHA,fish oil capsule).Capsules were consumed from 24 to 40 weeks gestation(1 capsule 5 days/week).Forty-two participants were recruited(n=20,intervention;n=22,placebo).Maternal DHA status and depressive symptoms were followed from 24 to 40 weeks gestation using the Center for Epidemiologic Studies Depression Scale(CES-D)and the Postpartum Depression Screening Scale(PDSS)from 2 weeks to 6 months postpartum.Results:PDSS total scores were significantly lower(p=0.016;46.03±2.17,intervention vs.52.11±2.4,placebo)in the intervention group with less anxiety/insecurity(p=0.03),emotional lability(p=0.04)and loss of self(p=0.02).Conclusions:Women in the DHA intervention group had fewer symptoms of postpartum depression compared to the placebo group.These results support the notion that the consumption of DHA by pregnant women can be efficacious in preventing depressive symptoms and highlight a need for further larger-scale investigations using the PDSS in tandem with a diagnostic evaluation.

Docosahexaenoic acid-rich fish oil prevented insulin resistance by modulating gut microbiome and promoting colonic peptide YY expression in diet-induced obesity mice

It is unclear how docosahexaenoic acid(DHA)improves insulin resistance via modulating gut microbiome in obese individuals.We used diet-induced obesity(DIO)mice as a model to study the effects of DHA-rich fish oil(DHA-FO)on host metabolic disorders and colonic microbiome.DHA-FO reduced fat deposition,regulated lipid profiles and alleviated insulin resistance in DIO mice.Probably because DHA-FO prevented the permeation of lipopolysaccharide across intestinal epithelial barrier,and promoted peptide YY(PYY)secretion via the mediation of short chain fatty acids receptor(FFAR2)in colon.Furthermore,DHA-FO might regulate PYY expression by reversing microbial dysbiosis,including increasing the abundance ofAkkermansia muciniphila and Lactobacillus,and suppressing the growth of Helicobacter.DHA-FO also altered gut microbial function(e.g."linoleic acid metabolism")associated with PYY expression(r>0.80,P<0.05).Herein,DHA-FO enhanced insulin action on glucose metabolism by altering gut microbiome and facilitating colonic PYY expression in DIO mice.

Identity and Safety of a Novel <i>Aurantiochytrium sp.</i>for Terrestrial Heterotrophic Docosahexaenoic Acid Production

The objective of the studies in this paper was to expand on the published toxicological assessment of Aurantiochytrium limacinum (AURA) with further strain characterization and to investigate the potential for the biomass or extracted oil to have antimicrobial properties or undesirable substances. AURA is being investigated as a novel source of the omega-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) for enriching foods of animal origin by means of feed supplementation. In the first studies, we provided the 18S rRNA identification of the novel marine isolated thraustochytrid, established the nutritional composition of AURA biomass for application as a food or feed ingredient including proximate analysis and fatty acid profiling, and confirmed the DHA production potential of the strain. We determined through minimum inhibitory concentration (MIC) analysis that the unextracted AURA biomass was safe, showing no antimicrobial influence and no evidence of any deleterious effects of this product or its extracts at concentrations up to 1% w/w on the reference human intestinal bacteria tested. This would indicate that AURA should not stimulate selective pressure on the commensal microbiota and is therefore unlikely to aid development of antimicrobial resistance and the concomitant harm to humans and animals. Further analysis revealed that the AURA biomass produced through industrial heterotrophic fermentation was free from undesirables;toxic marine microalgal metabolites, heavy metals, pesticides, microbial contaminants, and mycotoxins. Including heterotrophically-grown AURA in food or feed, up to 1% w/w, is a safe and environmentally beneficial strategy for DHA supplementation.

Computational Analyses of Docosahexaenoic Acid (DHA, C22:6, n-3) with Alzheimer’s Disease-Causing Amyloid Peptide Aβ1-42 Reassures Its Therapeutic Utility

The accumulation of amyloid β peptide1-42 (Aβ1-42) masses in the brains of Alzheimer’s Disease (AD) patients is associated with neuronal loss and memory deficits. We have previously reported that oral administration of docosahexaenoic acid (DHA, C22:6, n-3) significantly decreases Aβ burden in the brains of AD model rats and that direct in vitro incubation of DHA with Aβ1-42 curbs the progression of amyloid fibrillation. In the present in silico study, we investigated whether DHA computationally binds with amyloid peptides. The NMR solution structures of Aβ1-42 were downloaded from the Protein Data Bank (PDB IDs: 1Z0Q and 2BEG). The binding of DHA to Aβ peptides was assessed by molecular docking using both a flexible and rigid docking system. Thioflavin T (ThT) was used as positive control. The chemical structures of ThT and DHA were modeled and converted to the PDB format using PRODRUG. Drug-like properties of DHA were evaluated by ADME (Absorption, Distribution, Metabolism, and Excretion). DHA was found to successfully dock with Aβ1-42. Computational analyses of the binding of DHA to Aβ1-42, as evaluated by docking studies, further corroborated the inhibitory effect of DHA on in vitro Aβ1-42 fibrillogenesis and might explain the in vivo reduction of amyloid burden observed in the brains of DHA-administered AD model rats demonstrated in our previous study. These computational data suggest the potential utility of DHA as a preventive medication in Aβ-induced neurodegenerative diseases, including AD.

Improved production of docosahexaenoic acid in batch fermentation by newly-isolated strains of Schizochytrium sp.and Thraustochytriidae sp.through bioprocess optimization

Thraustochytrids,rich in docosahexaenoic acid(DHA,C22:6u3),represent a potential source of dietary fatty acids.Yet,the effect of culture conditions on growth and fatty acid composition vary widely among different thraustochytrid strains.Two different thraustochytrid strains,Schizochytrium sp.PKU#Mn4 and Thraustochytriidae sp.PKU#Mn16 were studied for their growth and DHA production characteristics under various culture conditions.Although they exhibited similar fatty acid profiles,PKU#Mn4 seemed a good candidate for industrial DHA fermentation while PKU#Mn16 displayed growth tolerance to a wide range of process conditions.Relative DHA content of 48.5%and 49.2%(relative to total fatty acids),respectively,were achieved on glycerol under their optimal flask culture conditions.Maximum DHA yield(Yp/x)of 21.0%and 18.9%and productivity of 27.6 mg/L-h and 31.9 mg/L-h were obtained,respectively,in 5-L bioreactor fermentation operated with optimal conditions and dual oxygen control strategy.A 3.4-and 2.8-fold improvement of DHA production(g/L),respectively,was achieved in this study.Overall,our study provides the potential of two thraustochytrid strains and their culture conditions for efficient production of DHA-rich oil.

Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized.This review may contribute to the development of new approaches for the treatment of neurological diseases.

Palm oil protectsα-linolenic acid from rumen biohydrogenation and muscle oxidation in cashmere goat kids

Background:In ruminants,dietary C18:3n-3 can be lost through biohydrogenation in the rumen;and C18:3n-3 that by-passes the rumen still can be lost through oxidation in muscle,theoretically reducing the deposition of C18:3n-3,the substrate for synthesis of poly-unsaturated fatty acids(n-3 LCPUFA)in muscle.In vitro studies have shown that rumen hydrogenation of C18:3n-3 is reduced by supplementation with palm oil(rich in cis-9 C18:1).In addition,in hepatocytes,studies with neonatal rats have shown that cis-9 C18:1 inhibits the oxidation of C18:3n-3.It therefore seems likely that palm oil could reduce both rumen biohydrogenation of C18:3n-3 and muscle oxidation of C18:3n-3.The present experiment tested whether the addition of palm oil to a linseed oil supplement for goat kids would prevent the losses of C18:3n-3 and thus improve the FA composition in two muscles,Longissimus dorsi and Biceps femoris.To investigate the processes involved,we studied the rumen bacterial communities and measured the mRNA expression of genes related to lipid metabolism in Longissimus dorsi.Sixty 4-month-old castrated male Albas white cashmere kids were randomly allocated among three dietary treatments.All three diets contained the same ingredients in the same proportions,but differed in their fat additives:palm oil(PMO),linseed oil(LSO)or mixed oil(MIX;2 parts linseed oil plus 1 part palm oil on a weight basis).Results:Compared with the LSO diet,the MIX diet decreased the relative abuandance of Pseudobutyrivibrio,a bacterial species that is positively related to the proportional loss rate of dietary C18:3n-3 and that has been reported to generate the ATP required for biohydrogenation(reflecting a decrease in the abundance of rumen bacteria that hydrogenate C18:3n-3 in MIX kids).In muscle,the MIX diet increased concentrations of C18:3n-3,C20:5n-3,C22:6n-3,and n-3 LCPUFA,and thus decreased the n-6/n-3 ratio;decreased the mRNA expression of CPT1β(a gene associated with fatty acid oxidation)and increased the mRNA expression of FADS1 and FADS2(genes associated with n-3 LCPUFA synthesis),compared with the LSO diet.Interestingly,compared to Longissimus dorsi,Biceps femoris had greater concentrations of PUFA,greater ratios of unsaturated fatty acids/saturated fatty acids(U/S),and poly-unsaturated fatty acids/saturated fatty acids(P/S),but a lesser concentration of saturated fatty acids(SFA).Conclusions:In cashmere goat kids,a combination of linseed and palm oils in the diet increases the muscle concentration of n-3 LCPUFA,apparently by decreasing the relative abundance of rumen bacteria that are positively related to the proportional loss rate of dietary C18:3n-3,by inhibiting mRNA expression of genes related to C18:3n-3 oxidation in muscle,and by up-regulating mRNA expression of genes related to n-3 LCPUFA synthesis in muscle,especially in Longissimus dorsi.

Polyunsaturated fatty acids and DNA methylation in colorectal cancer

Colorectal cancer(CRC) has been designated a major global problem, especially due to its high prevalence in developed countries. CRC mostly occurs sporadically(75%-80%), and only 20%-25% of patients have a family history.Several processes are involved in the development of CRC such as a combination of genetic and epigenetic alterations. Epigenetic changes, including DNA methylation play a vital role in the progression of CRC. Complex interactions between susceptibility genes and environmental factors, such as a diet and sedentary lifestyle, lead to the development of CRC. Clinical and experimental studies have confirmed the beneficial effects of dietary polyunsaturated fatty acids(PUFAs) in preventing CRC. From a mechanistic viewpoint, it has been suggested that PUFAs are pleiotropic agents that alter chromatin remodeling,membrane structure and downstream cell signaling. Moreover, PUFAs can alter the epigenome via modulation of DNA methylation. In this review, we summarize recent investigations linking PUFAs and DNA methylationassociated CRC risk.

Fatty Acid Treatment with Pure Omega-3 Eicosapentaenoic Acid Ethyl Ester for Patients with Cardiovascular Diseases: Differences between Branded (EPADEL®) and Generic Products

Background: Omega-3 polyunsaturated fatty acids (PUFAs) have some protective benefits for patients with coronary artery and cerebrovascular diseases. Eicosapentaenoic acid (EPA) drugs are prescribed as branded (B: EPADEL?) or generic products but no data exist concerning the differences in treatment outcomes between these products. Methods and Results: We investigated the differences in the serum levels of EPA, docosahexaenoic acid (DHA) and arachidonic acid (AA), and the EPA/AA ratios through blood sampling six months after daily administration of 1800 mg of EPADEL? and a generic EPA drug was initiated for 96 patients with cardiovascular diseases. All patients received these PUFA treatments while continuing with baseline therapy. After 6 months of administration, EPADEL? produced better results than the generic (G) product (EPA;baseline: 59.4 ± 25.5 μg, B: 215.5 ± 58.8 μg, G: 199.7 ± 63.8 μg, B vs G, p < 0.0005;AA;baseline: 197.4 ± 44.6 μg, B: 158.3 ± 36.3 μg, G: 163.6 ± 38.9 μg, B vs G, p < 0.02, as mean ± SD). Conclusions: There were clear differences between EPA branded and the generic products. Further study is required to determine whether the benefits from the branded product justify the higher price compared to the generic drug cost.

Selective ischemic-hemisphere targeting Ginkgolide B liposomes with improved solubility and therapeutic efficacy for cerebral ischemia-reperfusion injury

Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of drugs.Ginkgolide B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke recovery.However,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a challenge.Herein,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes stably.The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)rats.Compared to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion.Low levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and angiogenesis.In addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway.Thus,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.

DHA Depletion in Rat Brain Is Associated With Impairment on Spatial Learning and Memory

Objective To examine the effect of docosahexaenoic acid （DHA） deficiency in brain on spatial learning and memory in rats. Methods Sprague Dawley rats were fed with an n-3 fatty acid deficient diet for two generations to induce DHA depletion in brain, DHA in seven brain regions was analyzed using the gas-liquid chromatography. Morris water maze （MWM） was employed as an assessing index of spatial learning and memory in the n-3 fatty acid deficient adult rats of second generation. Results Feeding an n-3 deficient diet for two generations depleted DHA differently by 39%-63% in the seven brain regions including cerebellum, medulla, hypothalamus, striatum, hippocampus, cortex and midbrain, The MWM test showed that the n-3 deficient rats took a longer time and swam a longer distance to find the escape platform than the n-3 Adq group. Condusion The spatial learning and memory in adult rats are partially impaired by brain DHA depletion.

Nutrition and metabolism in poultry: role of lipids in early diet

Modern strains of broiler chickens are selected for fast growth and are marketed anywhere from 36 to 49 days after a21-day incubational period. For a viable healthy chick, all the necessary nutrients required for growth and development must be provided by the hen through the fertilized egg. The current feeding strategies for improved growth, health and productivity are targeted towards chicks after hatching. Considering the fact that developing chick embryo spends over 30 % of its total life span inside the hatching egg relying on nutrients deposited by the breeder hen, investigations on nutritional needs during pre-hatch period will improve embryonic health, hatchability and chick viability. In this context, investigations on hatching egg lipid quality is of utmost importance because, during incubation, egg fat is the major source of energy and sole source of essential omega-6（n-6） and omega-3（n-3） fatty acids to the chick embryo.Due to the unique roles of n-3 and n-6 fatty acids in growth, immune health, and development of central nervous system, this review will focus on the role of early exposure to essential fatty acids through maternal diet and hatching egg and its impact on progeny in meat-type broiler chickens.