Oridonin supplementation attenuates atherosclerosis via NLRP-3 inflammasome pathway suppression.

ABSTRACT

Atherosclerosis, a long-term inflammatory and immune condition affecting medium- and large-sized arteries, results in the thickening of artery walls and the accumulation of inflammatory cells and fatty streaks that establish fibrous capsules with macrophages at the site of injury. Atherosclerosis has a major impact on the pathogenesis of cardiovascular diseases. Oridonin has been shown to exclusively inhibit the NLRP3 inflammasome without affecting the activation of AIM-2 or NLRC-4 inflammasomes. The current study aimed to evaluate how adding Oridonin to a diet impacts the onset of atherosclerosis. Twenty-one male rabbits weighing 1.5 to 2.0 kg were included in the study. The rabbits were kept in controlled environmental conditions and divided into three groups a normal control group fed a conventional chow diet, an atherogenic control group fed a high-cholesterol diet (2% cholesterol-rich), and an Oridonin-treated group (Ori) fed an atherogenic diet supplemented with Oridonin (20 mg/kg) administered orally once daily. Compared to animals on a normal diet, an atherogenic diet was associated with a statistically significant (p=0.001) increase in the mean expression of the NLRP3 inflammasome mRNA. The Oridonin-treated group showed a statistically significant (p=0.001) decline in the mean expression of NLRP3 inflammasome mRNA compared to the atherogenic group. Furthermore, the initial atherosclerotic lesion in the group treated with Oridonin was statistically (p=0.001) less severe compared to the atherogenic group. Finally, Ori treated group had significantly (p≤0.001) lower IL-1B immunostaining intensity than the atherogenic group (mean rank 14.5,25 respectively). The study concluded that Oridonin supplementation resulted in less severe initial atherosclerotic lesions, likely due to the suppression of NLRP3 inflammasome and the anti-inflammatory effect through the downregulation of IL1B expression.