Construction and Application of Liver Injury Risk Prediction Model of Chinese Medicinals based on Indirect Toxicity
10.13288/j.11-2166/r.2023.17.008
- VernacularTitle:基于间接毒性认知的中药肝损伤风险预测模式的构建及应用
- Author:
Guangdi MU
1
;
Ming NIU
1
;
Yunjuan GAO
1
;
Chengzhao WU
1
;
Fei TANG
1
;
Xu ZHAO
1
;
Xiaoyan ZHAN
1
;
Zhaofang BAI
1
;
Yuming GUO
1
;
Xiaohe XIAO
1
Author Information
1. Fifth Medical Center of Chinese PLA General Hospital， Beijing， 100039
- Publication Type:Journal Article
- Keywords:
indirect toxicity;
drug-induced liver injury;
Chinese compound formula;
risk prediction
- From:
Journal of Traditional Chinese Medicine
2023;64(17):1763-1770
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore and establish the liver injury risk prediction model of indirect toxicity of Chinese medicinals under the condition of compound formulas， and provide new ideas and methods for the study of evaluation of liver injury of Chinese medicinals based on indirect toxicity. MethodsTaking Buguzhi （Fructus Psoraleae） pre-parations as model drug， the combined Chinese medicinals with Buguzhi （Fructus Psoraleae） of high frequency are screened out， and their components and action targets were obtained through TCMSP， TCMIP and PharmMapper databases. The association strength value and risk value of Chinese medicinals that acted on the nuclear factor κB （NF-κB） pathway were analyzed. For those having greater values than the median association strength value and risk value were regarded as indirect Chinese medicinals of liver injury risk. In this way， a prediction model of liver injury risk of Chinese medicinals was constructed based on immune activation-related indirect liver injury process （taking NF-κB pathway as an example）. And verification of the prediction model was performed using Heshouwu （Radix Polygoni Multiflori） preparations. ResultsThe prediction model of liver injury risk based on important immunoactivated pathway （taking NF-κB pathway as an example） found that Yinyanghuo （Herba Epimedii） （association strength value = 0.18， risk value = 0.25） was a Chinese medicinal with potential risk of indirect liver injury within Buguzhi （Fructus Psoraleae） prepartions， which may increase the risk of liver injury by positively regulating Bruton's tyrosine kinase （Btk） and protein kinase C theta （PKCθ） on NF-κB pathway. Further verification of prediction model by Heshouwu （Radix Polygoni Multiflori） preparations showed that Buguzhi （Fructus Psoraleae） （association strength value = 0.25， risk value = 0.33） and Tusizi （Semen Cuscutae） （Semen Cuscutae， association strength value = 0.34， risk value = 0.33） may increase the liver injury risk of Heshouzu. ConclusionThe liver injury risk prediction model of indirect toxicity of Chinese medicinals has been constructed in this study， providing metho-dological reference for the identification of Chinese medicinals of indirect liver injury risk under the condition of compound formulas.
