Anti-neuroinflammatory gold nanocomplex loading ursodeoxycholic acid following spinal cord injury

Abstract

Spinal cord injury (SCI) causes permanent nerve damage by disturbing axon regeneration from pro-inflammations and still remains a serious worldwide problem. Ursodeoxycholic acid (UDCA) has been reported that it can serve as an anti-neuroinflammatory drug such as Methylprednisolone (MP). However, the therapeutic effect of UDCA is limited due to its hydrophobic property. In this study, we aimed to investigate the anti-neuroinflammatory effects of gold nanoparticles (GNPs) loading UDCA (GNP-UDCA complex) following SCI. For this, we conjugated with β-cyclodextrin (β-CD) on the GNP's surface and included UDCA in β-CD by sonicating. We confirmed that the GNP-UDCA complex successfully synthesized. A mechanical SCI was imposed on rats and we injected GNP-UDCA complex three times after injury. After SCI, motor function and the lesions were significantly improved in the GNP-UDCA complex group than those in MP group and UDCA group. This complex significantly decreased pro-inflammatory cytokines and increased anti-inflammatory cytokines in terms of mRNA and protein levels than MP and UDCA. In addition, GNP-UDCA complex significantly suppressed the phosphorylation of extracellular signal-regulated kinase (p-ERK) and c-Jun N-terminal kinase (p-JNK) in the mitogen-activated protein kinase (MAPK) pathway than MP and UDCA. Finally, the complex significantly exhibited the expression of inducible nitric oxide synthase (iNOS). It also induced the expression of arginase-1 (Arg-1), anti-inflammatory marker, at the injured sites more than that in the saline group. In conclusion, this study demonstrates the anti-neuroinflammatory effects of GNP-UDCA complex in SCI and suggests that the GNP-UDCA complex can be an alternative drug system for SCI cases.