Protective effect of ginsenoside Rb1 against intestinal ischemia-reperfusion induced acute renal injury in mice

PLoS One. 2013 Dec 4;8(12):e80859. doi: 10.1371/journal.pone.0080859. eCollection 2013.

Abstract

Ginsenoside Rb1 (RB1), the most clinically effective constituent of ginseng, possesses a variety of biological activities. The objectives of this study were to investigate the protective effects of RB1 and its underlying mechanism on renal injury induced by intestinal ischemia-reperfusion (IIR) in mice. RB1 was administered prior to inducing IIR achieved by occluding the superior mesenteric artery for 45 min followed by 120 min of reperfusion. All-trans-retinoic acid (ATRA) was used as an inhibitor of NF-E2-related factor-2 (Nrf2) signaling. Adult male C57BL/6J mice were randomly divided into six groups: (1) sham group, (2) IIR group, (3) RB1 group, (4) sham + ATRA group, (5) IIR + ATRA group, and (6) RB1 + ATRA group. Intestinal histology and pathological injury score were observed. Intestinal mucosal injury was also evaluated by measuring serum diamine oxidase (DAO). Renal injury induced by IIR was characterized by increased levels of histological severity score, blood urea nitrogen (BUN), serum creatinine (Scr) and neutrophil gelatinase-associated lipocalin (NGAL), which was accompanied with elevated renal TUNEL-positive cells and the Bcl-2/Bax expression ratio. RB1 significantly reduced renal injury and apoptosis as compared with IIR group, which was reversed by ATRA treatment. Immunohistochemistry and Western blot analysis demonstrated that RB1 significantly upregulated the protein expression of heme oxygenase-1 (HO-1) and Nrf2, which were attenuated by ATRA treatment. Taken together, these results suggest that the protective effects of RB1 pretreatment against renal injury induced by IIR are associated with activation of the Nrf2/ anti-oxidant response element (ARE) pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control*
  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism
  • Amine Oxidase (Copper-Containing) / blood
  • Animals
  • Antioxidants / pharmacology*
  • Blood Urea Nitrogen
  • Creatinine / blood
  • Gene Expression Regulation
  • Ginsenosides / pharmacology*
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects
  • Intestines / pathology
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Lipocalin-2
  • Lipocalins / genetics
  • Lipocalins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / agonists
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Oxidative Stress / drug effects
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Signal Transduction
  • Tretinoin / pharmacology
  • bcl-2 Homologous Antagonist-Killer Protein / genetics
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Acute-Phase Proteins
  • Antioxidants
  • Ginsenosides
  • Lipocalin-2
  • Lipocalins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Oncogene Proteins
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • Lcn2 protein, mouse
  • Tretinoin
  • ginsenoside Rb1
  • Creatinine
  • Amine Oxidase (Copper-Containing)

Grant support

This work was supported by the National Natural Science Foundation of China (No. 81000027). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.