Water Extract of Fructus Hordei Germinatus Shows Antihyperprolactinemia Activity via Dopamine D2 Receptor

Abstract

Objective. Fructus Hordei Germinatus is widely used in treating hyperprolactinemia (hyperPRL) as a kind of Chinese traditional herb in China. In this study, we investigated the anti-hyperPRL activity of water extract of Fructus Hordei Germinatus (WEFHG) and mechanism of action. Methods. Effect of WEFHG on serum prolactin (PRL), estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and hypothalamus protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) levels of hyperPRL rats were investigated. And effect of WEFHG on PRL secretion, D2 receptors, and dopamine transporters (DAT) was studied in MMQ, GH3, and PC12 cells, respectively. Results. WEFHG reduced the secretion of PRL in hyperPRL rats effectively. In MMQ cell, treatment with WEFHG at 1-5 mg/mL significantly suppressed PRL secretion and synthesis. Consistent with a D2-action, WEFHG did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D2 receptor expression but significantly increased the expression of D2 receptors and DAT in PC12 cells. In addition, WEFHG reduced the cAMP and PKA levels of hypothalamus in hyperPRL rats significantly. Conclusions. WEFHG showed anti-hyperPRL activity via dopamine D2 receptor, which was related to the second messenger cAMP and PKA.

Figure 1

HyperPRL model of rat was prepared by injecting metoclopramide (MCP, 150 mg/kg) for 10 days, followed by treatment with or without bromocriptine (BMT) or WEFHG at different doses for 20 days. Untreated animals served as control. Serum PRL (a), E2 (b), P (c), FSH (d), and LH (e) were measured. Data are expressed as mean ± SEM (n = 10) and analyzed using one-way ANOVA. *P < 0.05 and **P < 0.01 versus model group.

Figure 2

Time-course and dose-dependent effects of WEFHG in suppressing PRL secretion (a) and dose-dependent effects of WEFHG in inhibiting intracellular PRL expression (b) in MMQ cells. For the intracellular PRL expression, the cells were treated with different concentrations of WEFHG for 24 h. Data are expressed as mean ± SEM (n = 3) and analyzed using one- or two-way ANOVA. *P < 0.05 and **P < 0.01 versus 0 mg/mL group.

Figure 3

Effects of 24 hr WEFHG treatment on PRL secretion (a) and synthesis (b) in GH3 cells. Data are expressed as mean ± SEM (n = 3) and analyzed using one-way ANOVA. No significant differences were found in any multiple comparisons.

Figure 4

Effects of 24 h WEFHG treatment on the D2 receptor expressions (a) and DAT expressions (b). Data are expressed as mean ± SEM (n = 4) and analyzed using one-way ANOVA. *P < 0.05 and **P < 0.01 versus 0 mg/mL group.

Figure 5

Hypothalamus PKA levels were measured. Data are expressed as mean ± SEM (n = 10) and analyzed using one-way ANOVA. *P < 0.05 and **P < 0.01 versus model group.

Figure 6

Hypothalamus cAMP levels were measured. Data are expressed as mean ± SEM (n = 10) and analyzed using one-way ANOVA. *P < 0.05 and **P < 0.01 versus model group.