The use of silymarin-encapsulated liposome nanoparticles (SLNPs) improved copper toxicity and neurobehavioral abnormalities in a Wilson disease (WD) animal model, according to a study published in Molecules.

Significant reductions in liver enzymes, including aspartate transaminase, alanine transaminase, alkaline phosphatase, and total bilirubin, were observed in animals treated with SLNPs compared to those of animals who were not treated (P =.0003, P =.0007, P =.0083, and P =.002, respectively).

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“SLNPs proved to be an effective treatment for managing the phenotypic effects of copper toxicity,” the authors said.

Changes in performance on forced swim tests and Y maze tests were also observed between animals treated with SNLPs and those who did not receive treatment. The mean immobility period during the forced swim test decreased from 215 s for the untreated group to 155 s for the SNLP-treated group (P =.0004). In comparison, control rats had a mean of 130 s of immobility during the test. These results indicate potential mitigation of depression symptoms, according to the authors.

Results of the Y maze test showed a decrease in spatial memory from 82% in the control rats to 49% in the untreated WD rats (P =.0009). Treatment with SNLPs improved spatial memory to 70% (P =.006). Improved spatial memory is a marker of improved cognitive functioning.

“This in vivo study showed efficiency of the SLNPs against liver dysfunction and neurobehavioral changes caused by copper toxicity. Further investigations to analyze the effects of SLNPs on cytokines and oxidative stress are necessary and will be vital for the further assessment of these novel nanoparticles,” the authors said.

The study also investigated the use of zinc and zinc plus SLNPs (ZSLNPs) and found that the combination was more effective than zinc alone.

Silymarin was investigated in the study because it has previously been shown to be a useful medication for the treatment of liver diseases due to its antioxidant, anti-inflammatory, and antifibrotic properties. Its efficacy is decreased, however, due to poor oral bioavailability, so the use of liposome nanoparticles to encapsulate the silymarin was tested.

For the study, 35 female Wistar rats were tested and divided into 7 groups of 5 rats. One group served as the control group, while the other 6 groups received copper sulfate daily for up to 90 days to simulate the copper toxicity observed in WD. The treatment groups included the diseased (untreated), silymarin-treated, SLNP-treated, blank liposome nanoparticle-treated, zinc-treated, and ZSNLP-treated groups.


Maryam T, Rana NF, Alshahrani SM, et al. Silymarin encapsulated liposomal formulation: an effective treatment modality against copper toxicity associated liver dysfunction and neurobehavioral abnormalities in Wistar rats. Molecules. Published online February 3, 2023. doi:10.3390/molecules28031514