Echinacoside Isolated from Cistanche tubulosa Putatively Stimulates Growth Hormone Secretion via Activation of the Ghrelin Receptor

Molecules. 2019 Feb 17;24(4):720. doi: 10.3390/molecules24040720.


Cistanche species, the ginseng of the desert, has been recorded to possess many biological activities in traditional Chinese pharmacopoeia and has been used as an anti-aging medicine. Three phenylethanoid glycosides-echinacoside, tubuloside A, and acteoside-were detected in the water extract of Cistanche tubulosa (Schenk) R. Wight and the major constituent, echinacoside, was further purified. Echinacoside of a concentration higher than 10-6 M displayed significant activity to stimulate growth hormone secretion of rat pituitary cells. Similar to growth hormone-releasing hormone-6, a synthetic analog of ghrelin, the stimulation of growth hormone secretion by echinacoside was inhibited by [D-Arg¹, D-Phe⁵, D-Trp7,9, Leu11]-substance P, an inverse agonist of the ghrelin receptor. Molecular modeling showed that all the three phenylethanoid glycosides adequately interacted with the binding pocket of the ghrelin receptor, and echinacoside displayed a slightly better interaction with the receptor than tubuloside A and acteoside. The results suggest that phenylethanoid glycosides, particularly echinacoside, are active constituents putatively responsible for the anti-aging effects of C. tubulosa and may be considered to develop as non-peptidyl analogues of ghrelin.

Keywords: cistanche tubulosa; echinacoside; ghrelin; growth hormone secretion; phenylethanoid glycosides.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Chromatography, Liquid
  • Cistanche / chemistry*
  • Cistanche / metabolism
  • Glycosides / chemistry
  • Glycosides / isolation & purification*
  • Glycosides / pharmacology*
  • Growth Hormone / biosynthesis*
  • Male
  • Mass Spectrometry
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Rats
  • Receptors, Ghrelin / agonists*


  • Glycosides
  • Plant Extracts
  • Receptors, Ghrelin
  • Growth Hormone
  • echinacoside