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Hepatotoxic assessment of Polygoni Multiflori Radix extract and toxicokinetic study of stilbene glucoside and anthraquinones in rats.
- Source :
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Journal of ethnopharmacology [J Ethnopharmacol] 2015 Mar 13; Vol. 162, pp. 61-8. Date of Electronic Publication: 2014 Dec 31. - Publication Year :
- 2015
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Abstract
- Ethnopharmacological Relevance: Polygoni Multiflori Radix (PMR) has been traditionally used as a tonic and an anti-aging remedy for centuries; however, hepatic lesions linked to PMR have been frequently reported.<br />Aim of the Study: This work attempted to investigate the hepatotoxic potential of PMR extract and the toxicokinetics of stilbene glucoside and anthraquinones in PMR extract following repeated administration.<br />Materials and Methods: Histopathological and biochemical tests were performed to assess the hepatotoxicity of PMR extract. A rapid and sensitive liquid chromatography-mass spectrometry (LC-MS) assay was developed for toxicokinetic analysis of the main constituents of PMR extract, including 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), emodin-8-O-β-D-glucoside and emodin.<br />Results: The histopathological and biochemical tests indicated that repeated administration of high-dose PMR extract (20 g/kg) for 3 weeks could cause hepatic lesions, while the low-dose treatment (1 g/kg) was safe. Necrosis and steatosis of hepatic cells, inflammatory cell infiltration and mild fibrosis were the main toxicity symptoms caused by high-dose PMR extract in rat liver. The aspartate aminotransferase (AST) levels increased by approximately 17%, from 110.80±0.84 to 129.75±10.83 IU/L, in the high-dose group compared with the control group. The proposed LC-MS method was proven to be suitable for the simultaneous quantification of these three constituents by affording desirable linearity (r(2)>0.998) and satisfactory precision (error less than 10%). The toxicokinetic study showed that emodin could not be detected in the low-dose group, but the AUC and Cmax of emodin displayed a gradual increase with repeated treatments in the high-dose group. The toxicokinetics of TSG in the low- and high-dose groups exhibited similar trends after repeated administration.<br />Conclusions: Consideration needs to be given to the rational application of PMR in the clinic to balance its benefits and risks. The increased emodin exposure in vivo provided a putative explanation for the observed hepatic lesions induced by PMR extract, although further studies to confirm the potentially causal link between emodin exposure and hepatic lesions are still necessary.<br /> (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Chemical and Drug Induced Liver Injury metabolism
Chemical and Drug Induced Liver Injury pathology
Emodin analogs & derivatives
Emodin blood
Glucosides blood
Liver pathology
Male
Plant Extracts blood
Plant Roots
Rats, Sprague-Dawley
Stilbenes blood
Toxicokinetics
Liver drug effects
Plant Extracts pharmacokinetics
Plant Extracts toxicity
Polygonum
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7573
- Volume :
- 162
- Database :
- MEDLINE
- Journal :
- Journal of ethnopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 25557036
- Full Text :
- https://doi.org/10.1016/j.jep.2014.12.045