Reveal the pharmacodynamic substances and mechanism of an edible medicinal plant Platycodonis radix inhibits tumor

• 61 compounds were identified in Platycodonis radix (PR), among which 29 compounds could be absorbed into blood. • PR suppresses mouse melanoma proliferation by inhibiting infiltration of M2 macrophages. • PR inhibits the polarization of M2 macrophages, mitochondrial function of M2 macrophages, tumor-promoting functions of M2 macrophages. • PR promote the ubiquitin-mediated degradation of JAK2. Accumulating evidence suggests that M2-polarized tumor-associated macrophages (TAMs) play a crucial role in cancer progression, making them a promising target for therapy. This study explored the molecular mechanisms by which Platycodon grandiflorum regulates M2 polarization of TAMs to exert anti-tumor effects. UPLC-MS identified the chemical composition and blood-absorbed components. Immunohistochemistry and Western blot detected TAM infiltration and proliferation pathways, while q-RT-PCR measured M2 macrophage marker expression. Our findings showed that PR reduces melanoma weight, inhibits the mTOR pathway, and suppresses M2-polarized macrophages. PR downregulates JAK2 and p-STAT3, promotes JAK2 degradation, and enhances ubiquitination. Molecular docking indicated strong affinities between Platycodin D components and JAK2/STAT3, highlighting PR’s potential in regulating TAMs and offering new clinical insights.