Network Pharmacology of Swietenolide from Swietenia mahagoni Jacq.: Putative Mechanisms Against Leukemia

Fitrawan Hernuza Pribadi; Sumardi Sumardi

doi:10.37311/jsscr.v8i1.36333

Network Pharmacology of Swietenolide from Swietenia mahagoni Jacq.: Putative Mechanisms Against Leukemia

Fitrawan Hernuza Pribadi, Sumardi Sumardi

Abstract

Leukemia is a type of cancer that can affect people of all ages and genders, and its cause is not yet known. This is exacerbated by an increasing trend, meaning that existing treatments are inadequate, therapy resistance, resulting in negatively impact for patients. The use of natural products can be a solution to this problem due to their multitarget effects. The use of swietenolide as a bioactive phytochemical from Swietenia mahagoni Jacq. can be used as an anti-leukemic agent. This study aims to explore the mechanism of swietenolide with target proteins as a treatment for leukemia using a network pharmacology approach. A predictive network depicting the relationship between swietenolide with leukemia was designed based on information collected from databases, namely Swiss Target Prediction (STP) version 2019, and DisGeNET version 2025. All databases accessed in October 2025. Identified overlapping targets related to both swietenolide with leukemia were crossed with information on biological processes (BPs) and molecular/signaling pathways using the ShinyGO and Cytoscape software. For the result, genes obtained from STP and DisGeNet, 111 and 438 genes, respectively, with the following results overlapping targets between swietenolide and leukemia gene targets produced 20 genes, with AKT1 showing the highest degree centrality score from the protein-protein interaction analysis results. Gene ontology from all genes showed biological processes related to apoptosis-multiple species and acute myeloid leukemia. AKT1 emerged as the top hub; AKT/mTOR signaling is implicated in Acute Myeloid Leukemia (AML) pathobiology. Inhibition of AKT1 expression is a key target that can reduce the proliferation and migratory activity of AML cells. As a result, this study successfully predicted the mechanism of action of swietenolide from mahogany seeds (Swietenia mahagoni Jacq.) using a network pharmacology analysis approach.

Keywords

Swietenolide; Swietenia mahagoni; Network Pharmacology; AKT1; mTOR pathway; Acute Myeloid Leukemia

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DOI: https://doi.org/10.37311/jsscr.v8i1.36333

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