Crocin and voluntary exercise promote heart angiogenesis through Akt and ERK1/2 signalling in type 2 diabetic rats

signalling. Animals were divided into 4 groups as follows: diabetes (Dia), diabetic-crocin (Dia-Cro), diabetic-voluntary exercise (Dia-Exe), diabetic-crocin-voluntary exercise (Dia-Cro-Exe). Type 2 diabetes was induced by high-fat diet (4 weeks) and injection of streptozotocin (STZ) (i.p., 35 mg/kg). Animals received crocin orally (50 mg/kg), voluntary exercise was performed alone or together with crocin for 8 weeks. Akt and ERK1/2 levels were measured by ELISA and CD31 was detected by immunohistochemistry. Akt and ERK1/2 levels in crocin and exercise groups were significantly higher than in diabetic group. Levels of Akt and ERK1/2 proteins and CD31 immunostaining were also significantly higher in crocin-voluntary exercise group in comparison to the other groups. Our results revealed that treatments with crocin and voluntary exercise had synergistic effect on angiogenesis. Protective effects of these interventions are probably through the activation of Akt and ERK 1/2 signalling pathways in the heart of diabetic rats (Fig. 3, Ref. 40).