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

被引：69

作者：

Li, Chunyu ^{[1
,2
,3
]}

Niu, Ming ^{[1
]}

Bai, Zhaofang ^{[1
]}

Zhang, Congen ^{[1
]}

Zhao, Yanling ^{[1
]}

Li, Ruiyu ^{[1
]}

Tu, Can ^{[1
]}

Li, Huifang ^{[8
]}

Jing, Jing ^{[4
]}

Meng, Yakun ^{[1
]}

Ma, Zhijie ^{[1
,5
]}

Feng, Wuwen ^{[1
]}

Tang, Jinfa ^{[1
]}

Zhu, Yun ^{[4
]}

Li, Jinjie ^{[7
]}

Shang, Xiaoya ^{[7
]}

Zou, Zhengsheng ^{[6
]}

Xiao, Xiaohe ^{[4
]}

Wang, Jiabo ^{[1
]}

机构：

[1] 302 Mil Hosp, China Mil Inst Chinese Med, Beijing 100039, Peoples R China

[2] Chinese Acad Med Sci, Inst Med Plant Dev, Beijing 100193, Peoples R China

[3] Peking Union Med Coll, Beijing 100193, Peoples R China

[4] 302 Mil Hosp, Integrat Med Ctr, Beijing 100039, Peoples R China

[5] Capital Med Univ, Beijing Friendship Hosp, Beijing 100050, Peoples R China

[6] 302 Mil Hosp, Diag & Treatment Ctr Noninfect Dis, Beijing 100039, Peoples R China

[7] Beijing Union Univ, Beijing 100101, Peoples R China

[8] Shanxi Univ Tradit Chinese Med, Taiyuan 030619, Peoples R China

来源：

FRONTIERS OF MEDICINE | 2017年 / 11卷 / 02期

基金：

北京市自然科学基金; 中国国家自然科学基金;

关键词：

Polygonum multiflorum; idiosyncratic hepatotoxicity; metabolomics; stilbene; cis-trans isomerization; INDUCED LIVER-INJURY; NITRIC-OXIDE; COMBRETASTATIN; ARGININE; TUBULIN; LIPOPOLYSACCHARIDE; RESVERATROL; METABOLISM; POLYAMINES; MEDICINE;

D O I：

10.1007/s11684-017-0508-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-beta-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.

引用

页码：253 / 265

页数：13

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