Kumquat Flavonoids Attenuate Atherosclerosis in ApoE–/– Mice by Inhibiting the Activation of NLRP3 Inflammasome through Upregulating MicroRNA-145

Atherosclerosis (AS) is widely recognized as a consequence of chronic inflammation, with the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome playing a pivotal role in mediating this inflammatory response. Kumquat flavonoids (KFs), the primary active ingredients in kumquat, have demonstrated potential in modulating inflammation and may help prevent AS. Herein, this study aimed to explore the protective effects and underlying mechanisms of KFs on AS using an ApoE^–/– mouse model fed a high-fat/cholesterol diet (HFCD) and the mouse aortic vascular smooth muscle cell (MOVAS) inflammation model induced by oxidized low-density lipoprotein (ox-LDL). Our results show that KFs significantly reduced serum lipid levels and suppressed the overproduction of inflammatory cytokines in ApoE^–/– mice. Notably, KFs also decreased the area of atherosclerotic lesions and plaque formation in the aorta of ApoE^–/– mice. Additionally, in vivo (mouse aortic tissue) and in vitro (MOVAS cells), KFs were found to inhibit the activation of NLRP3 inflammasome and simultaneously upregulate microRNA-145 (miR-145). In conclusion, our findings suggest that KFs exert their inhibitory effects on NLRP3 inflammasome through upregulating miR-145, thereby alleviating the progression of AS.