Anti-inflammatory effects of magnolol-encapsulated nanoparticles on peritoneal macrophages isolated from cirrhotic patients

Introduction: Cirrhosis is a chronic liver condition characterized by persistent inflammation and fibrosis, which contributes to a significant mortality rate worldwide. Magnolol (MAG) is a polyphenolic compound derived from the bark of Magnolia officinalis, possessing various biological properties, including anti-inflammatory effects. However, the effectiveness of MAG is challenged by its poor biocompatibility and cytotoxicity. To address these limitations, nanoparticle-based drug delivery systems offer a promising strategy to reduce MAG cytoxicity.

Objectives: The present study investigates the anti-inflammatory effects of MAG-encapsulated nanoparticles (NPs) on peritoneal macrophages (PMs) isolated from patients with liver cirrhosis.

Methodology: PMs, freshly isolated from the ascitic fluid of cirrhotic patients, were stimulated with lipopolysaccharide (LPS), and treated with MAG-encapsulated poly (lactideco-glycolic acid) (PLGA), Eudragit S100 or a combination of both (PLGA/ Eudragit S100-50/50). Following a 24 h incubation, the expression levels of cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10), were quantified using ELISA. Furthermore, cell lysates were collected for western blotting to assess the expression levels of phosphorylated extracellular signal-regulated kinase (p-ERK1/2) and phosphorylated p38 MAPK (p-p38). The cellular uptake of labeled PLGA-MAG was evaluated by flow cytometry and fluorescent microscopy.

Results: Encapsulation of MAG into NPs enhances its biocompatibility by reducing cytotoxicity and modulating inflammatory responses in LPS-stimulated human PMs. Specifically, PLGA-MAG effectively attenuates inflammation in LPS-stimulated PMs by suppressing pro-inflammatory cytokines (TNF-α and IL-6), while preserving IL-10 levels, which may contribute to maintaining a balanced immune response. Furthermore, MAG-encapsulated NP suppressed MAPK signalling by downregulating the phosphorylation of ERK1/2 and p38 proteins. Moreover, flow cytometry and fluorescent microscopy indicated that over 90% of cells uptake the labeled PLGA-MAG ([Fig. 1] [2]).

Fig. 1  

Fig. 2  Effect of magnolol (MAG)-encapsulated nanoparticles on the phosphorylation levels of MAPK pathway in LPS-stimulated peritoneal macrophages. Representative immunoblots and quantitative analysis for p-ERK1/2 (A), and p-p38 (B) in whole cell lysates of LPS-stimulated peritoneal macrophages. Here, β-actin was used as a loading control. n=3-5 patients with liver cirrhosis. The results are presented as M±SEM.

Conclusion: For the first time the anti-inflammatory effects of Magnolol were demonstrated in human peritoneal macrophages. Moreover, encapsulating MAG in NPs modulates its potential cytotoxicity. Thus, MAG-encapsulated PLGA nanoparticles may represent a promising therapeutic approach against peritoneal inflammation in cirrhotic patients.

Publication History

Article published online:
04 September 2025