Pennogenin 3-O-β-Chacotrioside and Polyphyllin VI Modulate Macrophage Polarization-Associated Markers and Are Associated with Reduced CaL27 Viability

Paris polyphylla-derived steroidal saponins have potential immunomodulatory and antitumor activities, but their effects on macrophage phenotypes remain incompletely defined. Here, we examined pennogenin 3-O-β-chacotrioside (P3Oβ) and polyphyllin VI (PPVI) in THP-1-derived macrophages and CaL27 oral squamous cell carcinoma cells. In M0 macrophages, P3Oβ was associated with increased M1-related markers, whereas PPVI produced more limited marker changes. Transcriptomic analysis further identified enrichment of an NF-κB-associated transcriptional program after P3Oβ treatment. In M2 macrophages, both compounds shifted surface and transcriptional marker profiles toward a more M1-like pattern. After compound pretreatment and washout, non-contact co-culture with P3Oβ- or PPVI-pretreated macrophages reduced CaL27 viability and adherent-cell-associated crystal violet staining. These findings indicate that P3Oβ and PPVI modulate macrophage-associated phenotypic profiles and can be associated with reduced CaL27 viability after compound withdrawal, supporting further investigation of their macrophage-modulating effects in oral squamous cell carcinoma.