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New incompatible pair of TCM: Epimedii Folium combined with Psoraleae Fructus induces idiosyncratic hepatotoxicity under immunological stress conditions |
Yuan Gao1,2, Zhilei Wang2,3, Jinfa Tang4, Xiaoyi Liu2, Wei Shi2,5, Nan Qin2,5, Xiaoyan Wang4, Yu Pang6, Ruisheng Li7, Yaming Zhang2, Jiabo Wang2, Ming Niu2(), Zhaofang Bai2(), Xiaohe Xiao8() |
1. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China 2. China Military Institute of Chinese Materia, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100039, China 3. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China 4. The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China 5. School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Jiangxi 330004, China 6. National Institutes for Food and Drug Control, Beijing 100050, China 7. Research Center for Clinical and Translational Medicine, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100039, China 8. Integrative Medical Centre, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100039, China |
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Abstract Epimedii Folium (EF) combined with Psoraleae Fructus (PF) is a common modern preparation, but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years. Zhuangguguanjiewan pills (ZGW), which contain EF and PF, could induce immune idiosyncratic liver injury according to clinical case reports and a nonhepatotoxic dose of lipopolysaccharide (LPS) model. This present study evaluated the liver injury induced by EF or PF alone or in combination and investigated the related mechanism by using the LPS model. Liver function indexes and pathological results showed that either EF or PF alone or in combination led to liver injury in normal rats; however, EF or PF alone could lead to liver injury in LPS-treated rats. Moreover, EF combined with PF could induce a greater degree of injury than that caused by EF or PF alone in LPS-treated rats. Furthermore, EF or PF alone or in combination enhanced the LPS-stimulated inflammatory cytokine production, implying that IL-1β, which is processed and released by activating the NLRP3 inflammasome, is a specific indicator of EF-induced immune idiosyncratic hepatotoxicity. Thus, EF may induce liver injury through enhancing the LPS-mediated proinflammatory cytokine production and activating the NLRP3 inflammasome. In addition, the metabolomics analysis results showed that PF affected more metabolites in glycerophospholipid and sphingolipid metabolic pathways compared with EF in LPS model, suggesting that PF increased the responsiveness of the liver to LPS or other inflammatory mediators via modulation of multiple metabolic pathways. Therefore, EF and PF combination indicates traditional Chinese medicine incompatibility, considering that it induces idiosyncratic hepatotoxicity under immunological stress conditions.
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Keywords
Epimedii Folium
Psoraleae Fructus
idiosyncratic hepatotoxicity
traditional Chinese medicine incompatibility
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Corresponding Author(s):
Ming Niu,Zhaofang Bai,Xiaohe Xiao
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Just Accepted Date: 31 January 2019
Online First Date: 27 March 2019
Issue Date: 02 March 2020
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