Urolithin A ameliorates diabetic retinopathy via activation of the Nrf2/HO-1 pathway

Endocrine journal

article

Zepeng Xu¹  Songtao Li²  Kunmeng Li³  Xiaoyu Wang²  Xiaojie Li²  Meixia An⁴  Xiaoyi Yu³  Xinguang Long¹  Ruiying Zhong³  Qiuhong Liu³  Xiaochuan Wang³  Yan Yang³  Ni Tian³ 

[1] Department of Ophthalmology, Wuyi Hospital of Traditional Chinese Medicine, Guangdong Province;The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangdong Province;Department of Ophthalmology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Province;Department of Ophthalmology, The Third Affiliated Hospital of Southern Medical University, Guangdong Province

关键词: Urolithin A;    Diabetic retinopathy;    Inflammation;    Oxidative stress;    Nrf2/HO-1 pathway;   

DOI  :  10.1507/endocrj.EJ21-0490

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

Diabetic retinopathy (DR) is a progressive microvascular complication of diabetes mellitus and is characterised by excessive inflammation and oxidative stress. Urolithin A (UA), a major metabolite of ellagic acid, exerts anti-inflammatory and antioxidant functions in various human diseases. This study, for the first time, uncovered the role of UA in DR pathogenesis. Streptozotocin-induced diabetic rats were used to determine the effects of UA on blood glucose levels, retinal structures, inflammation, and oxidative stress. High glucose (HG)-induced human retinal endothelial cells (HRECs) were used to elucidate the anti-inflammatory and antioxidant mechanisms of UA in DR in vitro. The in vivo experiments demonstrated that UA injection reduced blood glucose levels, decreased albumin and vascular endothelial growth factor concentrations, and ameliorated the injured retinal structures caused by DR. UA administration also inhibited inflammation and oxidative damage in the retinal tissues of diabetic rats. Similar anti-inflammatory and antioxidant effects of UA were observed in HRECs induced by HG. Furthermore, we found that UA elevated the levels of nuclear Nrf2 and HO-1 both in vivo and in vitro. Nrf2 silencing reversed the inhibitory effects of UA on inflammation and oxidative stress during DR progression. Together, our findings indicate that UA can ameliorate DR by repressing inflammation and oxidative stress via the Nrf2/HO-1 pathway, which suggests that UA could be an effective drug for clinical DR treatment.

【 授权许可】

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