Preparation of Ganoderma lucidum polysaccharide‑chromium (III) complex and its hypoglycemic and hypolipidemic activities in high-fat and high-fructose diet-induced pre-diabetic mice.

Polysaccharide from Ganoderma lucidum 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 G. lucidum polysaccharide‑chromium (III) [GLP-Cr(III)] complex. Response surface methodology (RSM) was used to optimize the reaction conditions for the maximum chelation rate of GLP-Cr(III) complex. The optimal reaction conditions obtained from RSM were as follows: concentration of CrCl3 5.71 mg/mL, pH 6.36, temperature 66.4 °C and time 2.0 h, respectively. The pH was the most significant factor, followed by reaction temperature and CrCl3 concentration. Under the optimal conditions, the experimental chelation rate was 94.17 ± 1.0% for GLP-Cr(III) complex, which agreed closely with the predicted value (94.60%). Fourier transform infrared (FT-IR) spectroscopy revealed that the primary sites of chromium (III)-binding in G. lucidum polysaccharide were OH and CO groups, which induce the morphology change from flat sheet to rough surface. Meanwhile, according to the result of X-ray diffraction (XRD), the crystal degree of GLP was disappeared after chelation with Cr(III). The presence of a "blind zone" in the 1H NMR spectrum obviously indicated the binding of Cr(III) to GLP. Additionally, the effects of GLP-Cr(III) complex on hyperglycemia and hyperlipidemia in high fructose and fat diet-induced pre-diabetic mice were also investigated. Results showed that the serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting blood glucose levels and glucose tolerance in mice supplemented with GLP-Cr(III) complex (50 mg/kg day) were significantly lower than the model group (P < 0.01). More importantly, the GLP-Cr(III) complex had no significant adverse effects on the physiological metabolism, organ index, and liver tissue morphology of mice fed a normal diet. These results suggest that GLP-Cr(III) complex could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.

Li L ，Xu JX ，Cao YJ ，Lin YC ，Guo WL ，Liu JY ，Bai WD ，Zhang YY ，Ni L ，Liu B ，Rao PF ，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 ... -  《-》

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 ... -  《-》

Organic chromium derived from the chelation of Ganoderma lucidum polysaccharide and chromium (III) alleviates metabolic syndromes and intestinal microbiota dysbiosis induced by high-fat and high-fructose diet.

Organic chromium is of great interest and has become an important chromium supplement resource in recent years because of its low toxicity and easy absorption. In our previous study, we synthesized a novel organic chromium [GLP-Cr] through the chelation of Ganoderma lucidum polysaccharide and chromium (III). The purpose of this study was to investigate the beneficial effects of GLP-Cr on the improvement of metabolic syndromes (MetS) in mice fed with a high-fat and high-fructose diet (HFHFD) and its mechanism of action. The results indicated that oral administration of GLP-Cr inhibited the excessive exaltation of body weight, glucose tolerance, fasting blood glucose and lipid levels, hepatic total cholesterol (TC), triglyceride (TG) levels caused by HFHFD. Besides, 16S rRNA amplicon sequencing showed that GLP-Cr intervention evidently ameliorated intestinal microbiota dysbiosis by changing the proportions of some intestinal microbial phylotypes. In addition, correlation network-based analysis indicated that the key intestinal microbial phylotypes were closely related to biochemical parameters associated with MetS under GLP-Cr intervention. Liver metabolomics analysis suggested that GLP-Cr intervention significantly regulated the levels of some biomarkers involved in alpha-linolenic acid metabolism, fatty acid biosynthesis, steroid hormone biosynthesis, glycerophospholipid metabolism, glycerolipid metabolism, steroid hormone biosynthesis, primary bile acid biosynthesis, and so on. Moreover, GLP-Cr intervention regulated liver mRNA levels of key genes associated with glucose and lipid metabolism. The mRNA level of glucose transporter type 4 (Glut4) was markedly increased by GLP-Cr intervention, and the mRNA levels of phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6Pase) in the liver were significantly decreased. Meanwhile, GLP-Cr intervention significantly decreased hepatic mRNA levels of cluster of differentiation 36 (Cd36), acetyl-CoA carboxylase 1 (Acc1) and sterol regulatory element binding protein-1c (Srebp-1c), indicating that GLP-Cr intervention inhibited the excessive accumulation of free fatty acids in the liver. These findings suggest that the prevention of hyperglycemia and dyslipidemia by GLP-Cr may be closely related to the regulation of gut microbial composition and hepatic metabolic pathways, thus GLP-Cr can be serving as a functional component in the prevention of MetS.

Lv XC ，Wu Q ，Yuan YJ ，Li L ，Guo WL ，Lin XB ，Huang ZR ，Rao PF ，Ai LZ ，Ni L ... -  《-》

Characterization, hypolipidemic and antioxidant activities of degraded polysaccharides from Ganoderma lucidum.

The aim of this work is to characterize the primary structure and physicochemical properties of natural polysaccharides (GLP) and degraded polysaccharides (GLPUD) from Ganoderma lucidum, and evaluate their hypolipidemic and antioxidant activities. The results of particle size distribution and scanning electron microscopy (SEM) showed that Ganoderma lucidum polysaccharides were effectively degraded by ultrasonic method. GLPUD was composed of the same monosaccharide units as GLP but with different molar ratios. Infrared spectra and NMR showed that the primary structure of polysaccharides had not been changed by ultrasonic degradation. Meanwhile, the thermal stability of polysaccharides increased after ultrasonic treatment. After administration by GLP and GLPUD four weeks, body weight, visceral index, atherosclerosis index (AI) and biochemical indicators in serum and in liver were determined. The results showed that GLPUD had stronger hypolipidemic and antioxidant activities than GLP. GLPUD was more effective than the GLP for reducing AI, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), raising high density lipoprotein (HDL-C) (p < 0.01), reducing malondialdehyde (MDA) content, as well as increasing the glutathione peroxidase (GSH-Px) in mice serum, increasing superoxide dismutase (SOD) activity and reducing MDA content in liver (p < 0.05 or p < 0.01). In addition, the histopathological observations of mice livers showed that GLPUD could significantly improve lipid metabolism disorder in hepatocytes. Thus, GLPUD might be tested as a more effective hypolipidemic drug.

Xu Y ，Zhang X ，Yan XH ，Zhang JL ，Wang LY ，Xue H ，Jiang GC ，Ma XT ，Liu XJ ... -  《-》