Effect Of Ginseng Polysaccharides On Metabolism Of Ginsenoside And The Synergistic Effect Of Ginsenoside And Red Ginseng Polysaccharide For Diabetic Treatment

Objective:Ginsenosides exhibits poor oral bioavailability.Recent research indicated that ginsenosides is inevitably exposed to intestinal microbiota after oral administration and is transformed to metabolites that are more readily absorbed into the bloodstream and act with improved pharmaceutical activity.Polysaccharides play an important role in the regulation of intestinal bacterial flora.In this study,the effect of GP on the transformation of ginsenoside Re by intestinal flora was observed,and the pharmacokinetic of the metabolite Rg1 of ginsenoside Re were further discussed.Recently,ginsenoside Rb1 displays significantly hypoglycemic activity.Red Ginseng polysaccharides?GP?have been reported to modulate gut microbiota.However,the synergistic effect of Rb1 and GP for diabetic treatment remains largely unknown.In this study,the rat model of type 2 diabetes was established by intraperitioneal injection of low dose streptozotocin and high fat diet.The synergistic effect of Rb1 and GP for diabetic treatment was observed and the possible mechanism and material base of its action was discussed.Methods:1.Effects of red ginseng polysaccharides on the metabolism of ginsenoside in vivoRapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry?RRLC/Q-TOF-MS?was performed to investigate the biotransformation process of ginsenoside Re by intestinal microflora in media containing or no red ginseng polysaccharides and the pharmacokinetics of the ginsenoside Re metabolite,ginsenoside Rg1,in rats with or without pretreatment with red ginseng polysaccharides.2.Study on material basis and mechanism of the synergistic effect of ginsenoside and ginseng polysaccharide for diabetic treatmentMale rats were divided into ten groups:blank group?B-Group?,model group?D-Group?,Rb1 group?Rb1-Group?,CK group?CK-Group?,GP groups and GP+Rb1groups in dosage of high,middle and low?H-Group,M-Group,L-Group,H-Rb1-Group,M-Rb1-Group,and L-Rb1-Group?.CK-Group,GP groups and Rb1 group were fed CK,GP and Rb1 for 30 days,respectively.GP+Rb1 groups were fed GP on the initial 15 days and GP and Rb1 on the final 15 days.The fasting glucose of all groups was measured every five days.The transformation of Rb1 in vitro by rat intestinal microflora,which was collected from the B-Group,D-Group and GP groups on the 15th day,was investigated using HPLC and RRLC-Q-TOF/MS.Analysis of 16S rRNA gene of the fecal bacteria population and the fecal?-glucosidase activity were conducted in B-Group,D-Group and H-Group.Results:1.Effects of red ginseng polysaccharides on the metabolism of ginsenoside in vivoFor transformation of Re by rat intestinal microflora,five transformed products including ginsenoside Rg1,Rh1,Rg2,F1 and PPT,as well as three transformation pathways were identified.When the intestinal microbiota of rat feces was cultured in vitro,their ginsenoside Re biotransformation activities were significantly induced by red ginseng polysaccharides.When ginsenoside Re was orally administered to rats,the peak time(t_max),the maximum plasma concentration(c_max)and area under the plasma drug concentration–time curve?AUC?for the main metabolite,ginsenoside Rg1,were?11.6±6.1?h,?80.1±44.0?ng/mL and?549.3±209.4??g·h/mL,respectively.When ginsenoside Re was orally administered to rats fed red ginseng polysaccharides,t_max,c_max and AUC for ginsenoside Rg1 were?8.2±5.4?h,?98.2±50.6?ng/mL and?691.9±231.2?ng?h/mL,respectively.2.Study on material basis and mechanism of the synergistic effect of ginsenoside and ginseng polysaccharide for diabetic treatmentCompared with D-Group,the fasting glucose in CK-Group and H-Rb1-Group rats decreased highest.For transformation of Rb1 by diabetic rat intestinal microflora,five transformed products including ginsenoside Rd,F2,CK,gypenoside XVII?G-XVII?and LXXV?G-LXXV?,and three transformation pathways were identified.When high dose of GP was fed to diabetic rats for 15 days,the formation of intermediates including G-XVIIand G-LXXV were inhibited and only one pathway?Rb1?Rd?F2?CK?was identified.Moreover,biotransformation rate of CK increased from 14.0%to 86.7%after 8 h of cultivation.Red ginseng polysaccharides reinstated the perturbed holistic gut microbiota and promoted the fecal?-d-glucosidase activity.Conclusion:1.The results show that red ginseng polysaccharides may promote the metabolic conversion of ginsenoside Re to Rg1 and the subsequent absorption of Rg1 in the gastrointestinal tract and may potentiate the pharmacological effects of ginseng.2.GinsenosideRb1 and GP showed synergistic effect for diabetic treatment,and might be used as antidiabetic drug candidate.