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

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          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-1 β and TNF- α in the kidney were also evaluated. Alterations in the expression of podocin, CD2AP 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-1 β). 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.

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          Author and article information

          Chinese Journal of Natural Medicines
          20 May 2019
          : 17
          : 5
          : 346-354
          1 College of Pharmacy, Ningxia Medical University, Yinchuan 750004, China
          2 School of Rehabilitation Medicine, Binzhou Medical University, Yantai 264003, China
          3 School of Health Sciences, Macao Polytechnic Institute, Macao SAR 999078, China
          4 Nanjing Dorra Pharmaceutical Co., Ltd., Nanjing 210012, China
          5 Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China
          Author notes
          *Corresponding author: CHENG Xiao-Lan, Tel: 86-25-52362182, Fax: 86-2552362182, E-mail: chengxiaolan37@ 123456126.com ; WANG Qi, E-mail: cpuwangqi@ 123456163.com

          ΔThese authors contributed to the work equally.

          These authors have no conflict of interest to declare.

          Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funded by: National Natural Science Foundation of China
          Award ID: 81503559
          This work was supported by the National Natural Science Foundation of China (No. 81503559).


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