Alzheimer's disease (AD) is a progressive neurodegenerative disorder with the characteristics of senile plaques, neuroinflammation, neurofibrillary tangles, and destruction of synapse structure stability. Previous studies have verified the protective effects of astaxanthin (AST). However, whether synthesized docosahexaenoic-acid-acylated AST diesters (AST-DHA) could delay AD pathogenesis remains unclear. In the present study, APP/PSEN1 (APP/PS1) double-transgenic mice were administrated with AST and AST-DHA for 2 months. The results of radial 8-arm maze and Morris water maze tests showed that AST-DHA exerted more significant effects than AST in enhancing learning and memory levels of APP/PS1 mice. Further mechanical studies suggested that AST-DHA was superior to AST in regulating the parameters of oxidative stress, reducing tau hyperphosphorylation, suppressing neuroinflammation, and regulating inflammasome expression and activation in APP/PS1 mice. The findings suggested that AST-DHA attenuated cognitive disorders by reducing pathological features in APP/PS1 mice, suggesting that AST-DHA might be a potential therapeutic agent for AD.

The clinical use of glycopeptide antibiotic vancomycin is usually accompanied by nephrotoxicity, limiting its application and therapeutic efficiency. The aim of this study was to investigate the protection of DHA-enriched phosphatidylcholine (DHA-PC) against nephrotoxicity using a model of vancomycin-induced male BALB/c mice with renal injury by measuring death curves, histological changes, and renal function indexes. The addition of DHA in DHA and DHA-PC groups were 300 mg/kg per day on the basis of human intake level in our study. Results indicated that DHA-PC could dramatically extend the survival time of mice, while traditional DHA and PC had no significant effects. Moreover, oral administration of DHA-PC exhibited better effects on reducing vancomycin-induced increases of blood urea nitrogen, creatinine, cystatin C, and kidney injury molecule-1 levels than traditional DHA and PC. DHA-PC significantly delayed the development of vancomycin-induced renal injury, including tubular necrosis, hyaline casts, and tubular degeneration. A further mechanistic study revealed that the protective effect of DHA-PC on vancomycin-mediated toxicity might be attributed to its ability to inhibit oxidative stress and inactivate mitogen-activated protein kinase (MAPK) signaling pathways, which was associated with upregulation of Bcl-2 and downregulation of caspase-9, caspase-3, cytochrome-c, p38, and JNK. These findings suggest that DHA-PC may be acted as the dietary supplements or functional foods against vancomycin-induced nephrotoxicity.

Ethanolamine plasmalogen (pPE), a major phospholipid in neuronal membranes, is specifically reduced in postmortem brains from patients with Alzheimer's disease (AD). The purpose of the present study was to compare the effects of EPA-enriched ethanolamine plasmalogen (EPA-pPE) and EPA-enriched phosphatidylethanolamine (EPA-PE) on cognitive deficiency and illustrate the possible underlying mechanisms. SD rats were divided into four groups including the sham group injected with 0.9% saline and three amyloid-β (Aβ) infusion groups, Aβ42 group, EPA-pPE group and EPA-PE group. EPA-pPE and EPA-PE were administered by gavage (150 mg kg-1 day-1), respectively, once a day for 26 days. Administration of EPA-pPE exerted better effects than EPA-PE in improving Aβ-induced cognitive deficiency in a rat model of Alzheimer's disease. Further mechanical research indicated that EPA-pPE was superior to EPA-PE in regulating oxidative stress via increasing SOD activity and decreasing MDA level, as well as reducing GSK-3β and tau phosphorylation. Moreover, EPA-PE was more effective than EPA-pPE at inhibiting the protein expressions of Bax and caspase 9. The results of neuro-inflammation and inflammasome activation showed that EPA-pPE exerted more significant effects than EPA-PE in inhibiting the expressions of TNF-α and IL-1β, and decreasing NLRP3, pro-caspase 1 and caspase 1 levels. EPA-pPE alleviated Aβ-induced neurotoxicity by inhibiting oxidative stress, neuronal injury, apoptosis and neuro-inflammation, which might depend on the vinyl ether linkage at the sn-1 position.

Neurodegenerative diseases are defined by progressive loss of specific neuronal cell populations and are associated with protein aggregates. Oxidative stress has been implicated in their pathological processes. Previous studies revealed that docosahexaenoic acid (DHA) is beneficial in neurodegenerative diseases. Phospholipids (PLs) derived from marine products are rich in DHA and eicosapentaenoic acid (EPA). In the present study, we investigated the neuroprotective effects of DHA-enriched and unenriched phosphatidylcholine (PC) and phosphatidylserine (PS) on oxidative stress induced by hydrogen peroxide (HO) and tert-butylhydroperoxide in PC12 cells. Cell viability and leakage of lactate dehydrogenase results showed that the neuroprotective effect of PS was superior to that of PC. DHA- and EPA-enriched PC and PS were superior to that without DHA or EPA; in addition, the improvement with n-3 polyunsaturated fatty acid-enriched PS (n-3 PS) was dose dependent. Acridine orange/ethidium bromide staining showed that DHA- and EPA-enriched PS (DHA/EPA-PS) could significantly inhibit apoptosis. Mechanistic studies revealed that EPA-PS and DHA-PS were effective to increase superoxide dismutase (SOD) levels by 48.4 and 58.2 % and total antioxidant capacity (T-AOC) level by 51 and 94 %, respectively, in the HO model. Similar results for SOD and T-AOC levels were shown in the t-BHP model. EPA/DHA-PS could downregulate the messenger RNA level of Caspase-3, Caspase-9, and Bax, upregulate Bcl-2, inhibit Bax, and increase Bcl-2 at protein level. In conclusion, EPA/DHA-PS could protect PC12 cells from oxidative stress and prevent mitochondrial-mediated apoptosis. Our findings indicate that the neuroprotective effects of DHA/EPA-PLs depend on the molecular form. Further studies are necessary to reveal detailed mechanisms and structure-effect relationships.

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 Aβ1–42 peptide to establish an Alzheimer's disease model. Then, the protective effects of Cer against Aβ1–42‐induced cognitive impairment by gavage and feed addition are evaluated. The Morris water maze test results show that oral administration of Cer can significantly ameliorate Aβ1–42‐induced cognitive deficiency at both high dose (200 mg per kg·per day) and low dose (40 mg per kg·per day) for 27 days. Dietary supplement of Cer by feed addition also exhibits the amelioration on the impaired cognitive function. Further findings indicate that Cer ameliorates Aβ1–42‐induced neuronal damage and suppresses the induced apoptosis by decreasing the level of Bax/Bcl‐2. Additionally, Cer enhances the expressions of PSD‐95 and synaptophysin by activating BDNF/TrkB/CREB signaling pathway, thereby ameliorating Aβ1–42‐induced synaptic dysfunction. Furthermore, Cer attenuates Aβ1–42‐induced tau hyperphosphorylation by activating the PI3K/Akt/GSK3β signaling pathway. Conclusion Sea cucumber cerebrosides possess neuroprotective effects against Aβ1–42‐triggered cognitive deficits, which may be a potential nutritional preventive strategy for neurodegenerative diseases.