Rosmarinic acid inhibits nicotine‐induced C‐reactive protein generation by inhibiting NLRP3 inflammasome activation in smooth muscle cells

Abstract

Atherosclerosis is widely known to be a chronic inflammatory disease. C-reactive protein (CRP), an important inflammatory factor, plays an essential role in the pathogenesis of atherosclerosis. Nicotine, the main addictive component of cigarette, has been shown to induce the production of CRP. The aim of this study was to investigate the effect of rosmarinic acid (RA), a polyphenol with antiinflammatory activity, on nicotine-induced elevation of CRP in vascular smooth muscle cells (VSMCs). We found that pretreatment of VSMCs with RA attenuated nicotine-induced expression of CRP in a time- and dose-dependant manner. In addition, RA also inhibited the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and reactive oxygen species (ROS) production resulting from nicotine treatment in VSMCs. To confirm these findings in vivo, we constructed a nicotine-induced atherosclerosis rat model. RA did not significantly reduce the serum nicotine level of the rats, whereas it significantly decreased the levels of serum lipids, including concentrations of cholesterol, triglycerides, and low-density lipoprotein cholesterol, and the serum level of CRP. RA also led to diminished nicotine-induced activation of NLRP3 inflammasome and elevation in the CRP level in the aortic tissue of the model rats. The results of this study suggested a protective role of RA in nicotine-induced atherosclerosis by inhibiting the ROS-NLRP3 inflammasome-CRP axial, and RA therefore represented a potential effective therapeutic approach to atherosclerosis, in particular for those who smoke.

Implication of dietary phenolic acids on inflammation in cardiovascular disease

“…Besides this, it also attenuates cardiac fibrosis in long-term pressure overload via AMPKα/Smad3 Signalling (Zhang et al, 2018). Yao et al (2019) reported that rosmarinic acid inhibits NLRP3 inflammasome activation, resulting in reduced CRP generation in vascular smooth muscle cells. Rosmarinic acid also alleviated cardiomyocyte apoptosis by inhibiting the expression and release of Fas L in cardiomyoblast via the paracrine manner as shown across in vitro assessment.…”

Fucoxanthin and Rosmarinic Acid Combination Has Anti-Inflammatory Effects through Regulation of NLRP3 Inflammasome in UVB-Exposed HaCaT Keratinocytes

“…RA has been widely studied due to its remarkable biological and pharmacological activities, including anti-microbial, antioxidant and anti-inflammatory properties [20]. Until now, only a limited number of studies have dealt with the effect of RA on NLRP3-inflammasome [21,22,23], and none of them on human immortalized HaCaT keratinocytes.…”

CRP-Induced NLRP3 Inflammasome Activation Increases LDL Transcytosis Across Endothelial Cells

“…Meta-analysis of genome-wide association studies has identified NLRP3 as a predictor of CRP levels (Dehghan et al, 2011). A recent study revealed that rosmarinic acid inhibits nicotine-induced AS by suppressing the ROS-NLRP3 inflammasome-CRP axial (Yao et al, 2018). These reports suggest a link between increased levels of CRP and the NLRP3 inflammasome, and thus, a link to AS.…”