ABSTRACT
In recent years, organic chromium (III) supplements have received increasing attentions for their low toxicity, high bioavailability and wide range of health-promoting benefits. This study aimed to investigate the preventive effects of chromium (III)-enriched yeast (YCr) on high-fat and high-fructose diet (HFHFD)-induced hyperlipidemia and hyperglycemia in mice, and further clarify its mechanism of action from the perspective of intestinal microbiomics and liver metabolomics. The results indicated that oral administration of YCr remarkably inhibited the aberrant elevations of body weight, blood glucose and lipid levels, hepatic cholesterol (TC) and triglyceride (TG) levels caused by HFHFD. Liver histological examination showed that oral YCr intervention inhibited HFHFD induced liver lipid accumulation. Besides, 16S rDNA amplicon sequencing showed that YCr intervention was beneficial to ameliorating intestinal microbiota dysbiosis by altering the proportion of some intestinal microbial phylotypes. Correlation-based network analysis indicated that the key intestinal microbial phylotypes intervened by YCr were closely related to some biochemical parameters associated with glucose and lipid metabolism. Liver metabolomics analysis revealed that dietary YCr intervention significantly regulated the levels of some biomarkers involved in purine metabolism, glycerophospholipid metabolism, citrate cycle, pyrimidine metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and so on. Moreover, dietary YCr intervention regulated the mRNA levels of key genes associated with glucose, cholesterol, fatty acids and bile acids metabolism in liver. These findings suggest that dietary YCr intervention has beneficial effects on glucose and lipid metabolism by regulating intestinal microbiota and liver metabolic pathway, and thus can be served as a functional component to prevent hyperlipidemia and hyperglycemia.
ABSTRACT
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.
Subject(s)
Gastrointestinal Microbiome , Metabolic Syndrome , Reishi , Acetyl-CoA Carboxylase/genetics , Acetyl-CoA Carboxylase/metabolism , Acetyl-CoA Carboxylase/pharmacology , Animals , Bile Acids and Salts/pharmacology , Biomarkers , Blood Glucose/metabolism , Cholesterol , Chromium/chemistry , Diet , Diet, High-Fat/adverse effects , Dysbiosis/drug therapy , Fatty Acids, Nonesterified , Fructose/adverse effects , Glucose/metabolism , Glucose Transporter Type 4 , Glucose-6-Phosphatase/metabolism , Glucose-6-Phosphatase/pharmacology , Glycerophospholipids , Hormones , Metabolic Syndrome/drug therapy , Metabolic Syndrome/etiology , Mice , Phosphoenolpyruvate/pharmacology , Polysaccharides/pharmacology , RNA, Messenger/metabolism , RNA, Ribosomal, 16S , Reishi/genetics , Steroids/pharmacology , Sterol Regulatory Element Binding Protein 1/metabolism , Triglycerides , alpha-Linolenic Acid/pharmacologyABSTRACT
Alcoholic liver injury is mainly caused by long-term excessive alcohol consumption and has become a global public threat to human health. It is well known that Ganoderma lucidum has excellent beneficial effects on liver function and lipid metabolism. The object of this study was to investigate the hepatoprotective effects of ganoderic acid A (GAA, one of the main triterpenoids in G. lucidum) against alcohol-induced liver injury and reveal the underlying mechanisms of its protective effects. The results showed that oral administration of GAA significantly inhibited the abnormal elevation of the liver index, serum total triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in mice exposed to alcohol intake, and also significantly protected the liver against alcohol-induced excessive lipid accumulation and pathological changes. Besides, alcohol-induced oxidative stress in the liver was significantly ameliorated by the dietary intervention of GAA through decreasing the hepatic levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA), and increasing hepatic activities of catalase (CAT), superoxide dismutase (SOD), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and hepatic levels of glutathione (GSH). In addition, GAA intervention evidently ameliorated intestinal microbial disorder by markedly increasing the abundance of Muribaculaceae, Prevotellaceae, Jeotgalicoccus, Bilophila, Family_XIII_UCG_001, Aerococcus, Ruminococcaceae_UCG_005, Harryflintia, Christensenellaceae, Rumonpcpccaceae, Prevotelaceae_UCG_001, Clostridiales_vadinBB60_group, Parasutterella and Bifidobacterium, but decreasing the proportion of Lactobacillus, Burkholderia_Caballeroria_Paraburkholderia, Escherichia_Shigella and Erysipelatoclostridium. Furthermore, liver metabolomics based on UPLC-QTOF/MS demonstrated that oral administration of GAA had a significant regulatory effect on the composition of liver metabolites in mice exposed to alcohol intake, especially the levels of the biomarkers involved in the metabolic pathways of riboflavin metabolism, glycine, serine and threonine metabolism, pyruvate metabolism, glycolysis/gluconeogenesis, biosynthesis of unsaturated fatty acids, synthesis and degradation of ketone bodies, fructose and mannose metabolism. Moreover, dietary supplementation of GAA significantly regulated the hepatic mRNA levels of lipid metabolism and inflammatory response related genes. Conclusively, these findings demonstrate that GAA has beneficial effects on alleviating alcohol-induced liver injury and is expected to become a new functional food ingredient for the prevention of alcoholic liver injury.
Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Reishi , Animals , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Cholesterol/metabolism , Ethanol/pharmacology , Heptanoic Acids , Lanosterol/analogs & derivatives , Lanosterol/pharmacology , Lipid Metabolism , Liver/metabolism , Mice , Oxidative StressABSTRACT
Alcoholic liver injury is mainly caused by excessive alcohol consumption and has become a global public health problem threatening human health. It is well known that Ganoderma lucidum possesses various excellent beneficial effects on liver function and lipid metabolism. The purpose of this study was to evaluate the underlying protective effect and action mechanism of ganoderic acids-rich G. lucidum ethanol extract (GLE) on alcohol-induced liver injury in mice with excessive alcohol intake. Results showed that oral administration of GLE could obviously inhibit the abnormal increases of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and also significantly protect the liver against alcohol-induced excessive hepatic lipid accumulation and pathological changes. In addition, alcohol-induced oxidative stress in liver was significantly ameliorated by the dietary intervention of GLE through reducing the hepatic levels of maleic dialdehyde (MDA) and lactate dehydrogenase (LDH), and increasing the hepatic levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and alcohol dehydrogenase (ADH). Compared with the model group, GLE intervention significantly ameliorated the intestinal microbial disorder by elevating the relative abundance of Ruminiclostridium_9, Prevotellaceae_UCG-001, Oscillibacter, [Eubacterium]_xylanophilum_group, norank_f_Clostridiates_vadinBB60_group, GCA-900066225, Bilophila, Ruminococcaceae_UCG-009, norank_f_Desulfovibrionaceae and Hydrogenoanaerobacterium, but decreasing the proportion of Clostridium_sensu_stricto_1. Furthermore, liver metabolomic profiling suggested that GLE intervention had a significant regulatory effect on the composition of liver metabolites in mice with excessive alcohol intake, especially the levels of some biomarkers involved in primary bile acid biosynthesis, riboflavin metabolism, tryptophan metabolism, biosynthesis of unsaturated fatty acids, fructose and mannose metabolism, glycolysis/gluconeogenesis. Additionally, dietary supplementation with GLE significantly regulated the mRNA levels of key genes related to fatty acids metabolism, ethanol catabolism and inflammatory response in liver. Conclusively, these findings indicate that GLE has a potentially beneficial effect on alleviating alcohol-induced liver injury and may be developed as a promising functional food ingredient.
ABSTRACT
Lactobacillus paracasei FZU103, a probiotic previously isolated from the traditional brewing process of Hongqu rice wine, may have the beneficial effect of improving the disorder of lipid metabolism. This study aimed to determine the beneficial effects of L. paracasei FZU103 on improving hepatic lipid accumulation associated with hyperlipidemia. Results indicated that L. paracasei FZU103 intervention significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, ameliorated the biochemical parameters of serum and liver related to lipid metabolism in HFD-fed mice. Histological analysis also showed that the excessive accumulation oflipid dropletsin the livers induced by HFD-feeding was greatly alleviated by L. paracasei FZU103 intervention. In addition, L. paracasei FZU103 also promoted the excretion of bile acids (BAs) through feces. Metagenomic analysis revealed that oral supplementation with L. paracasei FZU103 significantly increased the relative abundance of Ruminococcus, Alistipes, Pseudoflavonifractor and Helicobacter, but decreased the levels of Blautia, Staphylococcos and Tannerella in HFD-fed mice. The relationships between lipid metabolic parameters and intestinal microbial phylotypes were also revealed by correlation heatmap and network. Furthermore, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics demonstrated that L. paracasei FZU103 had a significant regulatory effect on the metabolic pathways of glycerophospholipid metabolism, fatty acid degradation, fatty acid elongation, unsaturated fatty acids biosynthesis, riboflavin metabolism, glycerolipid metabolism, primary bile acid biosynthesis, arachidonic acid metabolism, etc. Additionally, L. paracasei FZU103 intervention regulated expression of hepatic genes involved in lipid metabolism and bile acid homeostasis, and promoted fecal excretion of intestinal BAs. These findings present new evidence supporting that L. paracasei FZU103 has the potential to improve lipid metabolism, and could be used as a potential functional food for the prevention of hyperlipidemia.
Subject(s)
Gastrointestinal Microbiome , Hyperlipidemias , Lacticaseibacillus paracasei , Animals , Diet, High-Fat , Hyperlipidemias/prevention & control , Lipid Metabolism , MiceABSTRACT
Monascus-fermented rice has been used to treat digestive disorder and promote blood circulation in China and other Asian countries for centuries. However, the effects and mechanisms of Monascus purpureus-fermented common buckwheat (HQ) on non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are unclear. Here, oral supplementation of HQ significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, ameliorated some biochemical parameters of serum and liver related to lipid metabolism in mice fed a high-fat and high-cholesterol diet (HFD). Histological analysis also showed that the excessive accumulation of lipid droplets in the livers induced by HFD-feeding was greatly alleviated by HQ supplementation. Metagenomic analysis revealed that HQ supplementation made significant structural changes in the intestinal microflora of mice fed with HFD. The Spearman's correlation analysis revealed that physiological index, serum and liver lipid profiles were positively correlated with Bacteroidales S24-7, Streptococcus, Allobaculum, and Clostridiales XIII, but negatively associated with Lactobacillus, Ruminococcaceae_NK4A214 group, Ruminiclostridium, and Alistipes. UPLC-QTOF/MS-based liver metabolomics demonstrated that HQ intervention had significant regulatory effects on the metabolic pathways of primary bile acid biosynthesis, pyrimidine metabolism, ether lipid metabolism, glutathione metabolism, glycine, serine and threonine metabolism, and amino sugar and nucleotide sugar metabolism, etc. Additionally, HQ intervention regulated the mRNA levels of hepatic genes involved in hepatic lipid metabolism and bile acid homeostasis. Collectively, these findings present new evidence supporting that HQ has the potential to ameliorate dyslipidemia and NAFLD via modulating the intestinal microbial populations and hepatic metabolite profile in hyperlipidemic mice induced by HFD.
Subject(s)
Fagopyrum , Gastrointestinal Microbiome , Monascus , Non-alcoholic Fatty Liver Disease , Animals , Asia , China , Diet, High-Fat , Metabolome , Mice , Non-alcoholic Fatty Liver Disease/prevention & controlABSTRACT
Ganoderic acid A (GA) is one of the most abundant triterpenoids in Ganoderma lucidum, and has been proved to possess a wide range of beneficial health effects. The aim of the current study is to investigate the amelioration effects and mechanism of GA on improving hyperlipidemia in mice fed a high-fat diet (HFD). The results showed that GA intervention significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, and ameliorated the biochemical parameters of serum and liver related to lipid metabolism in HFD-fed mice. Histological analysis also showed that the excessive accumulation of lipid droplets in the liver induced by HFD-feeding was greatly alleviated by GA intervention. In addition, GA intervention also increased the level of short chain fatty acids (SCFAs) in the intestine and promoted the excretion of bile acids (BAs) through feces. High-throughput sequencing of bacterial full-length 16S rDNA revealed that daily supplementation with GA made significant structural changes in the gut microbial population of mice fed with HFD, in particular modulating the relative abundance of some function related microbial phylotypes. The relationships between lipid metabolic parameters and gut microbial phylotypes were also revealed by correlation analysis based on a heatmap and network. The result showed that 46 key gut microbial phylotypes (OTUs) were markedly correlated with at least one lipid metabolic parameter. Moreover, UPLC-QTOF/MS-based liver metabolomics showed that 111 biomarkers (47 up-regulated metabolites and 64 down-regulated metabolites) were significantly changed after high-dose GA intervention (75 mg kg-1 day-1), compared with the HFD-fed hyperlipidemic mice. Metabolic pathway enrichment analysis of the differential hepatic metabolites demonstrated that GA intervention had significant regulatory effects on primary bile acid biosynthesis, fatty acid biosynthesis, amino sugar and nucleotide sugar metabolism, inositol phosphate metabolism, and so on. In addition, GA intervention regulated the mRNA levels of hepatic genes involved in fatty acid metabolism and bile acid homeostasis. These findings present new evidence supporting that GA from G. lucidum has the potential to alleviate lipid metabolic disorders and ameliorate the imbalance of gut microflora in a positive way.
Subject(s)
Gastrointestinal Microbiome/drug effects , Heptanoic Acids/pharmacology , Hyperlipidemias/therapy , Lanosterol/analogs & derivatives , Lipid Metabolism/drug effects , Reishi/chemistry , Animals , Bile Acids and Salts/metabolism , Diet, High-Fat/adverse effects , Disease Models, Animal , Fatty Acids, Volatile/metabolism , Feces/chemistry , Hyperlipidemias/etiology , Hyperlipidemias/metabolism , Lanosterol/pharmacology , Liver/metabolism , Male , Metabolomics , MiceABSTRACT
This study aimed to investigate the protective mechanism of common buckwheat (Fagopyrum esculentum Moench.) against nonalcoholic fatty liver disease (NAFLD) associated with dyslipidemia in mice that were fed a high-fat and high-cholesterol diet (HFD). Results showed that oral supplementation of common buckwheat significantly improved physiological indexes and biochemical parameters related to dyslipidemia and NAFLD in mice fed with HFD. Furthermore, the HFD-induced reductions in fecal short-chain fatty acids were reversed by common buckwheat intervention, which also increased the fecal bile acid (BA) abundance compared with HFD-induced hyperlipidemic mice. Liver metabolomics based on ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry demonstrated that common buckwheat supplementation made significant regulatory effects on the pentose phosphate pathway, starch and sucrose metabolism, primary BA biosynthesis, and so forth. The results of high-throughput sequencing revealed that common buckwheat supplementation significantly altered the structure of the intestinal microbiota in mice fed with HFD. The correlations between lipid metabolic parameters and intestinal microbial phylotypes were also revealed by the heatmap and network. Additionally, common buckwheat intervention regulated the mRNA expressions of genes responsible for liver lipid metabolism and BA homeostasis, thus promoting BA synthesis and excretion. These findings confirmed that common buckwheat has the outstanding ability of improving lipid metabolism and could be used as a potential functional food for the prevention of NAFLD and hyperlipidemia.
Subject(s)
Cholesterol/metabolism , Fagopyrum/metabolism , Hyperlipidemias/diet therapy , Non-alcoholic Fatty Liver Disease/diet therapy , Animals , Bile Acids and Salts/metabolism , Cholesterol/adverse effects , Diet, High-Fat/adverse effects , Gastrointestinal Microbiome , Humans , Hyperlipidemias/etiology , Hyperlipidemias/metabolism , Hyperlipidemias/microbiology , Liver/metabolism , Male , Mice , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/microbiologyABSTRACT
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 polysaccharidechromium (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 5.71â¯mg/mL, pHâ¯6.36, temperature 66.4⯰C and time 2.0â¯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⯱â¯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 (50â¯mg/kgâ¯day) were significantly lower than the model group (Pâ¯<â¯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.
Subject(s)
Basidiomycota/chemistry , Chromium/chemistry , Fungal Polysaccharides/chemistry , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacology , Animals , Blood Glucose , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/etiology , Diet, High-Fat , Glucose Tolerance Test , Male , Mice , Spectrum AnalysisABSTRACT
The purpose of this study was to assess the potential effects of polysaccharides from edible mushroom Grifola frondosa (GFP) on lipid metabolic disorders and gut microbiota dysbiosis, and elucidate their possible regulatory mechanisms on lipid and cholesterol metabolism in high-fat diet (HFD)-exacerbated hyperlipidemic and hypercholesterolemic rats. Results showed that oral administration of GFP markedly alleviated dyslipidaemia through decreasing the serum levels of total triglycerides, total cholesterol, and free fatty acids, and significantly suppressing hepatic lipid accumulation and steatosis. Besides, the excretion of fecal bile acids was also promoted by oral administration of GFP. Metagenomic analysis revealed that GFP supplementation (400 mg kg-1 day-1) resulted in significant structure changes on gut microbiota in HFD-fed rats, in particular modulating the relative abundance of functionally relevant microbial phylotypes compared with the HFD group. Key microbial phylotypes responding to GFP intervention were identified to strongly correlate with the lipid metabolism disorder associated parameters using the correlation network based on Spearman's correlation coefficient. Serum and hepatic lipid profiles were found positively correlated with Clostridium-XVIII, Butyricicoccus and Turicibacter, but negatively correlated with Helicobater, Intestinimonas, Barnesiella, Parasutterella, Ruminococcus and Flavonifracter. Moreover, GFP treatment (400 mg kg-1 day-1) regulated the mRNA expression levels of the genes responsible for hepatic lipid and cholesterol metabolism. Oral supplementation of GFP markedly increased the mRNA expression of cholesterol 7α-hydroxylase (CYP7A1) and bile salt export pump (BSEP), suggesting an enhancement of bile acid (BA) synthesis and excretion from the liver. These findings illustrated that GFP could ameliorate lipid metabolic disorders through modulating specific gut microbial phylotypes and regulating hepatic lipid and cholesterol metabolism related genes, and therefore could be used as a potential functional food ingredient for the prevention or treatment of hyperlipidemia.
Subject(s)
Dysbiosis/drug therapy , Gastrointestinal Microbiome/drug effects , Grifola/chemistry , Lipid Metabolism Disorders/drug therapy , Plant Extracts/administration & dosage , Polysaccharides/administration & dosage , Animals , Bacteria/classification , Bacteria/drug effects , Bacteria/genetics , Bacteria/isolation & purification , Cholesterol/blood , Cholesterol 7-alpha-Hydroxylase/genetics , Cholesterol 7-alpha-Hydroxylase/metabolism , Diet, High-Fat/adverse effects , Dysbiosis/metabolism , Dysbiosis/microbiology , Fatty Acids, Nonesterified/blood , Humans , Lipid Metabolism/drug effects , Lipid Metabolism Disorders/genetics , Lipid Metabolism Disorders/metabolism , Lipid Metabolism Disorders/microbiology , Liver/drug effects , Liver/metabolism , Male , Rats , Rats, Wistar , Triglycerides/bloodABSTRACT
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 6.97â¯mg/mL, pHâ¯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 7.0â¯mg/mL, pHâ¯7.7 and temperature 70.0⯰C), the experimental chelation rate was 28.01%⯱â¯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 (900â¯mg/kgâ¯day) were significantly lower than the diabetic group (Pâ¯<â¯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.
Subject(s)
Chromium/chemistry , Fungal Polysaccharides/chemistry , Grifola/chemistry , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacology , Animals , Blood Glucose , Diabetes Mellitus, Experimental , Diet, High-Fat , Disease Models, Animal , Lipid Metabolism/drug effects , Liver/drug effects , Liver/metabolism , Male , Mice , Spectrum Analysis , Streptozocin/adverse effectsABSTRACT
This study aimed to investigate the effects of 95% ethanol extract of G. frondosa (GF95) on lipid metabolism and gut microbiota composition in high-fat diet (HFD) fed rats. UPLC/Q-TOF MS indicated that GF95 was enriched with flavones, fatty acids and so on. Meanwhile, we found that body weight, serum lipid or liver index (total cholesterol, triglyceride, and low density lipoprotein cholesterol) levels were significantly decreased in GF95-treated HFD-fed rats. Furthermore, GF95 treatment regulated mRNA expression levels involved in lipid metabolism. GF95 consumption significantly enhanced the excretion of bile acids in the cecum. Besides, in this study, a higher abundance of Butyricimonas genus was revealed in the GF95 group, which is highly related to the highest production of short-chain fatty acids in the caecum contents among the experimental groups. Interestingly, results from network analysis showed that Butyricimonas were negatively correlated with serum and liver lipid profiles.
Subject(s)
Bacteria/drug effects , Drugs, Chinese Herbal/administration & dosage , Gastrointestinal Microbiome/drug effects , Grifola/chemistry , Hyperlipidemias/drug therapy , Lipid Metabolism/drug effects , Animals , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Cecum/metabolism , Cecum/microbiology , Cholesterol/metabolism , Diet, High-Fat/adverse effects , Drugs, Chinese Herbal/chemistry , Humans , Hyperlipidemias/etiology , Hyperlipidemias/genetics , Hyperlipidemias/metabolism , Liver/drug effects , Liver/metabolism , Male , Rats , Rats, Wistar , Triglycerides/metabolismABSTRACT
The objective of this study was to investigate the effects of ethanol extract of Ganoderma lucidum (GL95) on hyperlipidaemia and gut microbiota, and its regulation mechanism in Wistar rats fed on a high-fat diet (HFD). UPLC-QTOF MS indicated that GL95 was enriched with triterpenoids, especially ganoderic acids. The results of the animal experiment showed that oral administration of GL95 markedly alleviated the dyslipidemia through decreasing the levels of serum total triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), and inhibiting hepatic lipid accumulation and steatosis. Furthermore, GL95 supplementation altered the composition of gut microbiota, in particular modulating the relative abundance of functionally relevant enterotypes compared with the HFD group. The Spearman's correlation analysis revealed that Alistipes, Defluviitalea, Peptococcaceae and Alloprevotella were negatively correlated with serum and hepatic lipid profiles. Meanwhile, the GL95 treatment regulated the mRNA expression levels of the genes involved in lipid and cholesterol metabolism. The findings above illustrate that Ganoderma triterpenoids have the potential to ameliorate lipid metabolic disorders, in part through modulating specific gut microbiota and regulating the genes involved in lipid and cholesterol metabolism, suggesting Ganoderma triterpenoids as a potential novel functional food for the treatment or prevention of hyperlipidaemia.