1. Academic Validation
  2. Polyacetylene glycoside attenuates ischemic kidney injury by co-inhibiting inflammation, mitochondria dysfunction and lipotoxicity

Polyacetylene glycoside attenuates ischemic kidney injury by co-inhibiting inflammation, mitochondria dysfunction and lipotoxicity

  • Life Sci. 2018 Jul 1;204:55-64. doi: 10.1016/j.lfs.2018.05.009.
Yijie Zhou 1 Dan Du 2 Shuyun Liu 1 Meng Zhao 1 Yujia Yuan 1 Lan Li 1 Younan Chen 1 Yanrong Lu 1 Jingqiu Cheng 3 Jingping Liu 4
Affiliations

Affiliations

  • 1 Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
  • 2 West China-Washington Mitochondria and Metabolism Center, West China Hospital, Sichuan University, Chengdu, China.
  • 3 Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. Electronic address: jqcheng@scu.edu.cn.
  • 4 Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. Electronic address: liujingping@scu.edu.cn.
Abstract

Aims: Ischemic acute kidney injury (AKI) is a serious clinical problem and no efficient therapeutics is available in clinic now. Natural polyacetylene glycosides (PGAs) had shown antioxidant and anti-inflammatory properties, but their effects on kidney injury have not been evaluated. This study aimed to investigate the protective effect of PGA on ischemic kidney injury in renal tubular epithelial cells (TECs) and mice.

Main methods: Hypoxic HK-2 cells and renal ischemia/reperfusion injury (IRI) mice were treated with PGA from Coreopsis tinctoria, and the cell viability, renal function, Apoptosis, inflammation, mitochondrial injury, lipids metabolism were analyzed.

Key findings: In vitro results showed that PGA improved cell viability and reduced oxidative stress, pro-apoptotic/pro-inflammatory factors expression and NFκB activation in TECs under hypoxia/reperfusion (H/R). Moreover, PGA reduced mitochondria oxidative stress and improved ATP production, ΔΨm and mitochondria biogenesis, and inhibited lipids uptake, biosynthesis and accumulation in hypoxic TECs. In vivo, PGA significantly attenuated kidney injury and reduced blood urea nitrogen (BUN), serum creatinine (CREA) and urinary albumin (Alb), and increased creatinine clearance (CC) in IRI mice. PGA also decreased cell Apoptosis, mitochondria oxidative stress, inflammatory response and lipid droplets accumulation, and promoted ATP generation in kidney of IRI mice.

Significance: Our results proved that PGA ameliorated ischemic kidney injury via synergic anti-inflammation, mitochondria protection and anti-lipotoxicity actions, and it might be a promising multi-target therapy for ischemic AKI.

Keywords

Acute kidney injury; Inflammation; Lipotoxicity; Mitochondria; Polyacetylenes glycoside.

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