Ursolic acid (UA) mediates the vasorelaxant activity via nitric oxide (NO) release, and upregulation of endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs) in disease conditions with increased oxidative stress (OS). The present study aimed to reflect on the impact of 8 weeks of a combination of UA supplementation and resistance/endurance training in old male Wistar rats having a 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 OS indices in their aortic tissues. A total number of56 21‐month‐old male Wistar rats with HFD/STZ‐induced T2D were randomized into seven groups (n = eight animals per group): (1) sedentary old nondiabetic (Control [C]); (2) sedentary HFD/STZ‐induced T2D (Diabetic [D]); (3) sedentary HFD/STZ‐induced T2D plus UA (Diabetic + Ursolic Acid [DU]); (4) endurance‐trained HFD/STZ‐induced T2D (Diabetic + Endurance Training [DE]); (5) resistance‐trained HFD/STZ‐induced T2D (Diabetic + Resistance Training [DR]); (6) endurance‐trained HFD/STZ‐induced T2D plus UA (Diabetic + Endurance Training + Ursolic Acid [DEU]); and (7) resistance‐trained STZ–diabetic plus UA (Diabetic + Resistance Training + Ursolic Acid [DRU]) rats. The ladder‐based resistance training group performed the ladder resistance training at 60% of the maximum voluntary carrying capacity (MVCC), 14–20 climbs in each session, with a one‐min rest between each two trials, 5 days a week. The treadmill‐based endurance exercise training protocol consisted of repeated bouts of high‐ and low‐intensity training with 60–75% maximal running speed and 30%–40% maximal running speed in the course of 8 weeks, respectively. The animals in the supplement groups also took 500 mg of UA/kg of high‐fat diet/day, resulting in a daily UA intake of approximately 250 mg UA per kg of body weight rat/day. The resistance/endurance training plus the UA consumption could partially reverse the levels of malondialdehyde (MDA), nitric oxide (NO), as well as total antioxidant capacity (TAC). It was concluded that oral 0.5% UA supplementation can prevent vascular aging biomarkers in a HFD/STZ‐induced T2D model. Further studies are also required to clarify how chronic consumption of UA with/without training protocols reverses vascular aging process.

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.