Exploring the Role of Alpinia officinarum against Acute Myeloid Leukemia using Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation

Abstract

Background:Alpinia officinarum, a member of the Zingiberaceae family, is native to East Asia. It possesses various properties, including antineoplastic effects, but the molecular mechanism underlying its inhibition of acute myeloid leukemia (AML) remains unclear. This study explored the biological mechanisms and pharmacological effects of Alpinia officinarum in AML through network pharmacology, molecular docking and molecular dynamics (MD) simulation. Methods: Active compounds were identified through a literature review and Dr. Duke’s database. Compounds were screened based on solubility, oral bioavailability (OB) and drug-likeness (DL) using SwissADME and Molsoft tools. Targets related to the identified compounds were acquired using SwissTargetPrediction, and AML targets were extracted from DisGeNET, OMIM and GeneCards. Common targets of the active compounds and AML were further analyzed via gene ontology (GO) and pathway enrichment using ShinyGO, followed by the protein–protein interaction (PPI) through STRING and Cytoscape to elucidate key targets. Molecular docking and dynamics simulation were employed to find a lead compound. Results: Eleven potential active compounds and six key targets were identified. The targets were enriched in pathways such as central carbon metabolism in cancer and the PI3K-Akt signaling pathway. Molecular docking revealed that Alpinin A had a high affinity for the six key targets (BCL2, AKT1, PIK3CA, ABL1, TERT and FLT3). Furthermore, MD simulation demonstrated the stability of the AKT1-Alpinin A complex which showed the best docking score among other active compounds. Conclusion: Our study indicates that Alpinin A may serve as a promising agent against AML, highlighting its potential for further pharmacological investigation.