Immunomodulatory Effect of the Ursolic Acid/Poly-β-cyclodextrin Complex in an Experimental Model of Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system, characterized by demyelination and inflammation. Although treatments are available, they have serious adverse effects and are expensive. Ursolic acid (UA) has anti-inflammatory and neuroprotective properties, but its low solubility hinders its application. This study developed and characterized a ursolic acid with poly-β-cyclodextrin (UA/pβCD) complex and evaluated its immunomodulatory potential in vitro and in vivo. Fourier transform infrared spectroscopy, thermal analyses, and phase solubility experiments confirmed the complexation. The complex improved UA solubility and thermal stability, reduced cytotoxicity in macrophage cell lines, and decreased nitric oxide production. In the experimental autoimmune encephalomyelitis (EAE) model, UA and UA/pβCD reduced neurological disability scores, indicating an attenuation of the inflammatory response. The complex group showed lower levels of IL-12p70 in the brain and spinal cord. These results indicate that the UA/pβCD complex is a promising strategy for the treatment of MS.

Keywords:
multiple sclerosis; experimental autoimmune encephalomyelitis; UA/pβCD complex; poly-β-cyclodextrin; ursolic acid