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. 2024 Aug 23;19(8):e0307286.
doi: 10.1371/journal.pone.0307286. eCollection 2024.

In vivo pharmacokinetics of ginsenoside compound K mediated by gut microbiota

Ming-Si Deng  1   2 , Su-Tian-Zi Huang  3 , Ya-Ni Xu  2 , Li Shao  4 , Zheng-Guang Wang  5 , Liang-Jian Chen  1 , Wei-Hua Huang  3   6
Affiliations

In vivo pharmacokinetics of ginsenoside compound K mediated by gut microbiota

Ming-Si Deng et al. PLoS One. .

Abstract

Ginsenoside Compound K (GCK) is the main metabolite of natural protopanaxadiol ginsenosides with diverse pharmacological effects. Gut microbiota contributes to the biotransformation of GCK, while the effect of gut microbiota on the pharmacokinetics of GCK in vivo remains unclear. To illustrate the role of gut microbiota in GCK metabolism in vivo, a systematic investigation of the pharmacokinetics of GCK in specific pathogen free (SPF) and pseudo-germ-free (pseudo-GF) rats were conducted. Pseudo-GF rats were treated with non-absorbable antibiotics. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was validated for the quantification of GCK in rat plasma. Compared with SPF rats, the plasma concentration of GCK significantly increased after the gut microbiota depleted. The results showed that GCK absorption slowed down, Tmax delayed by 3.5 h, AUC0-11 increased by 1.3 times, CLz/F decreased by 0.6 times in pseudo-GF rats, and Cmax was 1.6 times higher than that of normal rats. The data indicated that gut microbiota played an important role in the pharmacokinetics of GCK in vivo.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Validation of pseudo-GF model in rats.
(a) Body weights of rats in both normal and pseudo-GF rats after oral antibiotics (n = 5); (b) Concentration of gut microbial DNA in feces (data were expressed as mean ± SD, n = 7); SPF, normal control group; pseudo-GF, pseudo-germ-free group, ****p < 0.0001.
Fig 2
Fig 2
Mass spectra and fragmentation pathways of GCK (a), PPD (b) in negative ion mode. (c) The MRM transitions of GCK and PPD.
Fig 3
Fig 3. Typical MRM chromatograms of blank rat plasma and/or spiked with analytes and IS.
(a), (c), and (e) were the chromatograms of blank plasma; (b), (d), and (f) were the chromatograms of GCK, PPD and digoxin, respectively.
Fig 4
Fig 4. Typical MRM Chromatograms of GCK at checkpoints in the plasma of SPF group and pseudo-GF group.
(a1), (a2), (a3), (a4), and (a5) were typical MRM chromatograms of GCK at 1 h, 2.5 h, 4 h, 6 h, and 11 h in SPF group, respectively. (b1), (b2), (b3), (b4), and (b5) were typical MRM chromatograms of GCK at 1 h, 2.5 h, 4 h, 6 h, 11 h in pseudo-GF group, respectively.
Fig 5
Fig 5. The mean plasma concentration–time profiles of GCK in rat plasma after intragastric administration of GCK (22.5 mg/kg); each point and bar represent the mean ± SD (n = 7), *p < 0.05, **p < 0.01 and ***p < 0.001.
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