Crocetin restores diabetic endothelial progenitor cell dysfunction by enhancing NO bioavailability via regulation of PI3K/AKT-eNOS and ROS pathways

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Endothelial progenitor cell (EPC) dysfunction underlies a critical risk factor in diabetic vascular complications due to function defect in restoring endothelium injury. Crocetin has attracted increasing attention in several vascular-related diseases. In present study, we aimed to explore the role of crocetin in diabetic EPC dysfunction.

Main methods:

EPCs were isolated from bone marrow in diabetic mice and identified using the fluorescence staining and flow cytometry. After exposure to various doses of crocetin, cell viability was detected by MTT assy. Then, colony formation, lactate dehydrogenase (LDH) release, cell apoptosis and caspase-3 activity were assessed. The underlying mechanism was also investigated by western blotting.

Key findings:

EPCs from diabetic mice exhibited dysfunction under hyperglycemia condition. Interestingly, crocetin treatment alleviated the impairment in diabetic EPC proliferation and colony formation. Simultaneously, the increases in LDH release, cell apoptosis and caspase-3 activity were also restrained following crocetin stimulation. Additionally, EPC migration response to SDF-1 was also impaired under diabetic condition, which was partly restored by crocetin. Mechanism analysis manifested that administration with crocetin repaired the damage in the activation of PI3K/AKT-eNOS pathway and NO production, but attenuated ROS elevation in diabetic EPCs. Importantly, preconditioning with antagonist of LY294002 (for PI3K/AKT) or NG-monomethyl-l-arginine (for eNOS) antagonized the beneficial effect of crocetin on diabetic EPC dysfunction.


These data corroborated that crocetin could restore the dysfunction of diabetic EPCs by enhancing NO bioavailability via regulation of PI3K/AKT-eNOS and ROS pathways. Therefore, this research supports a potential promising therapeutic aspect for diabetic patients.

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