Predicting the mechanism of action of Silymarin —Pueraria lobata—Prednisolone combination in the treatment of alcoholic liver disease based on network pharmacology and molecular docking.
Authors: Qin Jiayi , Li Zhuan 
Published: January 2024

Objective: To predict the key targets, active ingredients, and pathways of action of Silymarin-Pueraria lobata- Prednisolone combination for the treatment of Alcoholic Liver Disease (ALD) based on the web-based pharmacology and molecular docking approach, and to determine the biological processes and molecular functions of its action. Methods: Several databases including TCMSP, Pharm Mapper, PubChem, TTD, Drugbank, OMIM and UniProt were used to identify the targets of Silymarin, Pueraria lobata and Prednisolone for the treatment of ALD. The main targets of the combination of Chinese and Western medicines were identified by Venn diagram analysis. Protein interaction networks were constructed and information on biological processes and molecular functions was obtained with the help of the STRING web site. Target genes were visualised using the Cytoscape software. Potential targets were analysed using the Metascape website. Molecular docking was performed with the key target genes screened. This was done to confirm the drug compounds identified in the enrichment results.Results: A total of 95 targets were identified in the combination therapy of Silymarin-Pueraria lobata-Prednisolone for the treatment of ALD. The key targets include ALB, IL6, and TNF. When used for treating ALD, the therapy primarily acts on the following functions: Chemical carcinogenesis - receptor activation, Neuroactive ligand-receptor interaction, Pathways in cancer, and Calcium signaling pathway, among others. In the treatment of ALD, 161 pathways are primarily targeted, including those involved in blood circulation, cellular response to organic cyclic compounds, cationic acid, and various other pathways. These pathways include response to organic cyclic compounds, circulatory system processes, nuclear receptor activity, ligand-activated transcription factor activity, neurotransmitter activity, and neurotoxicity, as well as neurotransmitter receptor activity, and 157 other molecular functions for the combination therapy of ALD. Research using molecular docking techniques indicates that the combination therapy of Silymarin, Pueraria lobata and Prednisolone is effective in the treatment of ALD due to the high affinity observed between the core target proteins and the active ingredients of the drug.Conclusion: The primary objective of combining Silymarin, Pueraria lobata, and Prednisolone therapy for ALD was screened and confirmed via network pharmacology and molecular docking. The analysis also predicted the possible mechanism of action for the combination of Chinese and Western medicines in ALD treatment, laying a solid foundation for further development of Silymarin-Pueraria lobata-Prednisolone therapy. Providing a theoretical framework for the subsequent experimentation and clinical validation of Silymarin-Pueraria lobata-Prednisolone combination therapy for ALD. Concurrently, it serves as a reference for enhancing network pharmacology and molecular docking methodologies when predicting the mechanism of actions of combined Chinese and Western therapies for various diseases.