Abstract:In order to clarify the potential anti-fatigue mechanism of Phyllanthus emblica L., a systematic investigation was conducted based on network pharmacology and molecular docking. The active chemical constituents of Phyllanthus emblica L. were systematically screened using the TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) database, and their potential targets were predicted with the SwissTarget Prediction online tool. A fatigue-related disease target set was constructed by integrating data from multiple databases, including DrugBank, DisGeNET, GeneCards, and DigSee. The active component targets of Phyllanthus emblica L. were mapped onto the fatigue-related target set to identify shared effect targets, and a protein-protein interaction (PPI) network was subsequently constructed based on the STRING database. The topological properties of the PPI network were analyzed using Cytoscape software to identify potential core targets. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the core targets were performed using the David database to elucidate their core biological functions and key regulatory pathways. Finally, molecular docking validation was conducted using AutoDock Vina and PyMOL software. The results revealed that 18 active constituents of Phyllanthus emblica L. were obtained, corresponding to 144 disease-related targets, while 1,431 fatigue-related targets were identified, yielding 47 constituent-disease intersection targets, from which 7 key active constituents and 7 core targets were screened. GO functional enrichment analysis of biological processes indicated that these core targets were mainly involved in phosphorylation, signal transduction, and negative regulation of apoptotic processes. KEGG pathway enrichment analysis demonstrated that the principal pathways included the PI3K-Akt signaling pathway, endocrine resistance, and the MAPK signaling pathway. Molecular docking validation confirmed stable interactions and high binding energies between the active constituents and their targets. These findings suggest that Phyllanthus emblica L. exerts its anti-fatigue effects primarily through constituents such as quercetin, luteolin, kaempferol, and ellagic acid, which act on targets including EGFR, ESR1, and AKT1, thereby regulating the PI3K-Akt, endocrine resistance, and MAPK signaling pathways via mechanisms encompassing energy metabolism reprogramming, mitochondrial quality control, oxidative-antioxidative balance, cellular damage repair, autophagic flux regulation, and the neuro-endocrine-immune network. The results provide a reference for further experimental investigations of Phyllanthus emblica L. and the development of medicine-food homology health products.