Involvement of SIRT1-eNOS Axis in Vascular Senescence Responses to Ursolic Acid and Exercise Training in Aged Type 2 Diabetes Model of Rats

Abstract Background Ursolic acid (UA) mediates the vasorelaxant activity via nitric oxide (NO) release, and up-regulation of eNOS in endothelial cells in disease conditions with increased oxidative stress. The present study aimed to reflect on the impact of eight weeks of a combination of ursolic acid (UA) supplementation and resistance/endurance training in old male Wistar rats having high-fat diet and/or low-dose streptozotocin-induced type 2 diabetes (HFD/STZ-induced T2D), with an emphasis on sirtuin 1 (SIRT1)-endothelial nitric oxide synthase (eNOS) axis and oxidative stress (OS) indices in their aortic tissues. Methods A total number of 56 21-month-old male Wistar rats with HFD/STZ-induced T2Dwere randomized into seven groups (n = eight animals per group): (1) sedentary old non-diabetic (C); (2) sedentary HFD/STZ-induced T2D (D); (3) sedentary HFD/STZ-induced T2D plus UA (UA) (DU); (4) endurance-trained HFD/STZ-induced T2D (DE); (5) resistance-trained HFD/STZ-induced T2D (DR); (6) endurance-trained HFD/STZ-induced T2D plus UA (DEU); and (7) resistance-trained STZ-diabetic plus UA (DRU) rats. Results The study results established no significant interaction between the UA supplementation and the resistance/endurance training with regard to the levels of glucose (p = 0.534), insulin (p = 0.327), high-density lipoprotein cholesterol (HDL-c) (p = 0.960), cholesterol (p = 0.107), SIRT1 (p = 0.640), and eNOS (p = 0.151). However, the resistance/endurance training plus the UA consumption could partially reverse the levels of malondialdehyde (MDA) (p = 0.001), nitric oxide (NO) (p = 0.009), as well as total antioxidant capacity (TAC) (p = 0.016). Conclusions In general, the UA supplementation combined with the resistance/endurance training did not affect vascular aging biomarkers. To develop novel practical nutritional strategies involving UA intake, further studies are thus needed to clarify how chronic consumption of UA with/without resistance/endurance training reverses vascular aging process in old male Wistar rats with HFD/STZ-induced T2D.