Sea cucumbers, belonging to the phylum Echinodermata, have been valued for centuries as a nutritious and functional food with various bioactivities. Sea cucumbers can produce highly active substances, notably saponins, the main secondary metabolites, which are the basis of their chemical defense. The saponins are mostly triterpene glycosides with triterpenes or steroid in aglycone, which possess multiple biological properties including antitumor, hypolipidemic activity, improvement of nonalcoholic fatty liver, inhibition of fat accumulation, antihyperuricemia, promotion of bone marrow hematopoiesis, antihypertension, etc. Sea cucumber saponins have received attention due to their rich sources, low toxicity, high efficiency, and few side effects. This review summarizes current research on the structure and activities of sea cucumber saponins based on the physiological and pharmacological activities from source, experimental models, efficacy, and mechanisms, which may provide a valuable reference for the development of sea cucumber saponins.
Sea cucumber derived sulfated sterols (SS) significantly ameliorated insulin resistance and decreased lipid accumulation compared to plant sterols. Interestingly, our recent study found that intervention with sea cucumber sulfated sterols could significantly increase blood glucose levels of healthy mice in the presence of glucose, while cholesterol sulfate, as one of sulfated sterols, did not have the same effect. However, the exact mechanism of SS on glucose metabolism is still unknown. In the present study, we investigated the potential mechanism by which SS influenced blood glucose homeostasis in healthy mice. Results showed that intervention with sea cucumber sulfated sterols did not affect the levels of hormones related to glucose metabolism, while led to a significant decrease in the synthesis of liver glycogen and muscle glycogen. Besides, the expression of proteins associated with the promotion of gluconeogenesis dramatically increased in the mice intervened with sea cucumber sulfated sterols. These findings suggested that sea cucumber sulfated sterols might change blood glucose metabolism in healthy mice by reducing glycogenesis and promoting gluconeogenesis.
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.
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 β-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.
A lack of n-3 polyunsaturated fatty acids (PUFAs) in mothers' diet significantly reduced the amount of docosahexaenoic acid (DHA) in the brains of offspring, which might affect their brain function. Our previous research has proven multiple benefits of eicosapentaenoic acid (EPA)-enriched ethanolamine plasmalogen (pPE) in enhancing the learning and memory ability. However, the effect of dietary supplementation with EPA-pPE on the DHA content in the brain and liver of offspring lacking n-3 PUFAs in early life is still unclear. Female ICR mice were fed with n-3 PUFA-deficient diets throughout the gestation and lactation periods to get n-3 PUFA-deficient offspring. The lipid profiles in the cerebral cortex and liver of offspring were analyzed using lipidomics after dietary supplementation with EPA-pPE (0.05%, w/w) and EPA-phosphatidylcholine (PC) (0.05%, w/w) for 2 weeks after weaning. Dietary supplementation with EPA could significantly change fatty acid composition in a variety of phospholipid molecular species compared with the n-3 deficient group. EPA-pPE and EPA-PC remarkably increased the DHA content in the brain PC, ether-linked phosphatidylcholine (ePC), and phosphatidylethanolamine plasmalogen (pPE) and liver triglyceride (TG), lyso-phosphatidylcholine (LPC), ePC, phosphatidylethanolamine (PE), and pPE molecular species, in which EPA-pPE showed more significant effects on the increase of DHA in cerebral cortex PC, ePC and liver PC compared with EPA-PC. Both EPA-phospholipids could effectively increase the DHA levels, and the pPE form was superior to PC in the contribution of DHA content in the cerebral cortex PC, ePC and liver PC molecular species. EPA-enriched ethanolamine plasmalogen might be a good nutritional supplement to increase DHA levels in the brains of n-3 PUFA-deficient offspring.
Cisplatin is one of the most effective chemotherapeutic agents used for the treatment of a wide variety of cancers. However, cisplatin has been associated with nephrotoxicity, which limits its application in clinical treatment. Various studies have indicated the protective effect of phospholipids against acute kidney injury. However, no study has focused on the different effects of phospholipids with different fatty acids on cisplatin-induced nephrotoxicity and on the combined effects of phospholipids and cisplatin in tumour-bearing mice. In the present study, the potential renoprotective effects of phospholipids with different fatty acids against cisplatin-induced nephrotoxicity were investigated by determining the serum biochemical index, renal histopathological changes, protein expression level and oxidative stress. The results showed that docosahexaenoic acid-enriched phospholipids (DHA-PL) and eicosapentaenoic acid-enriched phospholipids (EPA-PL) could alleviate cisplatin-induced nephrotoxicity by regulating the caspase signaling pathway, the SIRT1/PGC1α pathway, and the MAPK (mitogen-activated protein kinase) signaling pathway and by inhibiting oxidative stress. In particular, DHA-PL exhibited a better inhibitory effect on oxidative stress and apoptosis compared to EPA-PL. Furthermore, DHA-PL exhibited an additional effect with cisplatin on the survival of ascitic tumor-bearing mice. These findings suggested that DHA-PL are one kind of promising supplement for the alleviation of cisplatin-induced nephrotoxicity without compromising its antitumor activity.
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.
Alpha-linolenic acid (ALA) is capable of synthesizing EPA and DHA in vivo, but the conversion rate is hard to meet the body's need for rapid DHA supplementation. Studies have shown that fucoxanthin can increase DHA content in the liver of mice, but the mechanism is not clear. Moreover, the effect of fucoxanthin and its metabolite fucoxanthinol on the chain lengthening reaction of n-6 polyunsaturated fatty acids (PUFAs) is little studied. In this study, the effects of fucoxanthin and fucoxanthinol on the chain elongation of n-3 and n-6 series PUFAs were investigated in mice. Results showed that fucoxanthin and fucoxanthinol significantly increased the conversion of n-3 series ALA to DHA and n-6 series LA to AA in the serum, liver, small intestine, and heart of mice. In addition, fucoxanthin accelerated the rate of DHA supplementation by ALA in the brain. Further mechanistic studies revealed that the role of fucoxanthin in promoting PUFAs conversion was not regulated at transcriptional level, but by increasing the activity of fatty acid desaturase 2 (FADS2), a key enzyme of chain elongation reaction of n-3 and n-6 PUFAs. This study fundamentally provided theoretical bases for a new strategy of dietary supplementation of n-3 and n-6 PUFAs.
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