摘要Objective:To evaluate the therapeutic potential of coumarin-loaded chitosan nanoparticles(CNNPs)in managing high-fructose diet-induced diabetes and associated complications.Methods:CNNPs were synthesized using an ionic gelation method with chitosan coating and characterized.Rats with a high-fructose diet-induced diabetes were treated with coumarin and CNNPs(30,70,and 100 mg/kg)for 6-12 weeks.Metabolic,inflammatory,oxidative stress,organ function,and cardiovascular parameters were assessed,and qRT-PCR studies were carried out for measuring the mRNA expression of glucose transporter-4(GLUT-4),sirtuin-1(SIRT1),pyrin domain containing-3(NLRP3),sterol regulatory element binding protein 1c(SREBP-1c),forkhead box O3(FOXO3),and endothelial nitric oxide synthase(eNOS)genes.Results:Nanoparticle characterization revealed a Z-average size of 510.8 nm with a+14 mV zeta potential.CNNP treatment was more effective than coumarin,normalizing glycemic markers(glycosylated hemoglobin,serum insulin,and fasting blood glucose),and lipid profiles(total cholesterol,low-density lipoprotein cholesterol,triglycerides,and high-density lipoprotein cholesterol).Significant improvements were also seen in adipokines(adiponectin,chemerin,and leptin),inflammatory cytokines(interleukin-6 and tumor necrosis factor-α),and oxidative stress markers(catalase,superoxide dismutase and malonaldehyde).In addition,both treatments significantly upregulated the gene expression of SIRT1,GLUT-4,and eNOS,and downregulated FOXO3,SREBP-1c,and NLRP3.Histopathological studies confirmed that CNNPs ameliorated diabetes-induced structural abnormalities in major organs.Conclusions:CNNPs demonstrate improved bioavailability and therapeutic efficacy,offering a promising strategy for managing high-fructose diet-induced metabolic dysfunction and its complications.