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[Metabolism of paeoniflorin by rat intestinal flora in vitro]
Zhong-Cheng Ke1,2,3, Nan Yang2,3, Xue-Feng Hou2,4
1College of Chemistry, Huangshan University, Huangshan 245041, China.
Abstract:
In order to clarify the effect of intestinal flora on the absorption and metabolism of paeoniflorin in vivo, the metabolism of paeoniflorin by rat intestinal flora was studied under the in vitro anaerobic condition. Paeoniflorin was incubated with rat anaerobic intestinal flora for 48 h, and UPLC was used to detect the changes of paeoniflorin at different incubation time points under the following chromatographic conditions:WelchromTM C₁₈ chromatographic column (4.6 mm×100 mm, 5 μm), with 0.1% formic acid(A)-acetonitrile(B) as the mobile phase for gradient elution. The flow rate was 0.4 mL•min⁻¹, and column temperature was 30 ℃. UPLC-Q-TOF-MS with positive ion mode(ESI ion source) was applied to investigate the structural characterization of metabolic products. The structures of the metabolites were identified by accurate molecular weight, TOF-MS/MS fragmentation information, combined with retention time and literature data review, and the intestinal metabolic rules were then analyzed. After incubation for 24 h, the paeoniflorin was metabolized completely, and the resulting metabolites(albiflorin, albiflorinaglycone, deacylate albiflorin, deacylate albiflorin aglycone and paeonilactone-B) were detected in rat intestinal flora. The metabolic pathway analysis showed that the isolated rat intestinal flora first transformed peoniflorin into albiflorin, and then further metabolized by glucose removal, phenyl group removal, or four-membered ring pyrolysis and rearrangement. Paeoniflorin was gradually transformed into more hydrophobic metabolites with smaller molecular mass, which were better absorbed by the intestinal tract.
Insights
Rat intestinal flora completely metabolizes paeoniflorin within 24 hours, producing more hydrophobic compounds like albiflorin. These metabolites are better absorbed in the intestines, influencing paeoniflorin
Area of Science:
- Pharmacology
- Microbiology
- Natural Products Chemistry
Background:
- Paeoniflorin, a key compound in traditional Chinese medicine, undergoes significant transformations in the body.
- Understanding the role of intestinal flora in paeoniflorin metabolism is crucial for its therapeutic efficacy and bioavailability.
Purpose of the Study:
- To investigate the in vitro metabolism of paeoniflorin by rat intestinal flora.
- To identify the metabolites of paeoniflorin and elucidate its metabolic pathway in the gut.
Main Methods:
- Incubation of paeoniflorin with rat anaerobic intestinal flora for 48 hours.
- Analysis using Ultra-Performance Liquid Chromatography (UPLC) for separation and detection.
- Structural characterization of metabolites via UPLC-Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF-MS) with positive ion mode.
Main Results:
- Paeoniflorin was completely metabolized within 24 hours.
- Identified metabolites include albiflorin, albiflorinaglycone, deacylate albiflorin, deacylate albiflorin aglycone, and paeonilactone-B.
- Metabolic pathway involves glucose removal, phenyl group removal, and ring rearrangement, leading to more hydrophobic compounds.
Conclusions:
- Rat intestinal flora significantly transforms paeoniflorin into various metabolites.
- The metabolic process enhances the hydrophobicity and molecular mass of paeoniflorin derivatives.
- These findings suggest improved intestinal absorption of paeoniflorin metabolites, impacting its in vivo efficacy.
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