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 oleanolic 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 inflammasome signaling pathways.

Olive Leaf Extract (OleaVita) Suppresses Inflammatory Cytokine Production and NLRP3 Inflammasomes in Human Placenta

“…Importantly, we demonstrated that in human placental tissues, OleaVita notably inhibited the activation of NLRP3 inflammasomes, resulting in a decrease in the secretion of mature IL-1β. Consistent with our present results, An et al [31] and Kim et al [19] reported that oleanolic acid attenuated carotid artery and pulmonary injuries through the inhibition of NLRP3 inflammasomes using in vivo experimental models. Recently, NLRP3 inflammasome activation has been shown to be involved in various pregnancy complications, such as preeclampsia, spontaneous preterm labor, and hypertension in pregnancy [9,14].…”

Potential Protective Effect of Oleanolic Acid on the Components of Metabolic Syndrome: A Systematic Review

“…Nonetheless, according to the literature, OA improves beta-cell function through increasing insulin biosynthesis and secretion and also improves glucose tolerance [10]. This idea coincides with different studies included in our review that reported improvements of glucose tolerance both in glucose [35,36,38,39,40,42,46] and in insulin [35,42] tolerance tests, as well as reductions of FBG [30,35,38,42,43,44].…”

“…Another possible hypotensive mechanism of action of OA could be the increase of the production of nitric oxide (NO), a vasodilator factor that is diminished in endothelial disfunction induced by cardiovascular risk factors such as hypertension, obesity, diabetes, and dyslipidemia [15]. This is in agreement with the increase of serum NO levels produced by the action of OA reported by Bachhav et al [28], Jiang et al [32], and An et al [44]. However, Wang et al [43] reported the opposite, which might be explained by the fact that they studied rats [43] fed with a high fat and fructose diet.…”

“…OA administration by An et al [44] to diabetic rats with a carotid artery injury showed a significant reduction of levels of FBG and a significant increase of serum NO level in comparison to non-OA-treated diabetic rats with the same injury.…”

“…In the studies conducted by Pan et al [34], Wang et al [35] and An et al [44], the administration of OA led to significant decreases in serum levels of IL-1β, IL-6, and TNFα. Similarly, a reduction of plasma levels of IL-6 and TNFα was observed by Gamede et al [30].…”