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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., 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., 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., 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., 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., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: The processed radix polygoni multiflori (P-RPM) are produced from the raw radix polygoni multiflori (R-RPM) steamed with black bean juice, but the two traditional Chinese medicines are used to treat the different diseases in clinic. In order to clarify the influence of processing on pharmacological properties of radix polygoni multiflori, an investigation was carried out to compare the pharmacokinetics of typical constituents after oral administration of P-RPM and R-RPM extracts, Materials and Methods: A simple, rapid and sensitive high performance liquid chromatography-tandem mass spectroscopy (LC-MS/MS) was developed and validated for the simultaneous determination of gallic acid, polydatin, 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside (PM-SG), resveratrol, and emodin in rat plasma. Male Sprague-Dawley rats were orally administered the two extracts with approximately the same dosage., Results: It was found that gallic acid was distributed as opened one-compartment model while polydatin, PM-SG and emodin were fitted to an open two-compartment model after oral administration of raw and processed radix polygoni multiflori extract. Cmax and AUC of gallic acid were increased (P<0.01), but Cmax and AUC of PM-SG were descreased (P<0.05). AUC of polydatin and emodin were similar with that of PM-SG. However, resveratrol was not detected in plasma collected at certain intervals following oral administration of the two extracts., Conclusions: These results indicate that influence of the processing could improve the bioavailability of gallic acid and reduce the absorption of PM-SG, polydatin and emodin in rats. The LC-MS/MS method could be used to evaluate the effect of processing on pharmacokinetic of typical constituents in radix polygoni multiflori after oral administration., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: The integrated effects of herbal medicines were the outcome of all of the inherent components. Currently, few studies have focused on the multicomponent interactions in an herbal medicine to elucidate its pharmacological and/or toxicological effects. In this study, an attempt was made to investigate the interaction between stilbene glucosides and the anthraquinones contained in Radix Polygoni Multiflori (RPM) and to explore the interaction's mechanism from the perspective of UDP-glucuronosyltransferase (UGT) regulation., Materials and Methods: The extract of RPM was separated into a stilbene glucoside fraction and a emodin fraction. A rapid high-performance liquid chromatography-mass spectrometry method was developed and validated to disclose the influence of stilbene glucoside on the pharmacokinetics of emodin in rats. Drug and Statistics 2.0 was used for the estimation of the pharmacokinetic parameters. Gene expression analysis in liver and intestinal tissues was performed by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method., Results: The analytical method appeared to be suitable for the analysis of emodin with desirable linearity, accuracy, precision and stability, and the total analysis time was less than 2 min on a short column. Glucuronide of emodin, which is the major metabolite of emodin, was determined after β-glucuronidase hydrolysis. As the in vivo pharmacokinetic studies had indicated, the AUC, Cmax and T1/2 of emodin were increased after the stilbene glucoside treatment, and the glucuronidation of emodin was significantly inhibited. The mRNA levels from UGT1A8 and UGT1A2 were decreased by stilbene glucoside treatment. In contrast, the expression of UGT1A1, UGT1A6 and UGT1A9 mRNA was increased in the liver following treatment., Conclusions: The influence of stilbene glucoside on the pharmacokinetics of emodin may be attributed to the inhibition of UGT1A8 mRNA expression. Thus, it is important to extend this research to deepen our understanding of the pharmacological and/or toxicological effects of RPM., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)