Hypoglycemic and hypolipidemic activities of Grifola frondosa polysaccharides and their relationships with the modulation of intestinal microflora in diabetic mice induced by high-fat diet and streptozotocin.

This study aimed to investigate the hypoglycemic and hypolipidemic activities of polysaccharides from Grifola frondosa (GFP) in diabetic mice induced by high-fat diet (HFD) and streptozotocin (STZ). Results showed that oral administration of GFP markedly reduced the serum levels of fasting blood glucose (FBG), oral glucose tolerance (OGT), cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and significantly decreased the hepatic levels of TC, TG and free fatty acids (FFA). Meanwhile, high-dose of GFP supplementation (900 mg/kg day) also showed powerful effects on moderating the composition of intestinal microflora in diabetic mice, especially altering the functionally relevant intestinal microbial phylotypes. Spearman's correlation network analysis revealed that key microbial phylotypes responding to GFP intervention were strongly correlated with the glucose and lipid metabolic disorders associated parameters. Moreover, GFP treatment regulated mRNA expression levels of the genes responsible for hepatic glucose and lipid metabolism. It is noteworthy that GFP treatment markedly increased mRNA expression of cholesterol 7α-hydroxylase (CYP7A1) and bile salt export pump (BSEP), suggesting an enhancement of bile acids (BAs) synthesis and excretion in liver. These findings demonstrated that GFP could prevent hyperglycemia and hyperlipidemia in diabetic mice by altering gut microbiota and regulating hepatic glycolipid metabolism related genes, and therefore could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.

Guo WL ，Deng JC ，Pan YY ，Xu JX ，Hong JL ，Shi FF ，Liu GL ，Qian M ，Bai WD ，Zhang W ，Liu B ，Zhang YY ，Luo PJ ，Ni L ，Rao PF ，Lv XC ... -  《-》

Hypoglycemic and hypolipidemic mechanism of organic chromium derived from chelation of Grifola frondosa polysaccharide-chromium (III) and its modulation of intestinal microflora in high fat-diet and STZ-induced diabetic mice.

Polysaccharide from Grifola frondosa is an excellent metal-ion chelating agent owing to its distinctive structure and outstanding functional activities. Our previous research has successfully synthesized novel organic chromium derived from the chelation ofG. frondosapolysaccharide-chromium (III) [GFP-Cr(III)]. The purpose of present research was to reveal the hypoglycemic and hypolipidemic mechanism of GFP-Cr(III), and its relationship with the modulation of intestinal microflora. Successful fabrication of GFP-Cr(III) was verified by thermogravimetric analysis (TGA), powder X-ray diffraction (XRD) and 1H NMR spectrum.The hypoglycemic and hypolipidemic effects were examined using type 2 diabetic mice induced by a high-fat diet (HFD) and streptozocin (STZ). Results indicated that GFP-Cr(III) intervention improved abnormal serum biochemical indicators (triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and glucose), inhibited lipid accumulation and steatosis in the liver. Metagenomic analysis revealed that GFP-Cr(III) treatment produced obvious changes on the intestinal microflora in T2DM mice. Thecorrelationnetwork analysis further revealed that the serum and hepatic lipid profiles were positively correlated with Streptococcus and Enterococcus, but negatively correlated with Enterorhabdus, Ruminococcaceae-UCG-011, Coriobacteriaceae and Micrococcaceae. Meanwhile, oral administration with GFP-Cr(III) regulated the mRNA expression related to glucose and lipid metabolism. These results of present study suggest that GFP-Cr(III) could be used as potential functional food ingredients for the amelioration of hyperglycemia and hyperlipidemia.

Guo WL ，Chen M ，Pan WL ，Zhang Q ，Xu JX ，Lin YC ，Li L ，Liu B ，Bai WD ，Zhang YY ，Ni L ，Rao PF ，Lv XC ... -  《-》

Grifola frondosa polysaccharides ameliorate lipid metabolic disorders and gut microbiota dysbiosis in high-fat diet fed rats.

Li L ，Guo WL ，Zhang W ，Xu JX ，Qian M ，Bai WD ，Zhang YY ，Rao PF ，Ni L ，Lv XC ... -  《-》

Preparation of a novel Grifola frondosa polysaccharide-chromium (III) complex and its hypoglycemic and hypolipidemic activities in high fat diet and streptozotocin-induced diabetic mice.

Polysaccharide from Grifola frondosa is one of the best metal-ion chelating agents because of its structural characteristics and excellent functional activities. In this study, we synthesized and characterized a novel Grifola frondosa polysaccharide-chromium (III) [GFP-Cr(III)] complex. Response surface methodology (RSM) was used to optimize the reaction conditions for the maximum chelation rate of GFP-Cr(III) complex. The optimal reaction conditions obtained from RSM were as follows: concentration of CrCl3 6.97 mg/mL, pH 7.75 and temperature 71.73 °C, respectively. The pH was the most significant factor, followed by reaction temperature and concentration of CrCl3. Under the deduced optimal conditions (CrCl3 7.0 mg/mL, pH 7.7 and temperature 70.0 °C), the experimental chelation rate was 28.01% ± 0.18% for GFP-Cr(III) complex, which agreed closely with the predicted value (27.61%). Fourier transform infrared (FTIR) spectroscopy revealed that the primary sites of chromium (III)-binding in polysaccharides were OH and CN groups, leading to the structure of GFP-Cr(III) complex was loose than the original polysaccharide. Nevertheless, Cr(III) did not make a fundamental change in the structure of GFP when comparing the FTIR spectra of GFP and GFP-Cr(III) complex. Additionally, the effects of GFP-Cr(III) complex on hyperglycemia and hyperlipidemia in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were also investigated. Results showed that the serum total cholesterol (TC), total triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting blood glucose levels and glucose tolerance in diabetic mice fed a high-fat diet (HFD) supplemented with GFP-Cr(III) complex (900 mg/kg day) were significantly lower than the diabetic group (P < 0.01). These results suggest that GFP-Cr(III) complex could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.

Guo WL ，Shi FF ，Li L ，Xu JX ，Chen M ，Wu L ，Hong JL ，Qian M ，Bai WD ，Liu B ，Zhang YY ，Ni L ，Rao PF ，Lv XC ... -  《-》

Regulatory effect of Grifola frondosa extract rich in polysaccharides and organic acids on glycolipid metabolism and gut microbiota in rats.

The present study investigated the composition of water extract of Grifola frondosa (GFWE) and its regulatory effects on glycolipid metabolism and gut microbiota in rats. Structural characteristics of GFWE were detected by high performance liquid chromatography and ultra-high-performance liquid chromatography with mass spectrometry. The hypoglycemic and hypolipidemic activities of GFWE were obtained by inhibition of weight gain, recovery of serum glucose and lipid, and reverse of liver tissue damage. GFWE has up-regulated the relative mRNA and protein expression levels of adenine monophosphate activated protein kinase-α, peroxisome proliferator-activated receptors-α, and glucokinase, while down-regulated sterol regulatory element-binding transcription factor-1c and acetyl CoA carboxylase. Moreover, GFWE increased the abundances of caecal bacteria Oscillibacter and Barnesiella, which showed a significant negative correlation with serum glucose and lipid parameters. And GFWE enhanced the levels of total bile acids and short-chain fatty acids in the cecum. These results indicated that GFWE could be provided as a potential candidate to regulate glycolipid metabolism and gut microbiota.

Pan Y ，Wan X ，Zeng F ，Zhong R ，Guo W ，Lv XC ，Zhao C ，Liu B ... -  《-》