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      Enhanced absorption and inhibited metabolism of emodin by 2, 3, 5, 4′-tetrahydroxystilbene-2- O- β-D-glucopyranoside: Possible mechanisms for Polygoni Multiflori Radix-induced liver injury

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          Polygoni Multiflori Radix (PMR) has been commonly used as a tonic in China for centuries. However, PMR-associated hepatotoxicity is becoming a safety issue. In our previous in vivo study, an interaction between stilbenes and anthraquinones has been discovered and a hypothesis is proposed that the interaction between stilbene glucoside-enriching fraction and emodin may contribute to the side effects of PMR. To further support our previous in vivo results in rats, the present in vitro study was designed to evaluate the effects of 2, 3, 5, 4′-tetrahydroxystilbene-2- O- β-D-glucopyranoside (TSG) on the cellular absorption and human liver microsome metabolism of emodin. The obtained results indicated that the absorption of emodin in Caco-2 cells was enhanced and the metabolism of emodin in human liver microsomes was inhibited after TSG treatment. The effects of the transport inhibitors on the cellular emodin accumulation were also examined. Western blot assay suggested that the depressed metabolism of emodin could be attributed to the down-regulation of UDP-glucuronosyltransferases (UGTs) 1A8, 1A10, and 2B7. These findings definitively demonstrated the existence of interaction between TSG and emodin, which provide a basis for a better understanding of the underlying mechanism for PMR-induced liver injury.

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          Author and article information

          Chinese Journal of Natural Medicines
          20 June 2017
          : 15
          : 6
          : 451-457
          1State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
          Author notes
          *Corresponding author: LI Hui-Jun, Tel: 86-25-83271382, Fax: 86-25-83271379, E-mail: cpuli@ 123456163.com .

          ΔThese authors contributed to the work equally.

          These authors have no conflict of interest to declare.

          Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funded by: National Natural Science Foundation of China
          Award ID: 81573562
          Award ID: 81322051
          Award ID: 81073007
          Funded by: Natural Science Foundation of Jiangsu Province
          Award ID: BK20151442
          This work was supported by the National Natural Science Foundation of China (Nos. 81573562, 81322051, and 81073007) and the Natural Science Foundation of Jiangsu Province (No. BK20151442).


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