The extract of Rhodiolae Crenulatae Radix et Rhizoma induces the accumulation of HIF-1α via blocking the degradation pathway in cultured kidney fibroblasts

Planta Med. 2011 Jun;77(9):894-9. doi: 10.1055/s-0030-1250627. Epub 2010 Dec 14.

Abstract

Rhodiolae Crenulatae Radix et Rhizoma (Rhodiola), the root and rhizome of Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba, has been used as a traditional Chinese medicine (TCM) to increase the body resistance against hypoxia in mountain sickness. The mechanism of this adaptogenic property deriving from Rhodiola, however, has not been revealed. Erythropoietin (EPO) is an erythrocyte-specific hematopoietic hormone that increases the production of red blood cells: this hormone is a crucial factor in regulating the body balance in responding to hypoxia. In cultured kidney fibroblasts (HEK293T), application of water extract deriving from Rhodiola induced the expression of EPO both in mRNA and protein levels. The activation of the Hypoxia Response Element (HRE) located on the promoter region of the EPO gene is one of the mechanisms accounting for transcriptional activation. In addition, the Rhodiola-induced EPO expression was triggered by an increase of hypoxia-inducible factor-1 α (HIF-1 α) protein, via the reduction of HIF-1 α degradation but not the induction of HIF-1 α mRNA. Moreover, the same EPO induction effect by Rhodiola was also observed in cultured liver cells since liver is another vital organ to provide EPO regulation apart from the kidney. These results therefore elucidate one of the molecular mechanisms of this herb in mediating the anti-hypoxia function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Deferoxamine / pharmacology
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Erythropoietin / genetics
  • Erythropoietin / metabolism*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Hypoxia / immunology
  • Hypoxia / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Kidney / cytology
  • Kidney / drug effects*
  • Kidney / metabolism
  • Mixed Function Oxygenases / antagonists & inhibitors
  • Plant Roots / chemistry
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins
  • Response Elements / genetics
  • Rhizome / chemistry
  • Rhodiola / chemistry*
  • Siderophores / pharmacology
  • Transcriptional Activation

Substances

  • Drugs, Chinese Herbal
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Siderophores
  • Erythropoietin
  • Mixed Function Oxygenases
  • Deferoxamine