Ganoderma lucidum polysaccharide peptide alleviates hepatoteatosis via modulating bile acid metabolism dependent on FXR-SHP/FGF

OBJECTIVE Ganoderma lucidum polysaccharide peptide(GLPP)is a group of extract from Ganoderma lucidum with a molecular mass of approximately 5×10^5,which ratio of polysaccharide to peptide is approximately 95%/5%.The purpose of this study was to determine whether GLPP has therapeutic effect on Non-alcoholic fatty liver disease(NAFLD).METHODS Ob/ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD.Key metabolic pathways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting.Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD.RESULTS GLPP administrated for a month alleviated hepatosteatosis,dyslipidemia,liver dysfunction and liver insulin resistance.Pathways of glycerophos⁃pholipid metabolism,fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD.Detection of key enzymes revealed that GLPP reversed low expression of CYP7A1,CYP8B1,FXR,SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice.Besides,GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1c,FAS and ACC via a FXR-SHP dependent mechanism.Additionally,GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepatocytes induced by oleic acid and palmitic acid.CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway,which finally inhibits fatty acid synthesis,indicating that GLPP might be developed as a ther⁃apeutic drug for NAFLD.

Effects of Ganoderma lucidum polysaccharides peptide on tumor metastasis in mice with sleep fragmentation

In recent years,studies have shown that there is a correlation between sleep disorders and cancer,but at the present stage,the research on sleep disorders and tumor related animal models is relatively insufficient.Our research will focus on mice bearing B16F10-luc-G5 melanoma tumor with sleep fragmentation,detecting promoting effect of sleep fragmentation(SF)on the metastasis of melanoma.At the same time,we used Ganoderma lucidum poly⁃saccharides peptide(GL-pp,80 mg·kg-1),a component of traditional Chinese medicine Ganoderma lucidum,which has long enjoyed a good reputation at home and abroad,to observe its anti-tumor metastasis effects on B16F10-luc-G5 mice with SF.Then we used whole proteomics to analyze the difference proteins expressed in lung tissue and compared between groups,includes mice bearing B16F10-luc-G5,mice bearing B16F10-luc-G5 with SF and GL-pp administered mice bearing B16F10-luc-G5 with SF.With the analysis using bioinformatics,we found several key proteins,their genes name are Adcy9,ptk2,Yap1 and Lpin2,Per1 and Tim.And several important clusters,they are,immune system,platelet aggres⁃sion,energy metabolism,cell cytoskeleton,cell adhesion and circadian rhythms.Moreover,we detected the TLR4 signal pathway and macrophage differentiation to reconfirm the results of proteomics and trying to elucidate the mechanism of SF on tumor growth and metastasis and the effects of GL-pp.