Study On Effects And Mechanism Of Saponins Of Sea Cucumber On Lipid Metabolism

Saponin is a dominating secondary metabolite of sea cucumber, which has been suggested to be responsible for beneficial effects of sea cucumber. It has been proven that saponins of sea cucumber (SSC) exhibit a variety of bioactivities, such as antifungal, anti-tumor and immunomodulatory effects. However there are few reports about its potential effect on lipid metabolism. The present study investigated the regulatory effects of SSC on lipid metabolism and its molecular mechanism, especially in nonalcoholic fatty liver (NAFLD) model and obesity model.Sea cucumber contains various bioactive compounds, such as saponins, polysaccharides, glycolipids, collagens and so on. Most of the current researches focused on the whole body of sea cucumber, and little information was known on the respective function of those bioactive components. Therefore the first study was undertaken to compare the difference in improving lipid metabolism, among saponins, polysaccharides, collagen peptides, dregs and residues without saponin. The results indicated that saponins and polysaccharides could suppress adipose accumulation, reduce serum and hepatic lipids in rats. Both of them are the main lipid-lowering components in sea cucumber, but saponins were more effective than polysaccharides. In view of these results, the possible mechanism by which saponins improve lipid metabolism was investigated. The results showed that SSC inhibited pancreatic lipase activity in vitro, thereby suppressed the digestion and absorption of fat. Otherwise, SSC was found to decrease activities of FAS and SCD, suggesting that it could impair endogenous lipid synthesis.A further study was undertaken to examine the effect of SSC on the preventive activity of NAFLD. The study using an orotic acid-induce fatty liver model, indicated that SSC significantly alleviated hepatic steatosis and reduced serum TG level in a dose-independent manner. To clarify the molecule mechanism by which SSC alters hepatic lipid metabolism, we examined two pathways related in fatty acid biosynthesis andβ-oxidation. The data showed that hepatic lipogenic enzymes, like FAS, ME and G6PDH were significantly inhibited by SSC treatment. And mRNA expression of those enzymes and its transcription regulatory factor SREBP-1c showed the same trend with the enzyme activity. Besides SSC also stimulated CPT activity, which is the critical enzyme involved in fatty acidβ-oxidation. The gene expression of PPARα, together with its response genes, CPT-1, CPT-2 and ACO were upregulated by Realtime-PCR detection. Additional work was done to examine the possible mechanism of SSC improving cholesterol metabolism. The results indicated SSC could inhibit the gene expression of SREBP-2 and HMG-CoA reductase, but did not influence LDL receptor expression. In view of these results, we got a conclusion that SSC may prevent the development of NAFLD. The molecular mechanism for alleviating NAFLD is partly result from negative regulation of SREBP-1c-mediated lipogenesis. On the other hand, reduced hepatic TG accumulation was associated with the enhancement of PPARa-mediatedβ-oxidation. In addition, the suppression of cholesterol synthesis may also contribute to the reduction of hepatic steatosis.Finally we evaluated the antiobesity effect of SSC and its potential activity on preventing type 2 diabetes, comparing with saponins of Ginseng (SG). The influence of SSC and SG on body weight gain, makers of hepatic steatosis and insulin resistance were determined in the high fat diet-induced mouse model for obesity and IR. Our findings demonstrated that SSC significantly suppressed body weight gain and adipose tissue weight, reduced serum and hepatic lipids, showing an excellent antiobesity effect. Serum adiponectin level was observed much higher in SSC group by ELASA detection, suggesting that the lipid-lowering effect of SSC may be due to the adiponcetin activated AMPK signal pathway and PPARa-mediated fatty acid P-oxidation. Additionally, SSC improved glucose tolerance obviously using an oral glucose tolerance test, with a reduction of serum insulin. The results indicated that SSC improved insulin sensitivity and consequently prevent type 2 diabetes.To our knowledge, this is the first report on the lipid-lowering effect of saponins extracted from sea cucumber. The present study enriched the sea cucumber research field, provided scientific basis for its exploitation and utilization. The findings also provided evidence that SSC is a safe and effective natural product which could improve lipid metabolism; it can be used as dietary supplement to prevent diseases caused by lipid metabolism disorder, like hyperlipidemia, NAFLD, obesity and insulin resistance and so on.