Magnolol-encapsulated PLGA nanoparticles attenuate inflammatory responses and oxidative stress in human peritoneal macrophages isolated from patients with cirrhosis

In cirrhosis, pathological translocation of gut bacteria disrupts immune balance and promotes spontaneous bacterial peritonitis. Peritoneal macrophages (PMs) play an important role in resolving peritoneal inflammation and controlling bacterial infections. However, their regulatory function can be impaired under cirrhotic conditions. Considering the anti-inflammatory and antioxidant properties of the natural compound magnolol, we hypothesized that it may exert these effects on human PMs. Moreover, encapsulation of magnolol into poly(lactic- co -glycolic acid) nanoparticles (PLGA-NPs) was expected to enhance its therapeutic potential. Herein, PMs were isolated from ascites of decompensated cirrhotic patients, stimulated with lipopolysaccharide (LPS), and exposed to magnolol-PLGA-NPs. Treated cells were analyzed using flow cytometry, fluorescence microscopy, ELISA, western blotting, and the CellROX Deep Red assay to check cellular uptake, inflammatory responses and oxidative stress. The results of the study indicated that encapsulation of magnolol into PLGA NPs improved its biocompatibility. Moreover, a robust uptake of labeled magnolol-PLGA-NPs by PMs was indicated. Upon LPS stimulation, treatment with magnolol-PLGA-NPs demonstrated both anti-inflammatory and antioxidant effects. They significantly suppressed TNF-α and IL-6 release, while preserving IL-10 levels, which may contribute to maintaining a balanced immune response. Treatment with magnolol-PLGA-NPs was also associated with reduced ERK1/2 and p38 phosphorylation, suggesting that modulation of MAPK signaling may contribute to the observed anti-inflammatory effects. Additionally, they significantly reduced oxidative stress in stimulated cells. Altogether, these results indicate that magnolol-encapsulated PLGA NPs exhibit anti-inflammatory and antioxidant effects in stimulated human PMs.