title: Emoghrelin, a unique emodin derivative in Heshouwu, stimulates growth hormone secretion via activation of the ghrelin receptor.
abstract: BACKGROUND
  Heshouwu, the root of Polygonum multiflorum, is an anti-aging Chinese traditional medicine. Fresh (raw) Heshouwu is commonly converted to processed Heshouwu by specialized heating to alleviate its side effects of diarrhea presumably caused by anthraquinones. However, raw Heshouwu has been noted to be better than processed Heshouwu regarding anti-aging effects. The therapeutic effects of raw Heshouwu on aging-related diseases were somehow similar to the anti-aging effects of growth hormone release induced by ghrelin
  
  
  METHODS
  Major ingredients in the methanol extract from raw Heshouwu were separated and identified. Emodin-8-O-(6'-O-malonyl)-glucoside, a unique anthraquinone glycoside known to be completely eliminated in the conversion process of Heshouwu was isolated. This emodin derivative, tentatively named emoghrelin, was examined for its cytotoxicity and capability of stimulating growth hormone release of rat primary anterior pituitary cells via activation of the ghrelin receptor. Moreover, molecular modeling of emoghrelin docking to the ghrelin receptor was exhibited to explore the possible interaction within the binding pocket.
  
  
  RESULTS
  No apparent cytotoxicity was observed for emoghrelin of 10(-7)-10(-4)M. Similar to growth hormone-releasing hormone-6 (GHRP-6), a synthetic analog of ghrelin, emoghrelin was demonstrated to stimulate growth hormone secretion of rat primary anterior pituitary cells in a dose dependent manner, and the stimulation was inhibited by [d-Arg(1), d-Phe(5), d-Trp(7,9), Leu(11)]-substance P, an antagonist of the ghrelin receptor. Molecular modeling and docking showed that emoghrelin as well as GHRP-6 could fit in and adequately interact with the binding pocket of the ghrelin receptor.
  
  
  CONCLUSIONS
  The results suggest that emoghrelin is a key ingredient accounting for the anti-aging effects of Heshouwu, and possesses great potential to be a promising non-peptidyl analog of ghrelin.
authors.affiliation: Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Yuan-Hao
authors.initials: YH
authors.lastname: Lo
authors.affiliation: Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Tse-Yu
authors.initials: TY
authors.lastname: Chung
authors.affiliation: Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Nan-Hei
authors.initials: NH
authors.lastname: Lin
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Maw-Rong
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Chou
authors.affiliation: Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 402, Taiwan; Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan. Electronic address: TCTZEN@dragon.nchu.edu.tw.
authors.forename: Jason T C
authors.initials: JT
authors.lastname: Tzen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004642:Emodin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D008297:Male; D062105:Molecular Docking Simulation; D009842:Oligopeptides / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000166:cytology; D018517:Plant Roots; D010946:Plants, Medicinal; D028502:Polygonum; D017207:Rats, Sprague-Dawley; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D005960:Glucosides; D009842:Oligopeptides; D054440:Receptors, Ghrelin; C000600919:emodin-8-O-(6'-O-malonyl)glucoside; D013373:Substance P; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone; C045800:substance P, Phe(5)-Trp(7,9)-Leu(11)-; D004642:Emodin
keywords: Emodin; Emoghrelin; Ghrelin; Growth hormone secretion; Heshouwu