Chrysophanol exerts protective effect against atherosclerosis via NFκB-mediated signaling in LDLR-/- mice model

Abstract

Purpose: To study the therapeutic effect of chrysophanol (CHR) on diet-induced atherogenesis in LDLR-/- mice.Methods: Mice were fed atherogenic diet for 12 weeks after which some lipid profile markers such as total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and triglyceride (TG) were measured. The mRNA expression levels of lipid synthesis genes and lipid overload-related inflammatory indicator molecules were assayed with quantitative real time polymerase chain reaction (qRT-PCR), while the corresponding protein expressions were determined with western blotting assay. The therapeutic effect of CHR on atherogenesis was confirmed using H & E and Oil red O stainings of mice aortic sections.Results: CHR administration significantly reduced levels of TC, LDL-c, HDL-c and TG (p ≤ 0.05), and restored the mRNA and protein expressions of genes involved in lipid and glucose homeostasis, namely, AdipoR1, PPAR-Ƴ and HMco-A (p < 0.05). Moreover, CHR potentially alleviated diet-induced inflammation, as is evident in reduced levels of molecular inflammatory signaling factors NF-κB and TLR-4, and significant down-regulations of the proinflammatory cytokines, TNF-α, IL-6 and IL-1β (p < 0.05). Furthermore, aorta histology revealed that CHR significantly reduced lipid storage in the arteries of mice fed atherogenic diet (p < 0.05).Conclusion: These results indicate that CHR reduces diet-induced lipid storage in LDLR-/- mice and also controlled inflammation-associated lipid overload. These findings may provide a molecular basis for potential application of chrysophanol in the treatment of atherosclerosis.