Changes in intestinal microbiota affect metabolism of ginsenoside Re

Abstract

Ginsenoside Re, an active ingredient in Panax ginseng, is widely used as a therapeutic and nutriment. The intestinal microbiota plays crucial roles in modulating the pharmacokinetics and pharmacological actions of ginsenoside Re. The aim of this study was to explore the relationship between bacterial community variety and the metabolic profiles of ginsenoside Re. We developed two models with intestinal dysbacteriosis: a pseudo-germ-free model induced by a nonabsorbable antimicrobial mixture (ATM), and Qi-deficiency model established via over-fatigue and acute cold stress (OACS). First, the bacterial community structures in control, ATM and OACS rats were compared via 16S ribosomal RNA amplicon sequencing. Then, the gut microbial metabolism of ginsenoside Re was assessed qualitatively and quantitatively in the three groups by UPLC-Q-TOF/MS and HPLC-TQ-MS, respectively. Ten metabolites of ginsenoside Re were detected and tentatively identified, three of which were novel. Moreover, owing to significant differences in bacterial communities, deglycosylated products, as the main metabolites of ginsenoside Re, were produced at lower levels in ATM and OACS models. Importantly, the levels of these deglycosylated metabolites correlated with alterations in Prevotella, Lactobacillus and Bacteroides populations, as well as glycosidase activities. Collectively, biotransformation of ginsenoside Re is potentially influenced by regulation of the composition of intestinal microbiota and glycosidase activities.

The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

“…Another non-pharmacological approach is the oral administration of ginseng that has been shown to have anti-fatigue properties in ME/CFS, cancer-related fatigue and MS-related fatigue in several blinded randomizedcontrolled studies (34)(35)(36)(37). Just recently, it was suggested that the related pharmacokinetics are mediated via the gut microbiome (278,279). While these indications are all indirect and thus cannot be considered conclusive, even though randomized controlled trials are considered relatively strong evidence, they support the general principle of effective fatigue reduction accompanying changes to the gut microbiome in similar conditions, which makes assessment of whether the same applies in the ME/CFS setting relevant to test further.…”

Effect of the Chinese Medicine YangZheng XiaoJi on Reducing Fatigue in Mice with Orthotopic Transplantation of Colon Cancer

“…At genus level, the abundance of Parabacteroides , unidentified Saprospiraceae , and Elizabethkingia in Bacteroidetes were increased and Arcobacter, Marinobacter , Alkanindiges, Sulfuricurvum, Haliangium, and Thiobacillus belonging to Proteobacteria were decreased in YZXJ group. A large amount of data confirmed that Bacteroides can promote the metabolism of ginsenoside that indirectly improves the state of physical fatigue [64, 65]. Proteobacteria mainly include Helicobacter and Shigella , both of them can promote the occurrence of CRC by inducing inflammatory reaction and also play an important role in causing CRF [66–68].…”

Advances and challenges in ginseng research from 2011 to 2020: the phytochemistry, quality control, metabolism, and biosynthesis

“…As a class of glycoside compounds, the ginsenosides in ginseng drugs after oral administration can be largely transformed by the gut microorganism, and the obtained metabolites together with the prototype compounds are absorbed. Identification of the in vitro (co-cultured with the intestinal flora from healthy human or animals, 327–330 or rat liver microsomes 331 ) and in vivo metabolites (from the healthy human or animal plasma, urine, bile, feces or zebrafish 332–341 ) of ginsenosides was performed by LC-MS. Information on the identified metabolites for the ginsenoside analytes has been given in Table S7 † 327–340,342–344 . In general, the hydrophilic ginsenosides are metabolized to hydrophobic compounds by gastric juices and gut microbiota: (1) the PPD-type ginsenosides are mainly transformed into compound K (CK) and Rh2; (2) the PPT-type to Rh1 and the PPT sapogenin; (3) the OT-type to ocotillol.…”

“…332 The feces of rats after the administration of Re were analyzed and 10 metabolites were detected and identified, three of which were new compounds. 340 The metabolites of noto-R1, Rg1, and Rb1 in zebrafish were studied by HPLC-ESI-MS, and deglycosylated metabolites and hydroxylation metabolites of these three saponins were identified. 335…”