Oleanolic acid alleviates diabetic rat carotid artery injury through the inhibition of NLRP3 inflammasome signaling pathways

Abstract

The overexpression of inflammasome components is correlated with diabetes-associated complications. Oleanolic acid is a triterpenoid compound which is important in arterial injury. The present study evaluated whether oleanolic acid improved diabetic rat carotid artery injury through the inhibition of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasomes signaling pathways. A diabetic rat model was induced using streptozotocin (60 mg/kg) and underwent carotid artery injury. Morphometric analysis was performed using hematoxylin and eosin staining. The mRNA and protein levels were assayed by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. It was found that olea-nolic acid (100 mg/kg/day) improved body weight, glucose metabolic disorders, neointimal hyperplasia and endothelial dysfunction in diabetic rats with carotid artery injury. In addition, oleanolic acid administration significantly downregulated the mRNA and protein expression levels of endothelin 1 in diabetic rats. Oleanolic acid decreased the intimal area and the ratio of neointima to media in diabetic rats. Serum levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-18 in the oleanolic acid-treated diabetic rats were downregulated. Consistent with the serum results, it was demonstrated that oleanolic acid administration caused a significant decrease in the levels of NLRP3, caspase-1 and IL-1β in the carotid arteries of diabetic rats. Taken together, these observations suggested that oleanolic acid attenuated carotid artery injury in diabetic rats and the underlying mechanism was mediated, at least partially, through the suppression of NLRP3 inflam-masome signaling pathways.