Study The Lipid-lowering Effect Of Lentinan And Its Molecular Mechanism

Letinous edodes is the common edible fungi in people’s daily life. In China, the output of letinous edodes is ranked the first in the world and letinous edodes is the "mushroom king". Its nutritional components have many physiological functions. Among them, letinous edodes polysaccharide (lentinan) is an important medicinal bioactive substance in letinous edodes. Except for its anti-cancer effects, little study on the lipid-lowering effect in foreign countries, the domestic research in this area is at the initial stage. Until now the molecular mechanism of lentinan on hyperlipidemia, lowering blood lipid is not clear. In this study, we evaluate the lipid-lowering effect lentinan in high fat animal model and explore the molecular mechanism of lentinan on lowering lipid fuction. It provides scientific theoretical basis for development of lentinan-containing functional food and other health products.The effect of lentinan on the phenotype at the macro level of mice. In this study, we established hyperlipidemia mice model to simulate the human high fat diet. The experimental mices were divided into different groups for different treat to evaluate the lipid-lowering effect of lentinan. The experimental results show that letinan can alleviate the body weight of mice in the high fat diet animal model. From the points of view of the shape of liver and their color, the increasing dosage lentinan lowered the increase of liver of high-fat diet. Compared with control group, liver in high-fat diet group is obviously increased, the protective groups especially the 500mg/kg dosage lentinan can attenuate the increased liver caused by high fat diet. In addition, compared to the high fat diet group, liver index were decreased by 0.3%,0.64%, 1.34%, respectively (p>0.05, p<0.05, p<0.01). It suggests that lentinan has certain protective effects on high fat diet induced mice.The effect of lentinan on biochemical phenotype of high-fat diet mice. In order to examine the influence of lentinan on serum lipid levels in mice, biochemical indexes of the serum were analyzed. The results show that letinans can effectively reduce the total cholesterol (TG), total triglyceride (TC), low density lipoprotein (LDL-c), and the effects were dose dependent. And, the effect of the high density lipoprotein (HDL-c) level was the best (p<0.01, p<0.01, p<0.01, p<0.01).The effect of lentinan on the lipid metabolism related genes expressions. Peroxisome proliferator is a member of the nuclear receptor superfamily of the PPARs family, and there are three subtypes, including PPARa, PPARy and PPAR5. In this study, we found that high fat diet results in down-regulated expression of PPARa and PPAR8, upregulated expression of PPARy in liver tissues by Realtime-PCR analysis after RNA extracting, and lentinans amerioate the changed expression with dosage-dependent manner. In addition, Western blotting analysis further confirmed the results. SREBP-1c, a subtype of SREBPs family, is the main transcription factor to regulate gene expression of fatty acid metabolism and glucose metabolism. In this study, we found that the hight fat diet results in the higher expression of SREBP-lc in the liver tissues and lentinans decrease the expression. Besides, western bloting confirmed the data. CD36, a member of the family of class B scavenger receptor SREBPs, is associated with fatty acid transport and reverse cholesterol transport process, which affect the fatty acid content of cells. In this study, compared to the control, high fat diet increased the expression of CD36, and lentinans alleviate the expression. It suggests lentinans will lower lipid through SREBP-lc/CD36 pathway.Glucose metabolism and fat metabolism are affected by high fat diet. Because aggregation of excessive fat will results in inflammatory reaction through the activation of nuclear transcription factor kappa B, and thus cause chronic, low-grade inflammation by metabolism. In this study, the expressions of inflammatory cytokines in the liver tissues were analyzed by Realtime-PCR analysis. The experimental results show that high fat diet increase expression of TNF-a, IL-6 and iNOS. Lentinans treatment significantly decreased the expression levels of proinflammatory factors by real-time quantitively PCR (RT-qPCR) analysis, p<0.01, p<0.01 and p<0.05, respectively. Western blotting further confirmed lentinans inhibit the protein expression levels of TNF-a, IL-6 and iNOS. The results suggest that lentinans can inhibit the expression levels of proinflammatory factors in the high fat diet animal model.In conclusion, this project simulates human diet and established hyperlipemia of ICR mice model. The lipid-lowering effect of lentinan was assessed. Our data showed that lentinan can decrease the body weight of mice in high fat diet animal model, lower the liver index, and decrease the level of TG, TC, LDL-C levels and elevated HDL-C level. The lipid-lowering effect of lentinan is mediated by increasing expression of PPARa, PPAR8 and inhibiting expression of PPARy, SREBP-1c, CD36. While lentinan decrease the expression of the inflammatory factor TNF-a, IL-6 and iNOS. Lentinan can also inhibit chronic inflammation induced by high fat diet in mice.