Development of an in vitro screening method for idiosyncratic hepatotoxic components in traditional Chinese medicine: a case study with Epimedii Folium and Psoraleae Fructus
10.16438/j.0513-4870.2023-0928
- VernacularTitle:一种中药相关特异质肝损伤成分筛选的体外评价方法的建立: 以补骨脂和淫羊藿为例
- Author:
Ying-ying LI
1
;
Meng-meng LIN
1
;
Bo CAO
1
;
Ying LI
1
;
Jing XU
1
;
Xiao-he XIAO
2
;
Guo-hui LI
1
;
Chun-yu LI
1
Author Information
1. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
2. China Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
- Publication Type:Research Article
- Keywords:
italic>Epimedii Folium;
italic>Psoraleae Fructus;
idiosyncratic drug-induced liver injury;
hepatotoxicity component;
immune-promoting hepatotoxicity component
- From:
Acta Pharmaceutica Sinica
2024;59(3):621-632
- CountryChina
- Language:Chinese
-
Abstract:
Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.
