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Hesperetin ameliorates diabetic nephropathy in rats by activating Nrf2/ARE/glyoxalase 1 pathway.
Biomed Pharmacother. 2019 Mar; 111:1166-1175.BP

Abstract

Diabetic nephropathy (DN) is one of the most common diabetic complications, and alpha-carbonyl aldehydes and their detoxicating enzyme glyoxalase 1 (Glo-1) play vital roles in pathogenesis of diabetic complications. The aim of this study was to evaluate the renoprotective effects of hesperetin against DN in rats, and to investigate mechanisms from the aspect of Nrf2/ARE/Glo-1 pathway. Streptozotocin-induced diabetic rats were treated orally with hesperetin (50 and 150 mg/kg), or nuclear factor erythroid-derived-2-like 2 (Nrf2) inducer tert-butylhydroquinone (tBHQ, 25 mg/kg) for 10 weeks. Then proteinuria, creatinine, urea nitrogen, and uric acid were assayed for renal functions, fibronectin and collagen IV levels by immunohistochemistry, as well as periodic acid-Schiff staining and electron microscope observation, were used to assess renal morphology. Glo-1 activity, protein, and mRNA levels and the classic Nrf2/ARE pathway were investigated. Moreover, advanced glycation endproducts (AGEs) and its receptor RAGE, interleukin-1β and tumor necrosis factor-α levels were also examined in the kidney. Hesperetin markedly ameliorated the renal functions and structural changes of diabetic rats, accompanied by up-regulation of Glo-1 as well as inhibition of AGEs/RAGE axis and inflammation. Meanwhile, hesperetin caused significant increases in Nrf2 and p-Nrf2 levels, as well as up-regulation of γ-glutamylcysteine synthetase, a well-known target gene of Nrf2/ARE signaling. Our results demonstrated that hesperetin could slow down the pathological process of DN, and Glo-1 enhancement contributed to the beneficial effects, which was obtained by the activation of Nrf2/ARE pathway.

Authors+Show Affiliations

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.College of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology, Suzhou 215009, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China; Department of Pharmacology, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China. Electronic address: ywliu@xzhmu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30841430

Citation

Chen, Ya-Jing, et al. "Hesperetin Ameliorates Diabetic Nephropathy in Rats By Activating Nrf2/ARE/glyoxalase 1 Pathway." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 111, 2019, pp. 1166-1175.
Chen YJ, Kong L, Tang ZZ, et al. Hesperetin ameliorates diabetic nephropathy in rats by activating Nrf2/ARE/glyoxalase 1 pathway. Biomed Pharmacother. 2019;111:1166-1175.
Chen, Y. J., Kong, L., Tang, Z. Z., Zhang, Y. M., Liu, Y., Wang, T. Y., & Liu, Y. W. (2019). Hesperetin ameliorates diabetic nephropathy in rats by activating Nrf2/ARE/glyoxalase 1 pathway. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 111, 1166-1175. https://doi.org/10.1016/j.biopha.2019.01.030
Chen YJ, et al. Hesperetin Ameliorates Diabetic Nephropathy in Rats By Activating Nrf2/ARE/glyoxalase 1 Pathway. Biomed Pharmacother. 2019;111:1166-1175. PubMed PMID: 30841430.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hesperetin ameliorates diabetic nephropathy in rats by activating Nrf2/ARE/glyoxalase 1 pathway. AU - Chen,Ya-Jing, AU - Kong,Li, AU - Tang,Zhuang-Zhuang, AU - Zhang,Yu-Meng, AU - Liu,Yue, AU - Wang,Tao-Yun, AU - Liu,Yao-Wu, Y1 - 2019/01/12/ PY - 2018/11/23/received PY - 2019/01/07/revised PY - 2019/01/08/accepted PY - 2019/3/8/entrez PY - 2019/3/8/pubmed PY - 2019/6/22/medline KW - AGEs/RAGE axis KW - Diabetic nephropathy KW - Glyoxalase 1 KW - Hesperetin KW - Nrf2/ARE pathway SP - 1166 EP - 1175 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 111 N2 - Diabetic nephropathy (DN) is one of the most common diabetic complications, and alpha-carbonyl aldehydes and their detoxicating enzyme glyoxalase 1 (Glo-1) play vital roles in pathogenesis of diabetic complications. The aim of this study was to evaluate the renoprotective effects of hesperetin against DN in rats, and to investigate mechanisms from the aspect of Nrf2/ARE/Glo-1 pathway. Streptozotocin-induced diabetic rats were treated orally with hesperetin (50 and 150 mg/kg), or nuclear factor erythroid-derived-2-like 2 (Nrf2) inducer tert-butylhydroquinone (tBHQ, 25 mg/kg) for 10 weeks. Then proteinuria, creatinine, urea nitrogen, and uric acid were assayed for renal functions, fibronectin and collagen IV levels by immunohistochemistry, as well as periodic acid-Schiff staining and electron microscope observation, were used to assess renal morphology. Glo-1 activity, protein, and mRNA levels and the classic Nrf2/ARE pathway were investigated. Moreover, advanced glycation endproducts (AGEs) and its receptor RAGE, interleukin-1β and tumor necrosis factor-α levels were also examined in the kidney. Hesperetin markedly ameliorated the renal functions and structural changes of diabetic rats, accompanied by up-regulation of Glo-1 as well as inhibition of AGEs/RAGE axis and inflammation. Meanwhile, hesperetin caused significant increases in Nrf2 and p-Nrf2 levels, as well as up-regulation of γ-glutamylcysteine synthetase, a well-known target gene of Nrf2/ARE signaling. Our results demonstrated that hesperetin could slow down the pathological process of DN, and Glo-1 enhancement contributed to the beneficial effects, which was obtained by the activation of Nrf2/ARE pathway. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/30841430/Hesperetin_ameliorates_diabetic_nephropathy_in_rats_by_activating_Nrf2/ARE/glyoxalase_1_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(18)38242-8 DB - PRIME DP - Unbound Medicine ER -