Screening and Validation of Active Ingredients in Sini Decoction by Combination Method of Pharmacophore Modeling and Molecular Docking

• Published in: Chinese herbal medicines Vol. 8; no. 2; pp. 126 - 132
• Main Authors: Chen, Lang-dong, Wang, Dong-yao, Cao, Yan, Zhu, Zhen-yu, Chai, Yi-feng
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.04.2016
• Subjects: activity screening; heart failure; molecular docking; pharmacophore model; Sini Decoction; 分子对接; 四逆汤; 有效成分; 活性化合物; 细胞存活率; 药效团; 虚拟筛选; 验证; heart failure; pharmacophore model; molecular docking; activity screening; Sini Decoction
• ISSN: 1674-6384; 2589-3610
• DOI: 10.1016/S1674-6384(16)60021-7

Objective To screen the active compounds in Sini Decoction showing the potential to inhibit tumor necrosis factor α（TNFα） to alleviate Doxorubicin（DOX）-induced heart failure. Methods A chemical database of Sini Decoction was constructed from literature research. The generated pharmacophore models based on TNF-α used to screen active ingredients of Sini Decoction in the database by Discovery Studio 2.5. Molecular docking by Autodock 4.2 was adopted to demonstrate the hit compounds＇ affinities with TNFα. Furthermore, DOX-induced heart failure model on H9c2 cell line was constructed and cell viability was detected by CCK-8 to validate the therapeutic effect of potential active compounds. Results The higenamine showed potential cardiovascular protective effect through virtual screening. And the activity was identified in vitro. Conclusion In this study, we found that higenamine may inhibit TNF-ɑ through virtual docking and validated that higenamine may have the potential of treatment for heart failure in the model of doxorubicin-induced myocardial toxicity to H9c2 cells.