Research Paper Volume 10, Issue 12 pp 4197—4212
Hyperoside attenuates renal aging and injury induced by D-galactose via inhibiting AMPK-ULK1 signaling-mediated autophagy
- 1 Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, China
- 2 Department of Nephrology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- 3 Department of TCM Health Preservation, Second Clinic Medical School, Nanjing University of Chinese Medicine, Nanjing 210023, China
- 4 Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
- 5 Institute of Huangkui, Suzhong Pharmaceutical Group Co., Ltd., Taizhou 225500, China
- 6 Department of Social Work, Meiji Gakuin University, Tokyo 108-8636, Japan
Received: June 28, 2018 Accepted: December 12, 2018 Published: December 24, 2018
https://doi.org/10.18632/aging.101723How to Cite
Copyright: Liu et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The kidney is a typical organ undergoing age and injury. Hyperoside is reported to be useful for preventing aging induced by D-galactose (D-gal). However, therapeutic mechanisms remain unclear. We thereby aimed to verify whether hyperoside, compared to vitamin E (VE), could alleviate renal aging and injury by regulating autophagic activity and its related signaling pathways. In vivo, rats were administered with either hyperoside or VE after renal aging modeling induced by D-gal. Changes in renal aging and injury markers, autophagic activity and AMPK-ULK1 signaling pathway in the kidneys were analysed. In vitro, the NRK-52E cells exposed to D-gal were used to investigate regulative actions of hyperoside and VE on cell viability, renal tubular cellular aging markers, autophagic activity and its related signaling pathways by histomorphometry, immunohistochemistry, immunofluorescence, lentiviral transfection and Western blot. Aging and injury in the kidneys and renal tubular cells induced by D-gal were ameliorated by hyperoside and VE. Hyperoside and VE inhibited autophagic activity through mTOR-independent and AMPK-ULK1 signaling pathways. Hyperoside, as a component of phytomedicine similar to VE, attenuated renal aging and injury induced by D-gal via inhibiting AMPK-ULK1-mediated autophagy. This study provides the first evidence that hyperoside contributes to the prevention of age-associated renal injury.
Abbreviations
4EBP1: eukaryotic initiation factor 4E-binding protein-1; Akt: serine-threonine kinase; AM: abelmoschus manihot; AMPK: adenosine monophosphate-activated protein kinase; Atg: autophagy related gene; BUN: blood urea nitrogen; CC: compound C; CKD: chronic kidney disease; CR: calorie restriction; D-gal: D-galactose (D-gal); FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HRP: horseradish peroxidase; IL-1: interleukin-1; MCP-1: monocyte chemoattractant protein-1; MOI: multiplicity of infection; mTOR: mammalian target of rapamycin; OD: optical density; p70S6K: 70-kDa ribosomal protein S6; p-AMPK: phosphorylation of AMPK; PBS: phosphate buffered saline; PI3K: phosphatidylinositol-3-kinase; PTCs: proximal tubular cells; p-ULK1: phosphorylation of ULK1; SA-β-gal: senescence-associated-β-galactosidase staining; Scr: serum creatinine; SD: Sprague-Dawley; sirtuin 1: oxidized nicotinamide adenine dinucleotide-dependent histone deacetylase; TCM: traditional Chinese medicine; TGF-β: transforming growth factor-β; ULK1: unc-51 like autophagy activating kinase 1; VE: vitamin E; WB: Western blot.