Gut Microbiota Metabolite TMA May Mediate the Effects of TMAO on Glucose and Lipid Metabolism in C57BL/6J Mice.

SCOPE: Gut microbiota can convert a variety of alkaloids and TMAO into TMA, which is then transported by the blood to the liver, and converted into TMAO. In recent years, TMAO has attracted wide attention as a metabolic risk factor in cardiovascular disease, diabetes, and other diseases. However, it is still unclear about the role of gut microbial metabolite TMA in the adverse health impacts of TMAO. METHODS AND RESULTS: Male C57BL/6J is treated with intraperitoneal (i.p.) or oral TMAO for 8 weeks, the area under the OGTT curve of oral group is significantly increased by about 15% compared to the control and injection groups. Serum triglyceride levels in the oral group are significantly higher by 28.2% and 24.6% than those in the control and injection groups, respectively. Meanwhile, cholesterol content in serum is significantly elevated by 27.6% and 30.7%. Similarly, proinflammatory factors gene expressions are significantly increased with oral but not i.p. TMAO intervention. Furthermore, transformation in HepG2 cells shows that TMAO could not be converted into TMA by hepatocytes. CONCLUSION: The adverse effects of TMAO on glucose and lipid metabolism in C57BL/6J mice may act through gut microbiota metabolite TMA.

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.

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.

A Comparative Study about the Neuroprotective Effects of DHA-Enriched Phosphatidylserine and EPA-Enriched Phosphatidylserine against Oxidative Damage in Primary Hippocampal Neurons.

Nerve damage caused by accumulated oxidative stress is one of the characteristics and main mechanisms of Alzheimer's disease (AD). Previous studies have shown that phosphatidylserine (PS) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) plays a significant role in preventing and mitigating the progression of AD. However, whether DHA-PS and EPA-PS can directly protect primary hippocampal neurons against oxidative damage has not been studied. Here, the neuroprotective functions of DHA-PS and EPA-PS against H2O2/t-BHP-induced oxidative damage and the possible mechanisms were evaluated in primary hippocampal neurons. It was found that DHA-PS and EPA-PS could significantly improve cell morphology and promote the restoration of neural network structure. Further studies showed that both of them significantly alleviated oxidative stress-mediated mitochondrial dysfunction. EPA-PS significantly inhibited the phosphorylation of ERK, thus playing an anti-apoptotic role, and EPA-PS significantly increased the protein expressions of p-TrkB and p-CREB, thus playing a neuroprotective role. In addition, EPA-PS, rather than DHA-PS could enhance synaptic plasticity by increasing the expression of SYN, and both could significantly reduce the expression levels of p-GSK3ß and p-Tau. These results provide a scientific basis for the use of DHA/EPA-enriched phospholipids in the treatment of neurodegenerative diseases, and also provide a reference for the development of related functional foods.

Study on the effect of fluorinated solvent electrolyte on the active material and cycle performance of a commercial 21700-type battery.

Different electrolyte schemes were studied on the traditional commercial 21700-type battery. The effect of different fluorinated electrolytes on the cycle performance of the battery was systematically investigated. When methyl (2,2,2-trifluoroetyl) carbonate (FEMC) was introduced, due to the low conductivity of FEMC, the polarization and internal resistance of the battery increased, which leads to the increase of constant voltage charging time, leading to the cracking of the cathode material and reduction of the cycle performance. When ethyl difluoroacetate (DFEA) was introduced, the poor chemical stability caused by its low molecular energy level led to the decomposition of the electrolyte. Thus, affecting the cycle performance of the battery. However, the introduction of fluorinated solvents can form a protective film on the surface of the cathode, which can effectively inhibit the dissolution of metal elements. The fast-charging cycle of commercial batteries is generally set at 10-80% SOC, which can effectively reduce the H2 to H3 phase transformation process, and the temperature rise caused by fast-charging can also reduce the effect of electrolytic conductivity, so that the protective effect of the fluorinated solvent on the cathode material is dominant. Therefore, the fast-charging cycle performance is improved.

Supplementation of n-3 PUFAs in Adulthood Attenuated Susceptibility to Pentylenetetrazol Induced Epilepsy in Mice Fed with n-3 PUFAs Deficient Diet in Early Life.

The growth and development of the fetus and newborn throughout pregnancy and lactation are directly related to the nutritional status of the mother, which has a significant impact on the health of the offspring. The purpose of this experiment was to investigate the susceptibility of n-3 polyunsaturated fatty acid deficiency in early life to seizures in adulthood. The n-3 PUFAs-deficient mice's offspring were established and then fed with α-LNA diet, DHA-enriched ethyl ester, and DHA-enriched phospholipid-containing diets for 17 days at the age of eight weeks. During this period, animals received intraperitoneal injections of 35 mg/kg of pentylenetetrazol (PTZ) every other day for eight days. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate PTZ-induced epileptic seizures and brain disorders. Notably, nutritional supplementation with n-3 PUFAs in adulthood for 17 days could significantly recover the brain n-3 fatty acid and alleviate the epilepsy susceptibility as well as raise seizure threshold to different levels by mediating the neurotransmitter disturbance and mitochondria-dependent apoptosis, demyelination, and neuroinflammation status of the hippocampus. DHA-enriched phospholipid possessed a superior effect on alleviating the seizure compared to α-LNA and DHA-enriched ethyl ester. Dietary n-3 PUFA deficiency in early life increases the susceptibility to PTZ-induced epilepsy in adult offspring, and nutritional supplementation with n-3 PUFAs enhances the tolerance to the epileptic seizure.

Phosphatidylglucose alleviates atherosclerosis by increasing cholesterol alienation to bile acids and cholesterol efflux in ApoE-/- mice.

BACKGROUND: Phosphatidylcholine (PC) is considered to be the major dietary source for choline, which is associated with atherosclerosis progress. Thus, phosphatidylglucose (PG) was prepared by enzymatic modification of PC to investigate the effects on atherosclerosis in apolipoprotein E deficient (ApoE-/- ) mice, as well as to investigate its dose-response relationship. RESULTS: The results showed that dietary PG significantly decreased the atherosclerotic lesion area in a dose-dependent manner. Further studies found that intervention with a 0.8 g kg-1 and 2 g kg-1 PG diet for 4 months significantly decreased free cholesterol level and thus reduced total cholesterol levels in serum. The results of cholesterol distribution among lipoproteins showed that dietary PG significantly decreased low-density lipoprotein levels in ApoE-/- mice. In addition, only administration of high-dose PG significantly reduced total cholesterol levels in liver tissues by 31.2%. Furthermore, mice treated with high-dose PG had an expanded bile acid pool and increased the ratio of conjugated bile acids to unconjugated bile acids in the liver, serum and gallbladder by increasing hepatic gene expression of primary and conjugated bile acid synthesis. Additionally, low-dose and high-dose PG significantly increased total fecal sterols by 20.8% and 11.9%, respectively, by increasing sitosterol and ethylcoprostanol levels. CONCLUSION: These results indicate that PG alleviated atherosclerosis in a dose-dependent manner by increasing cholesterol alienation to bile acids and cholesterol efflux. © 2023 Society of Chemical Industry.

N-3 PUFA Deficiency from Early Life to Adulthood Exacerbated Susceptibility to Reactive Oxygen Species-Induced Testicular Dysfunction in Adult Mice.

Homeostasis of reactive oxygen species is required to maintain sperm maturation and capacitation. Docosahexaenoic acid (DHA) is accumulated in testicles and spermatozoa and has the ability to manipulate the redox status. The effects of dietary n-3 polyunsaturated fatty acid (n-3 PUFA) deficiency from early life to adulthood on the physiological and functional properties of males under the redox imbalance of testicular tissue deserve attention. The consecutive injection of hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BHP) for 15 days to induce oxidative stress in testicular tissue was used to elucidate the consequences of testicular n-3 PUFA deficiency. The results indicated that reactive oxygen species treatment in adult male mice with DHA deficiency in the testis could reduce spermatogenesis and disrupt sex hormone production, as well as trigger testicular lipid peroxidation and tissue damage. N-3 PUFA deficiency from early life to adulthood resulted in higher susceptibility to testicular dysfunction in the germinal function of supplying germ cells and the endocrine role of secreting hormones through the mechanism of aggravating mitochondria-mediated apoptosis and destruction of blood testicular barrier under oxidative stress, which might provide a basis for humans to reduce susceptibility to chronic disease and maintain reproductive health in adulthood through dietary interventions of n-3 PUFAs.

Eicosapentaenoic acid-enriched phospholipids alleviate glucose and lipid metabolism in spontaneously hypertensive rats with CD36 mutation: a precise nutrition strategy.

Previous studies have found that eicosapentaenoic acid-enriched phospholipids (EPA-PLs) alleviated glucose and lipid metabolism, which was accompanied by an increase of cluster of differentiation 36 (CD36). However, the effects of EPA-PLs on glucose and lipid metabolism in the case of CD36 mutation are unclear. Thus, spontaneously hypertensive rats/NCrl (SHR) were used as a CD36 mutation model to determine the effects of dietary 2% EPA-PLs for 4 weeks on glucose and lipid metabolism. The results showed that the intervention of EPA-PLs significantly alleviated the abnormal increase of serum free fatty acid levels and glycerol levels in SHRs. Moreover, the administration of EPA-PLs decreased the triglyceride levels and cholesterol levels by 31.1% and 37.9%, respectively, in the liver. Dietary EPA-PLs had no effect on epididymal fat weight, but EPA-PLs inhibited adipocyte hypertrophy in SHRs. Further mechanistic research found that EPA-PL pretreatment significantly reduced triacylglycerol catabolism and increased fatty acid ß-oxidation. Additionally, the administration of EPA-PLs decreased the area under the curve of the intraperitoneal glucose tolerance test and fasting serum insulin levels by activating the IRS/PI3K/AKT signaling pathway. Furthermore, EPA-PL pretreatment significantly increased the CD36 gene expression in the liver tissues, adipose tissues and muscle tissues even in the case of CD36 mutation. These results indicated that EPA-PLs alleviate glucose and lipid metabolism in the case of CD36 mutation, which provides a precise nutrition strategy for people with CD36 mutation.

N-3 PUFA Deficiency Aggravates Streptozotocin-Induced Pancreatic Injury in Mice but Dietary Supplementation with DHA/EPA Protects the Pancreas via Suppressing Inflammation, Oxidative Stress and Apoptosis.

It has been reported that dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential for the preservation of functional ß-cell mass. However, the effect of dietary n-3 PUFA deficiency on pancreatic injury and whether the supplementation of n-3 PUFA could prevent the development of pancreatic injury are still not clear. In the present study, an n-3 PUFA deficiency mouse model was established by feeding them with n-3 PUFA deficiency diets for 30 days. Results showed that n-3 PUFA deficiency aggravated streptozotocin (STZ)-induced pancreas injury by reducing the insulin level by 18.21% and the HOMA ß-cell indices by 31.13% and the area of islet by 52.58% compared with the STZ group. Moreover, pre-intervention with DHA and EPA for 15 days could alleviate STZ-induced pancreas damage by increasing the insulin level by 55.26% and 44.33%, the HOMA ß-cell indices by 118.81% and 157.26% and reversed the area of islet by 196.75% and 205.57% compared to the n-3 Def group, and the effects were significant compared to γ-linolenic acid (GLA) and alpha-linolenic acid (ALA) treatment. The possible underlying mechanisms indicated that EPA and DHA significantly reduced the ration of n-6 PUFA to n-3 PUFA and then inhibited oxidative stress, inflammation and islet ß-cell apoptosis levels in pancreas tissue. The results might provide insights into the prevention and alleviation of pancreas injury by dietary intervention with PUFAs and provide a theoretical basis for their application in functional foods.

Free astaxanthin-rich diets enhanced astaxanthin accumulation in egg yolks compared to esterified astaxanthin-rich diets.

As an oxycarotenoid with strong antioxidant properties, astaxanthin can considerably boost pigmentation and improve the nutritional value of eggs. The purpose of this study was to elucidate the comparative effects of different chemical structures of astaxanthin including free astaxanthin, monoester-enriched astaxanthin and diester-enriched astaxanthin on the nutritional enhancement of eggs within 20 days. The results showed that supplementation of free astaxanthin to laying hens was more effective in accumulating astaxanthin in egg yolks than supplementation with esterified astaxanthin. The retention rate of free astaxanthin was approximately 12.0 % at the plateau phase in egg yolk, while that of monoester-enriched and diester-enriched astaxanthin were 4.0 % and 2.5 %, respectively. Free astaxanthin possessed a high retention rate and pigmentation effect compared with esterified astaxanthin, which might provide a basis for astaxanthin enhancement in eggs and potential application in nutritional functional foods.

The synergistic effect of sea cucumber saponins and caffeine on preventing obesity in high-fat diet-fed mice by extending the action duration of caffeine.

BACKGROUND: Sea cucumber saponins (SCSs) exhibit a unique structure and high bioactivities and might have specialized implications on caffeine metabolic process by altering the activity of N-demethylation enzyme CYP1A2. The present study aimed to clarify the effects of SCS on caffeine metabolism in vivo and in vitro, as well as the synergistic anti-obesity effect of SCS and caffeine on high-fat diet-induced obese mice. RESULTS: Results found that SCS administration significantly postponed the elimination rate of caffeine and its metabolites in vivo, and further study found CYP1A2-mediated caffeine metabolism was remarkably inhibited in a dose-dependent manner in vitro. The synergistic effect of the SCS and caffeine combination could decrease the total weight of white adipose tissue by 52% compared with high-fat diet-treated group. CONCLUSION: SCS could prolong caffeine action time, and the combination of the two substances exhibited joint action on high-fat diet-induced obese mice. These findings might provide a basis for the development of functional foods and potential application using the combination of SCS and caffeine. © 2022 Society of Chemical Industry.

DHA-Enriched Phospholipids Exhibit Anti-Depressant Effects by Immune and Neuroendocrine Regulation in Mice: A Study on Dose- and Structure-Activity Relationship.

SCOPE: It has been reported that eicosapentaenoic acid (EPA), especially EPA-enriched phospholipids (EPA-PL), significantly ameliorates depression-like behavior in mice, while the corresponding effect of docosahexaenoic acid (DHA) is weak. However, it is still unclear whether the limited effect of DHA on alleviating depression is remedied by dose and chemical structure adjustment to DHA-PL. METHODS AND RESULTS: A mouse model with depression is established by chronic unpredictable mild stress (CUMS) coupled with lipopolysaccharide (LPS) challenge to simulate the infection-triggered immune perturbation during chronic stress, and the effects of dietary 0.2% EPA-PL, 0.2% DHA-PL, 0.6% DHA-PL, and 0.6% DHA-enriched ethyl ester (DHA-EE) are comparatively investigated. The results demonstrate that dietary 0.6% DHA-PL, instead of 0.2% DHA-PL and 0.6% DHA-EE, significantly rescues the depression-like behavior with similar effects to 0.2% EPA-PL. Further studies reveal that dietary DHA-PL regulates immune dysregulation, inhibits neuroinflammation by NLRP3 inflammasome, and further improves monoamine systems and the hypothalamic-pituitary-adrenal (HPA) axis. CONCLUSION: The limited effect of DHA on depression is remedied by chemical structure adjustment to DHA-PL and three-fold dose. The present findings provide a potential novel candidate or targeted dietary patterns to prevent and treat depression.

Sea Cucumber Saponins Derivatives Alleviate Hepatic Lipid Accumulation Effectively in Fatty Acids-Induced HepG2 Cells and Orotic Acid-Induced Rats.

The sulfated echinoside A (EA) and holothurin A (HA) are two prominent saponins in sea cucumber with high hemolytic activity but also superior lipid-lowering activity. Deglycosylated derivatives EA2 and HA2 exhibit low hemolysis compared to EA and HA, but their efficacies on lipid metabolism regulation remains unknown. In this study, fatty acids-treated HepG2 cells and orotic acid-treated rats were used to investigate the lipid-lowering effects of sea cucumber saponin derivatives. Both the saponin and derivatives could effectively alleviate lipid accumulation in HepG2 model, especially EA and EA2. Moreover, though the lipid-lowering effect of EA2 was not equal with EA at the same dosage of 0.05% in diet, 0.15% dosage of EA2 significantly reduced hepatic steatosis rate, liver TC and TG contents by 76%, 41.5%, and 63.7%, respectively, compared to control and reversed liver histopathological features to normal degree according to H&E stained sections. Possible mechanisms mainly included enhancement of fatty acids ß-oxidation and cholesterol catabolism through bile acids synthesis and excretion, suppression of lipogenesis and cholesterol uptake. It revealed that the efficacy of EA2 on lipid metabolism regulation was dose-dependent, and 0.15% dosage of EA2 possessed better efficacy with lower toxicity compared to 0.05% dosage of EA.

Comparative Analyses of EPA-Phosphatidylcholine, EPA-Lysophosphatidylcholine, and DHA-Lysophosphatidylcholine on DHA and EPA Repletion in n-3 PUFA-Deficient Mice.

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) play an important role in maintaining the physiological functions of tissues, and the beneficial effects of DHA/EPA in phospholipid forms have been widely reported. Although lysophosphatidylcholine (LPC) is considered to be the preferred form of DHA supplementation for the brain, the kinetics of DHA and EPA recovery and corresponding changes of n-6 docosapentaenoic acid (DPA) and arachidonic acid (AA) levels in different phospholipid molecules and different tissues after administration of EPA in phosphatidylcholine (PC) and LPC forms and DHA in the LPC form are not clear. Here, we measured the total fatty acids in tissues and fatty acid composition of different phospholipid molecules after gavage administration of equal molar amounts of EPA/DHA in mice with n-3 polyunsaturated fatty acid (PUFA) deficiency induced by maternal dietary deprivation of n-3 PUFA during pregnancy and lactation. The results showed that dietary supplementation with EPA-PC, EPA-LPC, and DHA-LPC exhibited different priorities for EPA or DHA accretion and supplementation efficiency curves in different tissues during the developing period. EPA-PC exhibited a more optimal efficacy in DHA and EPA repletion in serum and hepatic total fatty acids. In terms of DHA recovery in the brain, EPA-LPC and DHA-LPC showed great effects. Meanwhile, the DHA level in total fatty acids and major fractions of phospholipids (PC, PE, and PI + PS) in the heart and bone marrow with the supplementation of DHA-LPC displayed a relatively considerable increase compared with that of EPA supplementation groups. The study provides a reference for the time course of DHA or EPA recovery in phospholipid molecular species in different tissues after the supplementation of EPA-PC, EPA-LPC, and DHA-LPC.

A Comparative Study of the Anti-Obesity Effects of Dietary Sea Cucumber Saponins and Energy Restriction in Response to Weight Loss and Weight Regain in Mice.

Dietary supplementation of sea cucumber saponins and calorie restriction have been proved to be effective in alleviating obesity, but the differences of anti-obesity effects between sea cucumber saponins and energy restriction during weight loss and weight regain are still unknown. In the present study, high-fat-induced obesity mice were randomly divided into three groups, including a high-fat diet group (HF), an energy restriction by 40% group (HF-L), and a sea cucumber saponins group (HF-S), to compare the effects of dietary sea cucumber saponins and energy restriction on the weight, glucose, and lipid metabolism of obese mice during weight loss and weight regain. The results showed that dietary 0.06% sea cucumber saponins and limiting energy intake by 40% had the same weight loss effect. Interestingly, sea cucumber saponins could alleviate impaired glucose tolerance and insulin resistance caused by obesity. In addition, the inhibited SREBP-1c mediated lipogenesis might lead to the alleviation of weight regain after resuming the high-fat diet even when sea cucumber saponins were no longer supplemented. In contrast, limiting energy intake tended to promote lipid synthesis in the liver and white adipose tissue after restoring a high-fat diet, and inflammation was also induced. The findings indicated that sea cucumber saponins could replace calorie restriction to prevent obesity and might be used as a functional food or drug to resist obesity and related diseases caused by obesity.

DHA and EPA Prevent Seizure and Depression-Like Behavior by Inhibiting Ferroptosis and Neuroinflammation via Different Mode-of-Actions in a Pentylenetetrazole-Induced Kindling Model in Mice.

SCOPE: It has been reported that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anticonvulsant effects, yet the respective mechanism of EPA and DHA on epilepsy is still unclarified. This study aims to investigate the effect of EPA and DHA on pentylenetetrazol (PTZ) induced seizures and depression. METHODS AND RESULTS: The administration of EPA and DHA at a dose of 1% w/w significantly inhibits PTZ-induced seizures and depressive-like behavior, whereas EPA outcompetes DHA. Further mechanistic studies reveal that the higher effect of EPA can be partly attributed to the promotion of M2 polarization, inhibition of M1 polarization of microglia, and lower iron content in the brain, resulting from the stronger activation of nuclear factor E2-related factor 2 (Nrf2). This study finds that DHA and EPA comparably inhibit NLRP3 inflammasome activation but with different mode-of-actions: EPA prefers to inhibit the binding of NLRP3 and ASC, while DHA decreases the protein levels of ASC and Caspase-1. CONCLUSIONS: These results indicate that DHA and EPA can efficaciously alleviate PTZ-induced seizure and depressive-like behavior but with different efficiency and molecular mechanisms.

Characterization, stability, digestion and absorption of a nobiletin nanoemulsion using DHA-enriched phosphatidylcholine as an emulsifier in vivo and in vitro.

The emulsification ability of phospholipids might be associated with fatty acid composition. However, there is no research regarding the emulsification ability of marine-derived phospholipids rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The present study developed a nanoemulsion delivery system using DHA-enriched phosphatidylcholine as an emulsifier to deliver the poorly soluble ingredient nobiletin. The prepared nobiletin-loaded nanoemulsion was stable, with a small particle size of approximately 200 nm, a polydispersity index of 0.082, and a neutral zeta potential. The nobiletin-loaded nanoemulsion exhibited high lipolysis ability in in vitro experiments. Moreover, the nobiletin-encapsulated nanoemulsion was digested quickly and entered the serum faster than the oil suspension. There was a high distribution of nobiletin in organs such as the liver, brain, kidney, and spleen in the emulsion group after oral administration for 2 h. The findings provided a nanoemulsion delivery system to increase the bioavailability of nobiletin in vitro and in vivo.

Docosahexaenoic acid-acylated curcumin diester alleviates cisplatin-induced acute kidney injury by regulating the effect of gut microbiota on the lipopolysaccharide- and trimethylamine-N-oxide-mediated PI3K/Akt/NF-κB signaling pathway in mice.

An increasing number of studies have reported the effects of curcumin (Cur) and docosahexaenoic acid (DHA) on alleviating acute kidney injury (AKI). In this work, we have performed a comparative investigation to determine the effect of dietary DHA-acylated Cur esters, ester derivatives of Cur, and recombination of curcumin and DHA on alleviating acute kidney injury in a mouse model induced by a single intraperitoneal injection with cisplatin (20 mg kg-1). The results showed that the DHA-acylated Cur diesters significantly decreased the abnormally increased blood urea nitrogen, creatinine, lipopolysaccharide (LPS) and trimethylamine-N-oxide (TMAO) in serum caused by AKI. Histopathological results confirmed that DHA-acylated Cur diesters clearly reduced the degree of renal tubular injury. The renal protective effect of the DHA-acylated Cur diester was better than that of the monoester and the recombination of Cur and DHA. Notably, we found that the DHA-acylated Cur diester treatment remarkably changed the relative abundance of microbiota related to LPS and TMAO/trimethylamine (TMA) metabolism. Moreover, dietary DHA-acylated Cur diesters clearly reduced the MDA content and elevated GSH levels in the kidney of AKI mice, as well as changed the fatty acid composition in the kidney. Further mechanism studies showed that DHA-acylated Cur diesters significantly inhibited inflammation, apoptosis and oxidative stress by preventing the LPS and TMAO-mediated PI3K/Akt/NF-κB signaling pathway. The above results indicate that DHA-acylated Cur diesters are a potentially novel candidate or targeted dietary pattern to prevent and treat drug-induced acute kidney injury.

Taurine Alleviates Trimethylamine N-Oxide-Induced Atherosclerosis by Regulating Bile Acid Metabolism in ApoE-/- Mice.

Trimethylamine N-oxide (TMAO) widely exists in seafood and is associated with the atherosclerosis progress, but dietary seafood reduced the cardiovascular risk. This intimates that there may be some ingredients in seafood to offset the cardiovascular risk caused by TMAO. Taurine is a marker ingredient in seafood. Thus, this study determined the influences of taurine on TMAO-induced atherosclerosis in apolipoprotein-E-deficient mice. The results showed that dietary taurine significantly reduced the TMAO-induced atherosclerotic lesion area. Further studies found that taurine increased the hepatic- and serum-conjugated bile acid/unconjugated bile acid ratio via increasing hepatic gene expression of conjugated bile acid synthesis. Meanwhile, taurine changed TMAO-induced abnormal bile acid profiles in the gallbladder. Moreover, taurine increased bile acid deconjugation by enhancing the genera Ruminiclostridium level and increased excretion of fecal neutral sterols. Additionally, taurine attenuated inflammation in the serum and artery. These results indicate that taurine alleviated TMAO-induced atherosclerosis via regulating bile acid metabolism.