Protective Effects of Asiatic Acid Against Spinal Cord Injury-Induced Acute Lung Injury in Rats

Abstract

The biological effects of asiatic acid (AA) on spinal cord injury (SCI)-induced acute lung injury (ALI) have not been investigated. We aimed to investigate the therapeutic efficacy and molecular mechanisms of AA on SCI-induced ALI. One-hundred and fifty Sprague-Dawley rats were randomly assigned to five groups: sham, SCI, SCI + dexamethasone (Dex, 2 mg/kg), SCI + AA (30 mg/kg), and SCI + AA (75 mg/kg). The influences of AA on histologic changes, pulmonary edema, neutrophil infiltration and activation, proinflammatory cytokine production, oxidative stress, and Nrf2 and NLRP3 inflammasome protein expression were estimated. AA administration at the 30- and 75-mg/kg doses significantly attenuates lung wet-to-dry weight (W/D) ratio, pulmonary permeability index (PPI), and pulmonary histologic conditions. Furthermore, the protective effects of AA might be attributed to the reduction of neutrophil infiltration, myeloperoxidase (MPO), inflammatory cytokines, reactive oxygen species (ROS), malondialdehyde (MDA), and the increase of superoxide dismutase (SOD) and catalase (CAT). Moreover, AA markedly upregulated Nrf2 levels and downregulated NLRP3 inflammasome protein expression in lung tissues. AA exhibits a protective effect on SCI-induced ALI by alleviating the inflammatory response, by inhibiting NLRP3 inflammasome activation and oxidative stress with the upregulation of Nrf2 protein levels. The use of AA may be a potential efficient therapeutic strategy for the treatment of SCI-induced ALI.

Keywords: NLRP3 inflammasome; Nrf2; acute lung injury; asiatic acid; spinal cord injury.