Prebiotics enhance the biotransformation and bioavailability of ginsenosides in rats by modulating gut microbiota

Abstract

Background Gut microbiota mainly function in the biotransformation of primary ginsenosides into bioactive metabolites. Herein, we investigated the effects of three prebiotic fibers by targeting gut microbiota on the metabolism of ginsenoside Rb1 in vivo . Methods Sprague Dawley rats were administered with ginsenoside Rb1 after a two-week prebiotic intervention of fructooligosaccharide, galactooligosaccharide, and fibersol-2, respectively. Pharmacokinetic analysis of ginsenoside Rb1 and its metabolites was performed, whilst the microbial composition and metabolic function of gut microbiota were examined by 16S rRNA gene amplicon and metagenomic shotgun sequencing. Results The results showed that peak plasma concentration and area under concentration time curve of ginsenoside Rb1 and its intermediate metabolites, ginsenoside Rd, F2, and compound K (CK), in the prebiotic intervention groups were increased at various degrees compared with those in the control group. Gut microbiota dramatically responded to the prebiotic treatment at both taxonomical and functional levels. The abundance of Prevotella , which possesses potential function to hydrolyze ginsenoside Rb1 into CK, was significantly elevated in the three prebiotic groups (P < 0.05). The gut metagenomic analysis also revealed the functional gene enrichment for terpenoid/polyketide metabolism, glycolysis, gluconeogenesis, propanoate metabolism, etc. Conclusion These findings imply that prebiotics may selectively promote the proliferation of certain bacterial stains with glycoside hydrolysis capacity, thereby, subsequently improving the biotransformation and bioavailability of primary ginsenosides in vivo .

Recent Analytical Approaches for the Study of Bioavailability and Metabolism of Bioactive Phenolic Compounds

“…Considering the limitations of NMR and GC-MS mentioned above, we can see that LC-MS has been the most widely used analytical platform in bioavailability and metabolism studies of phenolic compounds. Regarding the LC technique, HPLC and UHPLC instruments have been used in these studies [76]. UHPLC is characterized by resisting higher pressures, thus allowing the use of columns with smaller particle size that achieve higher chromatographic resolution and shorter analysis times, among other advantages [77].…”

“…Typical pharmacokinetic parameters, such as maximum plasma concentration (C max ), area under the plasma concentration-time curve (AUC), time to reach Cmax (t max ) or halflife of elimination (t 1/2 ), are generally calculated in bioavailability and pharmacokinetics studies [76,87]. Some specific software programs or tools have been used to calculate these parameters, such as the PKSolver tool from Microsoft Excel [88].…”

“…There is also a variety of statistical tests used in these studies, with the most frequent being univariate analyses, such as analysis of variance (ANOVA) and non-parametric Wilcoxon test [43,76]. Recently, multivariate statistical methods, such as principal component analysis (PCA), partial-least-squares discriminant analysis (PLS-DA), hierarchical clustering analysis or heatmaps, have been also being applied to identify biomarkers from ingestion, especially in untargeted screening studies [96].…”

Prebiotic Impacts of Soybean Residue (Okara) on Eubiosis/Dysbiosis Condition of the Gut and the Possible Effects on Liver and Kidney Functions

“…A microarray study confirms that high-amylose resistant starch could improve hormones as well as structure and function of the gut via increasing the levels of Hif-1α expression together with genes related to cell growth, differentiation, apoptosis, and proliferation in the cecal tissue of rats supplemented with 30% resistant starch in contrast with rats fed an equal amount of energy from a low-fiber diet [ 172 ]. A recent study by Zhang et al [ 173 ] evaluated the effects of prebiotics on bioavailability and biotransformation of ginsenosides in rats after a two-week prebiotic (i.e., galactooligosaccharide, fructooligosaccharide, and fibersol-2) intervention. The results displayed that area under concentration-time curve and peak plasma concentration of ginsenoside and its intermediate metabolites in the prebiotic intervention groups were improved at various degrees than those in the control group.…”

Ginsenosides Improve Nonalcoholic Fatty Liver Disease via Integrated Regulation of Gut Microbiota, Inflammation and Energy Homeostasis

“…Mey., is used as a traditional Chinese medicine and an adaptogen for thousands of years to ameliorate weakness and fatigue, prolong life, improve emotional well-being, and tonify body ( Jia and Zhao, 2009 ; Patel and Rauf, 2017 ). Ginsenosides are the major active components, and various biological functions were recognized, such as effects against obesity, hyperglycemia and NAFLD ( Hwang et al, 2018 ; Li and Ji, 2018 ; Xu et al, 2020 ; Zhang et al, 2020 ). However, the above-described research mainly focused on the activities and mechanisms of a single component, and the synergetic and comprehensive effects of multiple components remain unclear.…”