Immunomodulatory and antitumoral potentials of polyphenol-rich Salsola tetrandra leaf extract

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Abstract This study explored the influence of Salsola tetrandra leaf polyphenol-rich extract (STLPRE) on RAW 264.7 macrophage polarization and its potential antitumoral effects on transplanted mouse melanoma cells (B16). The phenolic contents and antioxidant activities of STLPRE were initially assessed. Furthermore, the immunomodulatory impact of STLPRE on RAW 264.7 cells and its in vitro and in vivoantitumoral effects against B16 cells were investigated. Exposing RAW 264.7 cells to STLPRE (10 and 30 µg/ml) upregulated conventional activated macrophage (M1) markers, including TNF-α, IL-1, IL-6, IL-12, Arg2, NO, and iNOS, with significant increases in NF-κB (p65) and MAPKs (ERK2, p38, JNK) activation. STLPRE also reduced M2 markers, decreasing Arg1 and CD206 mRNA expressions. Pro-inflammatory cytokine mRNA expression was less pronounced in STLPRE-treated macrophages than in LPS-stimulated cells. Notably, IL-1, IL-6, and IL-12 mRNA expressions in LPS-stimulated cells were approximately 60 %, 186 %, and 244 % higher than those in STLPRE-treated cells (30 µg/ml). In LPS-stimulated macrophages, STLPRE treatment significantly decreased nitric oxide (NO) production and M1 markers expression in a dose-dependent manner, concurrently inhibiting NF-κB phosphorylation. Interestingly, STLPRE or supernatant from STLPRE-treated macrophages reduced B16 viability in vitro and inhibited B16 tumor growth in C57BL/6 mice. This reduction in B16 tumor growth was associated with increased splenic mRNA expression of IFN-γ, IL-1, and IL-12 in STLPRE-treated mice. Our findings suggest that STLPRE represents a promising source of antitumoral biomolecules.

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