Naringin, a flavanone glycoside, promotes angiogenesis and inhibits endothelial apoptosis through modulation of inflammatory and growth factor expression in diabetic foot ulcer in rats

作者：Kandhare Amit D; Ghosh Pinaki; Bodhankar Subhash L^*

来源：Chemico-Biological Interactions, 2014, 219: 101-112.

DOI：10.1016/j.cbi.2014.05.012

• Ang-1
• Collagen-1
• Diabetic foot ulcer
• IFG-1
• Naringin
• VEGF-c

Chronic, unhealed diabetic foot ulcer (DFU) is one of the most severe complications of diabetes mellitus (DM). Naringin, a flavanone glycoside antioxidant, was reported to have antidiabetic and anti-apoptotic properties. In the present study DM was induced experimentally by streptozotocin (STZ, 55 mg/kg, i.p.). In surgically introduced wounds on the dorsal surface of the hind paw of rats, the healing potential of naringin was investigated. Rats were treated with naringin (20, 40 and 80 mg/kg, p.o.), insulin (10 IU/kg, s.c.) and tetrachlorodecaoxide (TCDO) (1 drop, twice a day, topically) for 16 days. The wound area was measured every second day, and on day 17 various biochemical parameters were determined in serum, wound tissue, and histopathological examination of the wound was performed. Naringin (40 and 80 mg/kg) significantly (P < 0.05) improved wound area, serum glucose level, glycated Hb and serum insulin. Naringin treatment at 40 and 80 mg/kg resulted in significant (P < 0.05) up-regulation of mRNA expression of growth factor (IFG-1, TGF-beta and VEGF-c), Ang-1 and collagen-1 whereas mRNA expression of inflammatory mediators (TNF-alpha, IL-1 beta and IL-6) was down-regulated. Furthermore, naringin significantly (P < 0.05) attenuated STZ-induced apoptosis and stimulated angiogenesis in the wound tissue. Further results suggest that angiogenesis was improved via naringin-mediated inhibition of hyper-glycemia, oxidative stress, down-regulation of inflammatory mediator expression and up-regulation of growth factor expression, leading to improved wound healing of DFU.

• 出版日期2014-8-5