Umbelliferone ameliorates renal function in diabetic nephropathy rats through regulating inflammation and TLR/NF-κB pathway  

作　　者：WANG Han-Qing WANG Sha-Sha Chiufai Kuok WANG Qi CHENG Xiao-Lan 

机构地区：[1]College of Pharmacy, Ningxia Medical University [2]School of Rehabilitation Medicine, Binzhou Medical University [3]School of Health Sciences, Macao Polytechnic Institute [4]Nanjing Dorra Pharmaceutical Co., Ltd. [5]Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine

出　　处：《Chinese Journal of Natural Medicines》2019年第5期346-354,共9页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.81503559)

摘　　要：Diabetic nephropathy(DN) is a leading cause of renal failure, contributing to severe morbidity and mortality in diabetic patients. Umbelliferae(Umb) has been well characterized to exert protective effects in diabetes. However, the action and mechanism of Umb in DN remains unclear. In this work, we studied the effect of Umb in a streptozotocin(STZ)-induced DN rat model and explore its underlying mechanism. DN rats were treated with Umb(20, 40 mg·kg^(-1)) or irbesartan(15 mg·kg^(-1)) for 4 weeks. Levels of serum glucose, insulin, blood uric acid, creatinine, triglycerides(TG) and total cholesterol(TC) were measured by commercial assay kits,respectively. Histopathological changes and inflammatory cytokine levels including IL-6, IL-1β and TNF-α in the kidney were also evaluated. Alterations in the expression of podocin, CD2 AP and TLR/NF-κB were assessed by western blotting. Our results showed that Umb reduced renal injury in DN rat model, as evidenced by the decrease in blood glucose, 24 h urinary protein, serum creatinine,and blood uric acid. Umb also significantly ameliorated the renal histopathological alteration, and down-regulated the expression of epithelial-to-mesenchymal transition-related molecular markers podocin and CD2AP. Moreover, Umb inhibited TLR2, TLR4, MyD88 expressions, NF-κB activation and considerably reduced levels of other downstream inflammatory molecules(TNF-α, IL-6, IL-1β).These findings indicated that Umb improved renal function through regulating inflammation and TLR/NF-κB pathway, suggesting the potential efficacy of Umb in DN treatment.Diabetic nephropathy(DN) is a leading cause of renal failure, contributing to severe morbidity and mortality in diabetic patients. Umbelliferae(Umb) has been well characterized to exert protective effects in diabetes. However, the action and mechanism of Umb in DN remains unclear. In this work, we studied the effect of Umb in a streptozotocin(STZ)-induced DN rat model and explore its underlying mechanism. DN rats were treated with Umb(20, 40 mg·kg^(-1)) or irbesartan(15 mg·kg^(-1)) for 4 weeks. Levels of serum glucose, insulin, blood uric acid, creatinine, triglycerides(TG) and total cholesterol(TC) were measured by commercial assay kits,respectively. Histopathological changes and inflammatory cytokine levels including IL-6, IL-1β and TNF-α in the kidney were also evaluated. Alterations in the expression of podocin, CD2 AP and TLR/NF-κB were assessed by western blotting. Our results showed that Umb reduced renal injury in DN rat model, as evidenced by the decrease in blood glucose, 24 h urinary protein, serum creatinine,and blood uric acid. Umb also significantly ameliorated the renal histopathological alteration, and down-regulated the expression of epithelial-to-mesenchymal transition-related molecular markers podocin and CD2AP. Moreover, Umb inhibited TLR2, TLR4, MyD88 expressions, NF-κB activation and considerably reduced levels of other downstream inflammatory molecules(TNF-α, IL-6, IL-1β).These findings indicated that Umb improved renal function through regulating inflammation and TLR/NF-κB pathway, suggesting the potential efficacy of Umb in DN treatment.

关 键 词：Diabetic nephropathy UMBELLIFERONE STREPTOZOTOCIN INFLAMMATION TLR/NF-κB pathway 

分 类 号：R965[医药卫生—药理学]