Effects of synthetic silymarin-PLGA nanoparticles on M۲ polarization and inflammatory cytokines in LPS-treated murine peritoneal macrophages

Objective(s): Silymarin (SM) is a natural antioxidant compound with good anti-inflammatory effects, but its poor water solubility restricts its usage. Today, nanomaterial compounds (such as PLGA Poly D, L-lactic-co-glycolic acid) can provide a proper drug delivery system and help improve the accessibility of bioactive compounds to cells and tissues. Materials and Methods: In this study, PLGA nanoparticles (NPs) containing SM (SM-PLGA) were synthesized and characterized and their biological effects were evaluated on M۲ macrophage polarization to regulate inflammation. SM-PLGA NPs were fabricated by the oil in water emulsion (O/W) method. Macrophages (MQs) were isolated from mouse peritoneum by the cold RPMI lavage protocol. Primary mouse MQ cells were treated by SM and SM-PLGA NPs and then stimulated with lipopolysaccharide (LPS). M۲ polarization was evaluated by measurements of cytokine secretion levels (TNF-α, IL۱-β, and IL-۱۰), flow cytometry markers (F۴/۸۰, CD۱۱b, CD۳۸, and CD۲۰۶), and the expression of specific proteins (M۲ Ym۱ and Fizz۱).Results: SM-PLGA characterization showed that NPs were fabricated in the desired form. SM and SM-PLGA decreased pro-inflammatory cytokines (TNF-α and IL۱-β) and increased IL۱۰ as an anti-inflammatory cytokine. On the other hand, the M۲-associated markers and proteins increased following treatment with SM and SM-PLGA. Post-hoc analysis indicated that these changes were more pronounced in the SM-PLGA group.Conclusion: This study revealed that SM-PLGA could markedly promote M۲ polarization, thereby providing a valuable medical approach against sepsis and septic shock.

کلیدواژه ها:

Cytokines ، Nanoparticles ، PLGA compound ، Peritoneal macrophages ، Silymarin