Arginyl-fructosyl-glucose, a Major Maillard Reaction Product of Red Ginseng, Attenuates Cisplatin-Induced Acute Kidney Injury by Regulating Nuclear Factor κB and Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathways

J Agric Food Chem. 2019 May 22;67(20):5754-5763. doi: 10.1021/acs.jafc.9b00540. Epub 2019 May 10.

Abstract

Recently, although ginseng ( Panax ginseng C. A. Meyer) and its main component saponins (ginsenosides) have been reported to exert protective effects on cisplatin (CDDP)-induced acute kidney injury (AKI), the beneficial activities of non-saponin on CDDP-induced AKI is little known. This research was designed to explore the protective effect and underlying mechanism of arginyl-fructosyl-glucose (AFG), a major and representative non-saponin component generated during the process of red ginseng, on CDDP-caused AKI. AFG at doses of 40 and 80 mg/kg remarkably reversed CDDP-induced renal dysfunction, accompanied by the decreased levels of serum creatinine and blood urea nitrogen. Interestingly, all of oxidative stress indices were ameliorated after pretreatment with AFG continuously for 10 days. Importantly, AFG relieved CDDP-induced inflammation and apoptosis in part by mitigating the cascade initiation steps of nuclear factor κB signals and regulating the participation of the phosphatidylinositol 3-kinase/protein kinase B signal pathway. In conclusion, these results clearly provide strong rationale for the development of AFG to prevent CDDP-induced AKI.

Keywords: NF-κB; PI3K/Akt; acute kidney injury; arginyl-fructosyl-glucose; cisplatin.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / physiopathology
  • Animals
  • Apoptosis / drug effects
  • Arginine / administration & dosage
  • Arginine / analogs & derivatives*
  • Arginine / chemistry
  • Cisplatin / adverse effects*
  • Creatinine / metabolism
  • Drugs, Chinese Herbal / administration & dosage*
  • Drugs, Chinese Herbal / chemistry
  • Glucose / administration & dosage*
  • Glucose / chemistry
  • Glycine / administration & dosage
  • Glycine / analogs & derivatives*
  • Glycine / chemistry
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism
  • Maillard Reaction
  • Male
  • Mice, Inbred ICR
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Oxidative Stress / drug effects
  • Panax / chemistry*
  • Phosphatidylinositol 3-Kinase / genetics
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects

Substances

  • Drugs, Chinese Herbal
  • NF-kappa B
  • arginyl-fructosyl-glucose
  • fructosyl-glycine
  • Arginine
  • Creatinine
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • Glucose
  • Cisplatin
  • Glycine