title: Paeoniflorin and liquiritin, two major constituents in Chinese herbal formulas used to treat hyperprolactinemia-associated disorders, inhibits prolactin secretion in prolactinoma cells by different mechanisms.
abstract: BACKGROUND
  Paeoniflorin and liquiritin are major constituents in some Chinese herbal formulas, such as Yiru Tiaojing (YRTJ) Granule (a hospitalized preparation) and Peony-Glycyrrhiza Decoction, used for hyperprolactinemia-associated disorders.
  
  
  OBJECTIVE
  To investigate the effect of paeoniflorin and liquiritin on prolactin secretion.
  
  
  METHODS
  The effect of YRTJ Granule on metoclopramide-induced hyperprolactinemia was tested in rats. Paeoniflorin and liquiritin in the YRTJ Granule extract were identified and quantified by HPLC. The effects of paeoniflorin and liquiritin on prolactin secretion were examined in prolactinoma cells that were identified morphologically and by Western blot. The concentration of prolactin was determined by ELISA. The gene expression was analyzed by Western blot.
  
  
  RESULTS
  YRTJ Granule ameliorated metoclopramide-induced hyperprolactinemia in rats. The contents of paeoniflorin and liquiritin in YRTJ Granule were 7.43 and 2.05mg/g extract, respectively. Paeoniflorin, liquiritin and bromocriptine (a dopamine D2receptor (D2R) agonist) decreased prolactin concentration in MMQ cells expressing D2R. However, the effect of liquiritin and bromocriptine was abolished in GH3 cells lacking D2R expression. Interestingly, paeoniflorin still decreased prolactin concentration in GH3 cells in the same manner. Furthermore, paeoniflorin suppressed prolactin protein expression, and was without effect on D2R protein expression in both MMQ and GH3 cells.
  
  
  CONCLUSIONS
  The present results suggest that paeoniflorin and liquiritin play a role in YRTJ Granule-elicited improvement of hyperprolactinemia. While the effect of liquiritin is D2R-dependent, paeoniflorin D2R-independently inhibits prolactin secretion in prolactinoma cells that may especially benefit the hyperprolactinemic patients who are refractory to dopaminergic therapies.
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: weiyuanyi@163.com.
authors.forename: Yuanyi
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: m13826059869@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: La
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: 1039875614@sitcm.edu.au.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Central Clinical School, Royal Prince Alfred Hospital, The University of Sydney, Australia. Electronic address: robert.batey@uni.sydney.edu.au.
authors.forename: Robert
authors.initials: R
authors.lastname: Batey
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Guangdong Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address: wcxia@hotmail.com.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Wang
authors.affiliation: Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, NSW 2000, Australia. Electronic address: yuhao@sitcm.edu.au.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D006966:Hyperprolactinemia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008787:Metoclopramide; D039821:Monoterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D010911:Pituitary Neoplasms / Q000378:metabolism; D011388:Prolactin / Q000235:genetics / Q000378:metabolism*; D015175:Prolactinoma / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D006027:Glycosides
chemical_list: D004365:Drugs, Chinese Herbal; D044950:Flavanones; D005960:Glucosides; D008787:Metoclopramide; D039821:Monoterpenes; D011388:Prolactin; C015423:peoniflorin; D006027:Glycosides; C512196:liquiritin
keywords: Dopamine D(2) receptor; Hyperprolactinemia; Paeoniflorin