Investigating the Mechanisms of Prunella vulgaris against Acute Lymphoblastic Leukemia through Network Pharmacology and Experimental Validation

Objective:
This study investigates the underlying mechanisms
of Prunella vulgaris on apoptosis in
acute lymphoblastic leukemia (ALL) cells using an integrated approach
that combines network pharmacology, molecular docking, and cellular
experiments. Methods: Active ingredients of P. vulgaris and their potential targets were obtained from public databases,
along with target genes associated with ALL. Intersecting targets
were identified and analyzed through protein–protein interaction
(PPI) network analysis to screen for hub genes. Gene Ontology (GO)
and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment
analyses are conducted on the common targets. A network linking P. vulgaris, its active components, targets, and
KEGG pathways is constructed to identify key bioactive components.
Molecular docking is performed to assess the binding affinities between
the active compounds and core targets. Finally, in vitro experiments
validate the predictions derived from network pharmacology. Results:
PPI analysis identified five hub genes of P. vulgaris against ALL: CASP3, TNF, IL6, TP53, and AKT1. GO and KEGG analyses
reveal that the mechanisms primarily involve the regulation of apoptotic
signaling pathways, Bcl-2 family protein complexes, the PI3K/AKT and
p53 pathway. Network analysis indicates that quercetin acts as a central
active component of P. vulgaris against
ALL. Molecular docking revealed potent binding affinities of quercetin
toward all five core targets. Cellular experiments further confirm
that quercetin inhibits the proliferation of ALL cells and induces
mitochondrial pathway-mediated apoptosis, potentially through the
modulation of the PI3K/AKT and p53 pathways. Conclusion: This study
reveals that quercetin, a key active ingredient of P. vulgaris, mediates its anti-ALL activity by modulating
the PI3K/AKT/p53 axis while inducing mitochondrial apoptosis. These
findings provide reliable experimental evidence for utilizing P. vulgaris in the treatment of ALL.