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Screening for main components associated with the idiosyncratic hepatotoxicity of a tonic herb, Polygonum multiflorum

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Abstract

The main constituents of a typical medicinal herb, Polygonum multiflorum (Heshouwu in Chinese), that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide (LPS) and therapeutic dose of Heshouwu can induce liver injury in rats, whereas the solo treatment cannot induce observable injury. In the present work, using the constituent “knock-out” and “knock-in” strategy, we found that the ethyl acetate (EA) extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Results indicated a significant elevation of plasma alanine aminotransferase, aspartate aminotransferase, and liver histologic changes, whereas other separated fractions failed to induce liver injury. The mixture of EA extract with other separated fractions induced comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Chemical analysis further revealed that 2,3,5,4′-tetrahydroxy trans-stilbene-2-O-β-glucoside (trans-SG) and its cis-isomer were the two major compounds in EA extract. Furthermore, the isolated cis-, and not its trans-isomer, displayed comparable idiosyncratic hepatotoxicity to EA extract in LPS-treated rats. Higher contents of cis-SG were detected in Heshouwu liquor or preparations from actual liver intoxication patients associated with Heshouwu compared with general collected samples. In addition, plasma metabolomics analysis showed that cis-SG-disturbing enriched pathways remarkably differed from trans-SG ones in LPS-treated rats. All these results suggested that cis-SG was closely associated with the idiosyncratic hepatotoxicity of Heshouwu. Considering that the cis-trans isomerization of trans-SG was mediated by ultraviolet light or sunlight, our findings serve as reference for controlling photoisomerization in drug discovery and for the clinical use of Heshouwu and stilbene-related medications.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81403126 and 81503350), the National Key Technology R&D Program (No. 2015ZX 09501-004-001-008), China’s Post-doctoral Science Fund (No. 2016M590065), the National TCM Industry Science and Technology Program (No. 201507004-04), Beijing Nova Program (No. Z16111000490000), and the Beijing Natural Science Foundation (No. 7152142).

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Authors and Affiliations

  1. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China

    Chunyu Li, Ming Niu, Zhaofang Bai, Congen Zhang, Yanling Zhao, Ruiyu Li, Can Tu, Yakun Meng, Zhijie Ma, Wuwen Feng, Jinfa Tang & Jiabo Wang

  2. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China

    Chunyu Li

  3. Integrative Medical Center, 302 Military Hospital, Beijing, 100039, China

    Jing Jing, Yun Zhu & Xiaohe Xiao

  4. Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Zhijie Ma

  5. Diagnosis and Treatment Center for Non-infectious Diseases, 302 Military Hospital, Beijing, 100039, China

    Zhengsheng Zou

  6. Beijing Union University, Beijing, 100101, China

    Jinjie Li & Xiaoya Shang

  7. Shanxi University of Traditional Chinese Medicine, Taiyuan, 030619, China

    Huifang Li

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  1. Chunyu Li
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Correspondence to Xiaohe Xiao or Jiabo Wang.

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Li, C., Niu, M., Bai, Z. et al. Screening for main components associated with the idiosyncratic hepatotoxicity of a tonic herb, Polygonum multiflorum. Front. Med. 11, 253–265 (2017). https://doi.org/10.1007/s11684-017-0508-9

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