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 (S1RT1), 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-a), and oxidative stress markers (catalase, superoxide dismutase and malonaldehyde). In addition, both treatments significantly upregulated the gene expression of S1RT1, 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.
Conflict of interest statement
The authors declare that there is no conflict of interest.
Funding
This article is funded by HEC, 520-163233-2AV6-09, Anam Iqbal.
Data availability statement
The data supporting the findings of this study are available from the corresponding author upon request.
Authors’ contributions
MHM developed the concept of study and layout of the project. He supervised this project completely and has also been involved in data acquirement and analysis, writing, reviewing and submission of the manuscript. AI was involved in concept design, performance of experiments, data collection, analysis and manuscript writing. SM and RS were involved in data collection, analysis, manuscript writing and reviewing. MNF was involved in quantitative analysis of candidate genes of diabetes studied in this manuscript and reviewing of the manuscript.
Publisher’s note
The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Acknowledgments
We would like to acknowledge Higher Education Commission of Pakistan for providing HEC Indigenous PhD fellowship (Phase-II) to carry out PhD studies with PIN No.: 520-163233-2AV6-09.
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