Wu, Qihui published the artcileIn silico identification and mechanism exploration of hepatotoxic ingredients in traditional Chinese medicine, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is hepatotoxic ingredient traditional Chinese medicine; consensus model; hepatotoxicity mechanism; herb induced liver injury; in silico; traditional chinese medicine.
Backgrounds and Aims: Recently, a growing number of hepatotoxicity cases aroused by Traditional Chinese Medicine (TCM) have been reported, causing increasing concern. To date, the reported predictive models for drug induced liver injury show low prediction accuracy and there are still no related reports for hepatotoxicity evaluation of TCM systematically. Addnl., the mechanism of herb induced liver injury (HILI) still remains unknown. The aim of the study was to identify potential hepatotoxic ingredients in TCM and explore the mol. mechanism of TCM against HILI. Materials and Methods: In this study, we developed consensus models for HILI prediction by integrating the best single classifiers. The consensus model with best performance was applied to identify the potential hepatotoxic ingredients from the Traditional Chinese Medicine Systems Pharmacol. database (TCMSP). Systems pharmacol. analyses, including multiple network construction and KEGG pathway enrichment, were performed to further explore the hepatotoxicity mechanism of TCM. Results: 16 single classifiers were built by combining four machine learning methods with four different sets of fingerprints. After systematic evaluation, the best four single classifiers were selected, which achieved a Matthews correlation coefficient (MCC) value of 0.702, 0.691, 0.659, and 0.717, resp. To improve the predictive capacity of single models, consensus prediction method was used to integrate the best four single classifiers. Results showed that the consensus model C-3 (MCC = 0.78) outperformed the four single classifiers and other consensus models. Subsequently, 5,666 potential hepatotoxic compounds were identified by C-3 model. We integrated the top 10 hepatotoxic herbs and discussed the hepatotoxicity mechanism of TCM via systems pharmacol. approach. Finally, Chaihu was selected as the case study for exploring the mol. mechanism of hepatotoxicity. Conclusion: Overall, this study provides a high accurate approach to predict HILI and an in silico perspective into understanding the hepatotoxicity mechanism of TCM, which might facilitate the discovery and development of new drugs.
Frontiers in Pharmacology published new progress about Bupleurum. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem