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, 2019, 9348075
eCollection

Comparative Pharmacokinetic Study of Taxifolin After Oral Administration of Fructus Polygoni Orientalis Extract in Normal and Fibrotic Rats by UPLC-MS/MS

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Comparative Pharmacokinetic Study of Taxifolin After Oral Administration of Fructus Polygoni Orientalis Extract in Normal and Fibrotic Rats by UPLC-MS/MS

Feili Wei et al. Evid Based Complement Alternat Med.

Abstract

Fructus polygoni orientalis (FPO) is widely used in clinical practice in China, especially in treatment of liver diseases including viral hepatitis, liver fibrosis, and liver cirrhosis. However, its pharmacokinetic (PK) alterations in liver fibrotic rats have rarely been reported. To study whether taxifolin, one of the main flavonoids in FPO can be absorbed into blood after oral administration of FPO extract and to compare the differences in pharmacokinetic parameters of taxifolin to normal and liver fibrotic rats induced by porcine serum (PS), a UPLC-MS/MS method was developed and validated for determination of taxifolin in rat plasma using puerarin as the internal standard (IS). All validation parameters met the acceptance criteria according to regulatory guidelines. The results indicated that after treatment of rats with PS alone for 12 weeks, the liver fibrotic model group was built successfully. The taxifolin can be absorbed into the blood after oral administration of the FPO extract. The C max of taxifolin was 1940 ± 502.2 ng/mL and 2648 ± 208.5 ng/mL (p < 0.05), the AUC0∼t of taxifolin was 4949.7 ± 764.89 h·ng/mL and 6679.9 ± 734.26 h·ng/mL (p < 0.05), the AUC0∼∞ of taxifolin was 5049.4 ± 760.7 and 7095.2 ± 962.3 h·ng/mL (p < 0.05), and the mean residence time (MRT) of taxifolin was 2.46 ± 0.412 h and 3.17 ± 0.039 h (p < 0.05) in the normal and fibrotic model groups, respectively. These results confirmed that the pharmacokinetic parameters of taxifolin are altered in liver fibrosis, manifested as C max, AUC0∼t , AUC0∼∞, and the mean residence time (MRT). It suggested that it is essential to consider the characteristics of pharmacokinetics after oral administration of FPO in liver disease patients.

Conflict of interest statement

The authors declare that there are no conflicts of interests regarding the publication of this paper.

Figures

Figure 1
Figure 1
Full-scan product ion spectra of [M + H]+ ions and fragmentation schemes for (a) taxifolin and (b) puerarin (internal standard).
Figure 2
Figure 2
Typical chromatograms of (a) blank rat plasma; (b) blank rat plasma spiked with taxifolin (10 ng/mL, LLOQ) and IS; and (c) an normal rat plasma sample collected at 1 h after oral administration of 1.23 g/kg extract of FPO; (d) a model rat plasma sample collected at 10 min after oral administration of 1.23 g/kg extract of FPO.
Figure 3
Figure 3
The fold change of mRNA expression level of 3 fibrosis-related genes including aSMA, Collagen1A1, and Collagen3A1 in liver tissues detected by qRT-PCR after PS treatment for 12 weeks. Data are expressed as mean ± SD(n = 3). #p < 0.05.
Figure 4
Figure 4
Photomicrographs of liver sections stained by (H&E) and Masson's trichrome staining (magnification 200x). Representative histological images of H&E stained rat liver tissue in the (a) normal group (normal), (b) PS-induced fibrotic group (model), respectively. Arrows indicate inflammatory cells infiltration. Representative histological images of Masson's trichrome stained rat liver tissue in the liver tissue in the (c) normal group (normal), (d) PS-induced fibrotic group (model), respectively. Arrows indicate the collagen fibers between the portal region and pseudolobules.
Figure 5
Figure 5
Mean plasma concentration-time profiles of taxifolin determined by the UPLC-MS/MS method after oral administration of FPO extract to rats. Each point represents the mean ± SD (n = 3).

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