Biotransformation Of Ginsenoside Rb1 Research Articles

Pharmacokinetic Profiling of Ginsenosides, Rb1, Rd, and Rg3, in Mice with Antibiotic-Induced Gut Microbiota Alterations: Implications for Variability in the Therapeutic Efficacy of Red Ginseng Extracts.

Ginsenoside Rg3 is reported to contribute to the traditionally known diverse effects of red ginseng extracts. Significant individual variations in the therapeutic efficacy of red ginseng extracts have been reported. This study aimed to investigate the effect of amoxicillin on the pharmacokinetics of ginsenosides Rb1, Rd, and Rg3 in mice following the oral administration of red ginseng extracts. We examined the α-diversity and β-diversity of gut microbiota and conducted pharmacokinetic studies to measure systemic exposure to ginsenoside Rg3. We also analyzed the microbiome abundance and microbial metabolic activity involved in the biotransformation of ginsenoside Rb1. Amoxicillin treatment reduced both the α-diversity and β-diversity of the gut microbiota and decreased systemic exposure to ginsenoside Rg3 in mice. The area under the curve (AUC) values for Rg3 in control and amoxicillin-treated groups were 247.7 ± 96.6 ng·h/mL and 139.2 ± 32.9 ng·h/mL, respectively. The microbiome abundance and microbial metabolic activity involved in the biotransformation of ginsenoside Rb1 were also altered by amoxicillin treatment. The metabolizing activity was reduced from 0.13 to 0.05 pmol/min/mg on average. Our findings indicate that amoxicillin treatment potentially reduces the gut-microbiota-mediated metabolism of ginsenoside Rg3 in mice given red ginseng extracts, altering its pharmacokinetics. Gut microbiome variations may thus influence individual ginsenoside pharmacokinetics, impacting red ginseng extract's efficacy. Our results suggest that modulating the microbiome could enhance the efficacy of red ginseng.

Biotransformation of ginsenoside Rb1 and Rd to four rare ginsenosides and evaluation of their anti-melanogenic effects.

Improving physiological activity of primary ginsenosides through biotransformation is of great significance for food applications. In this study, gynostapenoside XVII, gynostapenoside LXXV, ginsenoside F2, and ginsenoside CK were obtained by enzymolysis of an accessible extract composed of ginsenoside Rb1 and Rd. Their effects on melanin content and tyrosinase activity were compared in vitro, and molecular docking simulation was employed to elucidate the interaction between tyrosinase and individual saponin. The results indicated that four rare ginsenosides decreased tyrosinase activity, melanin content and microphthalmia-associated transcription factor (MITF) expression level, more greatly than their primary ginsenosides, and they were more readily to bind with ASP10 and GLY68 at active site of tyrosinase to inhibit tyrosinase activity as well. These findings suggested that the rare ginsenosides obtained by enzymolysis had excellent anti-melanogenic effect, which could expand the application of ginsenosides in the field of functional foods and health supplements.

Biotransformation of ginsenoside Rb1 with wild Cordyceps sinensis and Ascomycota sp. and its antihyperlipidemic effects on the diet-induced cholesterol of zebrafish.

Biotransformation major ginsenoside into minor ginsenoside via microbial fermentation has been proposed as a viable option to produce minor ginsenoside, becauseof its biological activity superior to major ginsenoside. Cordyceps sinensis contains a complex enzymatic system and many ingredients with medicinal value that could be useful tools for biotransformation applications in the ginseng industry. Wild C. sinensis and Ascomycota sp. were collected from Changbai Mountain and identified. Analysis by UPLC-MS and HPLC indicates that the underlying pathway of major ginsenoside Rb1 during fermentation with strains was Rb1→Rd→F2→CK and Rb1→Rd→Rg3. C. sinensis and Ascomycota sp. can be applied to minor ginsenoside preparation in the food and medical industries. The antihyperlipidemic effects of Rb1 were further screened from fermentation in larvae zebrafish based on the fluorescence intensity. In the adult zebrafish model, treatment with high-dose ginsenoside Rb1 group exhibited a significant decrease in the plasma total cholesterol (TC) and triglyceride (TG) levels by 36.49% (p<.05) and 29.97% (p<.05), respectively, compared with high cholesterol group (HC). Furthermore, ginsenoside Rb1 treatment decreased the mRNA levels of LDLR and SREBP2 in the adult zebrafish liver. Ginsenoside Rb1 diet supplement significantly increased the mRNA expression of HMGCR and CYP7A1. These results suggest that ginsenoside Rb1 attenuates hypercholesterolemia via the downregulation of cholesterol synthesis and assembly or secretion of lipoproteins as well as the upregulation of cholesterol transport and efflux, providing a novel idea of ginsenoside keeping cholesterol levels down for the clinical application. PRACTICAL APPLICATIONS: Wild Cordyceps sinensis has the potential to be applied to the preparation for minor ginsenoside. Furthermore, the final fermentation product has more functional characteristics, including cordyceps acid, cordycepin, and adenosine. Wild Cordyceps sinensis and Ascomycota sp. could potentially be employed in the food and medical industries.

New metabolites from the biotransformation of ginsenoside Rb1 by Paecilomyces bainier sp.229 and activities in inducing osteogenic differentiation by Wnt/β-catenin signaling activation

BackgroundGinseng is a well-known traditional Chinese medicine that has been widely used in a range of therapeutic and healthcare applications in East Asian countries. Microbial transformation is regarded as an effective and useful technology in modification of nature products for finding new chemical derivatives with potent bioactivities. In this study, three minor derivatives of ginsenoside compound K were isolated and the inducing effects in the Wingless-type MMTV integration site (Wnt) signaling pathway were also investigated. MethodsNew compounds were purified from scale-up fermentation of ginsenoside Rb1 by Paecilomyces bainier sp. 229 through repeated silica gel column chromatography and high pressure liquid chromatography. Their structures were determined based on spectral data and X-ray diffraction. The inductive activities of these compounds on the Wnt signaling pathway were conducted on MC3T3-E1 cells by quantitative real-time polymerase chain reaction analysis. ResultsThe structures of a known 3-keto derivative and two new dehydrogenated metabolites were elucidated. The crystal structure of the 3-keto derivative was reported for the first time and its conformation was compared with that of ginsenoside compound K. The inductive effects of these compounds on osteogenic differentiation by activating the Wnt/β-catenin signaling pathway were explained for the first time. ConclusionThis study may provide a new insight into the metabolic pathway of ginsenoside by microbial transformation. In addition, the results might provide a reasonable explanation for the activity of ginseng in treating osteoporosis and supply good monomer ginsenoside resources for nutraceutical or pharmaceutical development.

Biotransformation of ginsenoside Rb1 into F-2 and compound K by bacterium Sphingomonas sp. BG 25

Biotransformation of ginsenoside Rb1 into F-2 and compound K by bacterium Sphingomonas sp. BG 25

Biotransformation of ginsenoside Rb1 via the gypenoside pathway by human gut bacteria

BackgroundBacterial conversion of ginsenosides is crucial for the health-promoting effects of ginsenosides. Previous studies on the biotransformation of ginsenoside Rb1 (Rb1) by gut bacteria have focused on the ginsenoside Rd (Rd) pathway (Rb1 → Rd → ginsenoside F2 (F2) → compound K (Cpd K)). This study aims to examine the gypenoside pathway in human gut bacteria in vitro.MethodsThe metabolic pathways of ginsenoside Rb1 and its metabolites ginsenoside Rd and gypenoside XVII in human gut bacteria were investigated by incubating the compounds anaerobically with pooled or individual gut bacteria samples from healthy volunteers. Ginsenoside Rb1, the metabolites generated by human gut bacteria, and degraded products in simulated gastric fluid (SGF) were qualitatively analyzed using an LC/MSD Trap system in the negative ion mode and quantitatively determined by HPLC-UV analysis.ResultsWhen incubated anaerobically with pooled gut bacteria, Rb1 generated five metabolites, namely Rd, F2, Cpd K, and the rare gypenosides XVII (G-XVII) and LXXV (G-LXXV). The gypenoside pathway (Rb1 → G-XVII → G-LXXV → Cpd K) was rapid, intermediate, and minor, and finally converted Rb1 to Cpd K via G-XVII → F2 (major)/G-LXXV (minor). Both the Rd and gypenoside pathways exhibited great inter-individual variations in age-and sex-independent manners (P > 0.05). Rb1 was highly acid-labile and degraded rapidly to form F2, ginsenoside Rg3, ginsenoside Rh2, and Cpd K, but did not generate the gypenosides in SGF. The formation of the gypenosides might be explained by the involvement of a gut bacteria-mediated enzymatic process.ConclusionsRb1 was metabolized to G-XVII, F2 (major) or G-LXXL (minor), and finally Cpd K by human gut bacteria in vitro.

Biotransformation of Ginsenoside Rb1 into Rd by the Bacterium Lysobacter panaciterrae

Triterpenoid saponins and ginsenosides, the majority of which contain the aglycons protopanaxadiol or protopanaxatriol, are important biologically active compounds of Panax ginseng C. A. Meyer. The principal ginsenoside, the content of which in ginseng root is >20% of the total saponins, is Rb1 (1), which includes -sophorose and -gentiobiose residues (6-O-Dglucopyranosyl-D-glucose) in the C-3 and C-20 positions, respectively, of 20(S)-protopanaxadiol. The minor ginsenoside Rd (2) is a close structural analog of Rb1 and has a glucose instead of -gentiobiose in the C-20 position [1]. Rd has a broader spectrum of biological activity than Rb1, for example, it increases the differentiation of nerve stem cells, protects neurons from neurotoxic substances, and inhibits proliferation of HepG2 liver cancer cells [2]. However, the content of Rd in ginseng root is 4–5 times less than that of Rb1. Therefore, biotransformation of ginsenoside Rb1 into Rd, in particular by using microorganisms, is of practical importance [3].