Crocin mitigates atherosclerotic progression in LDLR knockout mice by hepatic oxidative stress and inflammatory reaction reduction, and intestinal barrier improvement and gut microbiota modulation

Crocin has a protective effect on neurodegenerative disease, but whether crocin can prevent atherosclerosis remains unclear. The present study aimed to explore the possible anti-atherosclerotic mechanism of crocin in LDLR-/- mice. Mice were fed an atherogenic high-fat/cholesterol diet and concomitantly treated by intragastric administration with normal saline (Model) or 20 or 40 mg/(kg.bw.day) crocin for 8 weeks. Pathological results showed that Model group exhibited a marked atherosclerotic plaque, while crocin significantly reduced atherosclerotic plaque, accompanied by a small amount of denatured collagen fiber and foam cells. Mechanistically, crocin, especially high-dose suppressed the formation of atherosclerotic plaques via enhancing hepatic antioxidant capacity. Besides, crocin effectively inhibited NLRP3 inflammasome and blocked TLR4 signal, through reducing oxidative stress based on Nrf2/Keap1 pathway, and increasing intestinal tight junction proteins and improving gut microbiota composition. These results suggest that crocin can ameliorate inflammation and attenuate atherosclerotic progression by oxidative stress reduction and intestinal barrier improvement.