Computational Multi-Target Profiling of Lupeol Against Cardiometabolic Diseases: An Integrated Docking, Network Pharmacology, and Molecular Dynamics Approach

Velusamy, Pavithra; Rani, S.; Ariharasivakumar, G.

doi:10.48309/ajca.2026.562524.1984

Computational Multi-Target Profiling of Lupeol Against Cardiometabolic Diseases: An Integrated Docking, Network Pharmacology, and Molecular Dynamics Approach

Document Type : Original Research Article

Authors

Pavithra Velusamy ¹

S. Rani ¹

G. Ariharasivakumar ²

¹ Department of Pharmacy, Annamalai University, Chidambaram, Tamil Nadu, India

² Department of Pharmacology, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, India

https://doi.org/10.48309/ajca.2026.562524.1984

Abstract

Cardiometabolic diseases (CMDs), including type 2 diabetes, obesity, and cardiovascular disorders, share interlinked pathogenic mechanisms involving chronic inflammation, insulin resistance, oxidative stress, and endothelial dysfunction. Multi-target agents derived from natural compounds offer promising therapeutic avenues for CMD management. Lupeol, a pentacyclic triterpenoid, has demonstrated diverse bioactivities, yet its mechanistic relevance in CMDs has not been comprehensively elucidated.We aimed to elucidate the multitarget pharmacological potential of lupeol against CMDs through an integrated computational approach encompassing network pharmacology, computational docking, and dynamic simulation.Lupeol- and CMD-associated targets were retrieved from various databases and analyzed via protein–protein interaction (PPI) analysis via Cytoscape. Functional enrichment was performed using DAVID and Metascape. Drug-likeness and toxicity were assessed through SwissADME and ADMETlab 2.0. Binding affinities were evaluated using computational docking, followed by MD simulations and specific tissue expressions to validate complex stability. A total of 179 shared targets were identified, with STAT3, MAPK3, ESR1, EGFR, and CXCR4 emerging as key hub genes. GO and KEGG enrichment highlighted significant involvement in PI3K–Akt, MAPK, JAK–STAT, and AGE–RAGE regulatory pathways. Lupeol exhibited strong interaction energies (–9.08 to –6.08 kcal/mol) and stable interactions with major CMD targets. ADME-Tox profiling demonstrated its oral bioavailability, BBB permeability, and low toxicity risk. MD simulations showed stable protein–ligand conformations under near-physiological conditions. Collectively, these findings highlight lupeol as a promising multi-target lead compound for cardiometabolic disease management and provide a robust computational foundation for its future experimental and translational evaluation.

Graphical Abstract

Keywords

Lupeol

Cardiometabolic diseases

Network pharmacology

Molecular docking

Molecular dynamics

PI3K-Akt signaling

Subjects

Analytical chemistry

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