Modulation of Antitumor Immunity and the Tumor Microenvironment by Scutellaria barbata D. Don: A Scoping Review and Network Pharmacology Analysis.

Scutellaria barbata D. Don (SBD) has been widely investigated for antitumor activity, but its immune- and tumor microenvironment (TME)-related mechanisms remain fragmented. This study synthesized preclinical evidence on SBD and contextualized the findings using network pharmacology. A scoping review was conducted according to established scoping review methodology and PRISMA-ScR guidance. Preclinical in vitro and in vivo cancer studies published between January 2016 and December 2025 were searched in PubMed, Embase, CENTRAL, and OASIS. Network pharmacology analysis was performed using TCMSP, SwissTargetPrediction, ImmPort, GeneCards, STRING, Cytoscape, MCODE, DAVID, GO, and KEGG analyses. Fifty-six preclinical studies were included. SBD extracts, fractions, polysaccharides, diterpenoids, flavonoids, and isolated constituents suppressed cancer cell proliferation, induced cell-cycle arrest, promoted apoptosis and ferroptosis, modulated autophagy, induced endoplasmic reticulum stress-associated cell death, inhibited migration, invasion, angiogenesis, and metastasis, and enhanced chemosensitivity across diverse cancer models. Immune- and TME-related effects included activation of natural killer cells and CD8+ T cells, reduction in regulatory T cells, T helper 17 cells, myeloid-derived suppressor cells, and M2-like tumor-associated macrophage polarization, modulation of cytokine and inflammatory signaling, and regulation of epithelial-mesenchymal transition, matrix remodeling, angiogenesis, and metastatic niche formation. Network pharmacology identified 32 active candidate compounds, 408 predicted targets, and 152 immune/TME-overlapping targets. Protein-protein interaction and enrichment analyses highlighted AKT1, TNF, SRC, EGFR, and BCL2 as candidate hub targets and implicated PI3K-Akt, MAPK, Ras, EGFR tyrosine kinase inhibitor resistance, and proteoglycans in cancer. SBD-derived interventions showed antitumor, immunomodulatory, and TME-remodeling activities across diverse preclinical models. The integrated findings identify recurrent biological processes and candidate molecular targets, while differences in preparation, chemical characterization, dose, and experimental design limit direct comparison across studies. This framework supports further mechanistic, pharmacokinetic, and translational evaluation of chemically characterized SBD preparations and candidate compounds.