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.

ETHNOPHARMACOLOGICAL RELEVANCE

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.

AIM OF THE STUDY

To investigate the effect of paeoniflorin and liquiritin on prolactin secretion.

MATERIALS AND 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 D receptor (DR) agonist) decreased prolactin concentration in MMQ cells expressing DR. However, the effect of liquiritin and bromocriptine was abolished in GH3 cells lacking DR 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 DR 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 DR-dependent, paeoniflorin DR-independently inhibits prolactin secretion in prolactinoma cells that may especially benefit the hyperprolactinemic patients who are refractory to dopaminergic therapies.