Evaluation of the immune-modulatory, anti-oxidant, proliferative, and anti-apoptotic effects of nano-silymarin on mesenchymal stem cells isolated from multiple sclerosis patients' adipose tissue sources

Abstract

Silymarin (SL) has a long history of use for the treatment of a variety of diseases, but several limitations, such as poor bioavailability and negligible solubility, have restricted its successful translation in a clinical setting. However, the nano-micelle delivery system is a highly reproducible method which capable of improving poor-water solubility and bioavailability of free-SL. Mesenchymal stem cells (MSCs) are multipotent cells proficient in tissue renewal and regeneration. MSCs have similar properties to SL including immunomodulatory, antioxidant, and neuroprotective effects. Here, we show that nano-SL (1 and 2.5) increased AD-MSCs proliferation and protected from apoptosis. Our findings indicated that the levels of anti-inflammatory agents including IL-10, IL-4, FOXp3 and TGF-B mRNA expression were significantly upregulated in nano-SL-treated MSCs along with downregulated mRNA expression of pro-inflammatory cytokines (IL-6, IL-17). We identified that nano-SL elevated the T-regulatory (Treg) population (1 and 2.5 µM) and superoxide dismutase activity (2.5 µM) while decreasing nitrite oxide content. Conclusively, combinatorial therapy by nano-SL and MSCs may be useful for MS patients who are receiving MSCs for treatment.

Keywords

• Nano-silymarin
• T regulatory cells
• Mesenchymal stem cells
• Immunoregulatory
• Multiple sclerosis
• Antioxidant