Sea cucumber-derived compounds for treatment of dyslipidemia: A review

Abstract

Dyslipidemias are disorders of plasma levels of lipids, such as elevated levels of total cholesterol and triglyceride, that are associated with various human diseases including cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Statins are the first-line drugs for treatment of dyslipidemia. However, a substantial proportion of patients cannot reach the recommended LDL-c level even with the highest tolerated doses of statins, and there is no available drug specifically for NAFLD therapy. Sea cucumbers are one of the widely distributed invertebrates, and are an important resource of food and medicine. Sea cucumbers have many valuable nutrients including saponins, fatty acids, phospholipids, cerebrosides, sulfated polysaccharides, as well as proteins and peptides. In recent years, these natural products derived from sea cucumbers have attracted attentions for treatment of CVD and NAFLD because of their lipid-lowering effect and low toxicity. However, the hypolipidemic mechanisms of action and the structure-activity relationship of these bioactive components have not been well-documented in literature. This review article summarizes the signaling pathways and the potential structure-activity relationship of sea cucumber-derived bioactive compounds including saponins, lipids, carbohydrates as well as peptides and proteins. This article will provide information useful for the development of sea cucumber-derived lipid-lowering compounds as well as for investigation of hypolipidemic compounds that are derived from other natural resources.

Natural products in atherosclerosis therapy by targeting PPARs: a review focusing on lipid metabolism and inflammation

“…Sea cucumber saponins reduce lipogenesis and promote fatty acid β-oxidation via inhibiting SREBP-1c and enhancing the expression of PPARα and ACOX1, respectively, thereby improving lipid deposition in rodents ( 134 – 137 ). In combination with eicosapentaenoic acid-enriched phospholipids, sea cucumber saponins further reduce hepatic TG partially by enhancing the expression of PPARα as reviewed by Lin et al ( 137 ).…”

“…In combination with eicosapentaenoic acid-enriched phospholipids, sea cucumber saponins further reduce hepatic TG partially by enhancing the expression of PPARα as reviewed by Lin et al ( 137 ). Interestingly, sea cucumber saponin treatment induces changes of lipid metabolism-related genes including PPARα in rhythm, suggesting saponin may modulate lipid metabolism by regulating the clock genes, such as CLOCK and BMAL1 ( 137 , 138 ). The major bioactive component of saponin, echinoside A, also regulates the expression of some key genes that are involved in lipid metabolism in a diurnal manner ( 139 ).…”

“…Polysaccharides are a kind of carbohydrate polymers that are generally consisted of more than ten monosaccharides through glycosidic linkages in linear or branched chains. Given polysaccharides generally have low toxicity and various biological activities, such as antioxidant, anti-inflammatory, and anti-atherosclerosis, some polysaccharides have been used in medical and biochemical areas as reviewed by different groups ( 137 , 167 – 169 ). Notably, carbohydrates are found to exert their function via activating PPAR signaling pathways ( Figure 7 ).…”

“…Besides brown seaweeds, sea cucumber-derived polysaccharides improve lipid metabolism in different models ( 137 ). For instance, Isostihopus badionotus -derived fucosylated chondroitin sulfate (4,300 Da) exhibits a hypolipidemic effect in mice partially by down-regulating the expression of FAS and PPARγ ( 175 ).…”

Saponins of North Atlantic Sea Cucumber: Chemistry, Health Benefits, and Future Prospectives

“…In general terms, saponins are the primary secondary metabolites of sea cucumbers, which are the basis of their chemical defense. Studies have reported that saponins extracted from sea cucumber show biological properties including antitumor [ 36 ], anti-obesity [ 37 ], anti-fungal, anti-bacterial [ 38 ], and anti-hyperuricemic activities and immune-modulatory activities [ 39 ]. Based on these impressive properties, several studies have isolated, analyzed, and characterized saponins from different organisms [ 1 , 6 , 8 , 10 , 13 , 40 , 41 ].…”