Novel myostatin inhibition by Acacia farnesiana: A network pharmacology workflow decoding its multi-target mechanism in sarcopenic obesity

Sarcopenic obesity (SO) represents a multifaceted metabolic disorder characterized by the pathological coexistence of skeletal muscle atrophy and dysfunctional adiposity, leading to severe metabolic and functional impairments. Myostatin, a key negative regulator of myogenesis, has emerged as a critical therapeutic target for counteracting muscle atrophy associated with SO. In this study, we deployed an integrative network pharmacology strategy to elucidate the pharmacokinetic profiles and therapeutic efficacy of Acacia farnesiana-derived bioactive agents, specifically palmitic acid and α-terpineol, as putative myostatin antagonists. The chemical constituents of A farnesiana were screened using various cheminformatics databases, followed by an evaluation of their pharmacokinetic and drug-likeness properties through SwissADME and ProTox-II. In silico target prediction, conducted using Swiss Target Prediction, was synergized with gene-disease associations from Gene Cards and Online Mendelian Inheritance in Man. Protein-protein interaction networks were constructed using STRING and visualized via Cytoscape, delineated core molecular targets implicated in myostatin signaling. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway investigation shows interactions between the identified bioactives and sarcopenia-associated signaling pathways, including myofiber regeneration, lipid metabolism, and oxidative stress response. Molecular docking provided structure-based support for the interaction between α-terpineol and estrogen receptor α, consistent with estrogen receptor 1-related findings from network pharmacology analyses, suggesting potential relevance to SO-related signaling pathways. This investigation shows the potential of A farnesiana-derived compounds in modulating muscle-related pathways and mitigating SO, providing a foundation for future preclinical and clinical investigations.