Protective Effects of Processed Ginseng and Its Active Ginsenosides on Cisplatin-Induced Nephrotoxicity: In Vitro and in Vivo Studies

J Agric Food Chem. 2015 Jul 1;63(25):5964-9. doi: 10.1021/acs.jafc.5b00782. Epub 2015 Jun 19.

Abstract

Although cisplatin can dramatically improve the survival rate in cancer patients, its use is limited by its nephrotoxicity. Previous investigations showed that Panax ginseng contains components that exhibit protective activity against cisplatin-induced nephropathy. The aim of the present study is to investigate the effect of microwave-assisted processing on the protective effect of ginseng and identify ginsenosides that are active against cisplatin-induced kidney damage to evaluate the potential of using ginseng in the management of nephrotoxicity. The LLC-PK1 cell damage by cisplatin was significantly decreased by treatment with microwave-processed ginseng (MG) and ginsenosides Rg3, Rg5, and Rk1. Reduced expression of p53 and c-Jun N-terminal kinase proteins by cisplatin in LLC-PK1 cells was markedly ameliorated after Rg3 and Rg5/Rk1 treatment. Additionally, elevated expression of cleaved caspase-3 was significantly reduced by ginsenosides Rg5, Rk1, and with even greater potency, Rg3. Moreover, MG and its fraction containing active ginsenosides showed protective effects against cisplatin-induced nephropathy in mice. We found that ginsenosides Rg3, Rg5, and Rk1 generated during the heat treatment of ginseng ameliorate renal damage by regulating inflammation and apoptosis. Results of current experiments provide evidence of the renoprotective effects and therapeutic potential of MG and its active ginsenosides, both in vitro and in vivo.

Keywords: Panax ginseng; cisplatin; ginsenoside; inflammation; nephrotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line
  • Cisplatin / toxicity*
  • Ginsenosides / administration & dosage*
  • Ginsenosides / pharmacology
  • Humans
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Kidney / drug effects
  • Kidney / injuries
  • Kidney Diseases / etiology
  • Kidney Diseases / genetics
  • Kidney Diseases / metabolism
  • Kidney Diseases / prevention & control*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Panax / chemistry*
  • Protective Agents / administration & dosage*
  • Protective Agents / pharmacology
  • Swine

Substances

  • Ginsenosides
  • Protective Agents
  • ginsenoside Rg5
  • ginsenoside Rk1
  • ginsenoside Rg3
  • JNK Mitogen-Activated Protein Kinases
  • Caspase 3
  • Cisplatin