Firdayani, Putri Hawa Syaifie, Siska Andrina Kusumastuti, Muthia Rahayu Iresha, Wirawan Adikusuma, Dhecella Winy Cintya Ningrum, Etik Mardliyati, Ayu Masyita, Ariza Yandwiputra Besari, Fathir Azzaki Iradata, Lucy Arianie
Background: Emodin exhibits various pharmacological activities, including hepatoprotective effects. However, its clinical application is limited by poor absorption and low oral bioavailability. This study aimed to optimize emodin through benzoylation and to assess the hepatoprotective potential of the resulting derivatives integrating bioinformatics and in vitro methods. Methods: We conducted network pharmacology, molecular docking and molecular dynamics (MD) simulations to predict potential targets and interactions of benzoylated emodin derivatives. The derivatives were synthesized and evaluated for cytotoxicity using the MTT assay. The hepatoprotective effects were assessed in vitro using a paracetamol-induced HepG2 cell injury model. Results: Network pharmacology analysis and gene expression profiling identified four major targets―HSP90AA1, MAPK14, RELA, and PRKACA―as key liver disease-related targets of emodin and its derivatives. Molecular docking study revealed that the benzoylated emodin derivatives exhibited generally lower (more negative) binding energies compared to emodin across all four targets. MD simulations confirmed that the complex RELA with these derivatives is more stable than with emodin. These findings were consistent with in vitro assays, emodin and its derivatives increased cell viability or protected the cells up to 60—70%. Conclusion: This study provides a comprehensive evaluation of benzoylated emodin derivatives as potential hepatoprotective agents. The findings suggest that these derivatives exhibit binding affinity toward important targets related to cirrhosis, reduced toxicity to cells, and enhanced the efficacy in protecting the liver in vitro liver injury model. © the Author(s).
Research Center for Vaccine and Drugs, National Research and Innovation Agency (BRIN), Raya Bogor St No 32, Cibinong, Indonesia; Center of Excellence Life Sciences, Nano Center Indonesia, Tangerang Selatan, Indonesia; Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency (BRIN), Raya Bogor St No 32, Cibinong, Indonesia; Research Center for Computing, Research Organization for Electronics and Informatics, National Research and Innovation Agency (BRIN), Raya Bogor St No 32, Cibinong, Indonesia; Research Center for Nanotechnology System, National Research and Innovation Agency (BRIN), Tangerang Selatan, Indonesia; Chemistry Department, Faculty of Mathematics and Natural Sciences, Jakarta State University (UNJ), Jakarta, Indonesia
Research at a Glance
Register to unlock
Topics & SDG Alignment
Register to unlock
Collaboration
Register to unlock
Author Profile (Selected)
Register to unlock
References Overview
Register to unlock
Journal & Source
Register to unlock
Metadata & Integrity
Register to unlock