Long-Term In Vivo Administration of Panaxynol Alleviates Diabetes-Induced Vascular Calcification by Modulating Sirt6-Mediated sEH Function in Perivascular Adipose Tissue

Panaxynol (PA), a bioactive compound found in carrots and other Apiaceae plants, holds promise for managing diabetes-related vascular complications. This study investigated the long-term effects of PA on diabetes-induced vascular calcification (DVC) in db/db mice for up to 9 weeks. The impact of PA on DVC was evaluated both in vivo and in vitro using immunohistochemical staining, Western blotting, micro-computed tomography, and other analytical techniques. Results demonstrated that PA significantly attenuated arterial calcification and collagen hyperplasia in the aorta. Additionally, PA elevated levels of the lipid signaling molecule 14,15-EET, which preserved the vascular structure and function by reducing inflammatory macrophage infiltration in perivascular adipose tissue. This protective effect was partially attributed to the PA-mediated inhibition of soluble epoxide hydrolase (sEH) through Sirt6 activation. These findings highlight PA as a potential natural therapeutic strategy for mitigating diabetic vascular complications and offer an alternative to conventional pharmacological approaches.