Abstract
Purpose: To investigate the anti-hyperprolactinemia effect and mechanism of action of of Alisma plantago-aquatica Linn. extract (APLE) in rats.
 Methods: The hyperprolactinemia (hyperPRL) model of rats was established by intraperitoneal (i.p.) metoclopramide (200 mg/kg daily) for 10 days. Sixty rats were divided into six groups (n = 10 each): normal group), hyperPRL control group, hyperPRL plus 0.6 mg/kg bromocriptine (as a positive control) group, and hyperPRL plus high (14.4 g/kg), medium (7.2 g/kg), or low (3.6 g/kg) dose of APLE. Bromocriptine or vehicle control was administered to the rats daily for 30 days, and the hypothalamus dopamine D2 receptor, protein kinase A (PKA), and cyclic adenosine monophosphate (cAMP) levels were investigated by Western blot.
 Results: Compared with the normal rats, hypothalamus dopamine D2 receptor protein expression was significantly lower in hyperPRL rats (p < 0.01), but was changed significantly after 30-day doses (various) of APLE administration (3.6 g/kg, p < 0.05; 7.2 and 14.4 g/kg, p < 0.01). Compared with the control rats, hypothalamus PKA and cAMP levels were significantly higher in hyperPRL rats (p < 0.01). These increases in PKA and cAMP were significantly attenuated by 30-day of bromocriptine treatment or various doses of APLE (p < 0.01).
 Conclusion: The anti-hyperPRL activity of APLE is confirmed from the findings of this study Thus, the plant can potentially be developed into a new anti-hyperprolactinemia drug.
Highlights
Hyperprolactinemia is an hypothalamic–pituitary axis disease which shows that serum prolactin > 25 ng/mL in young women
They belong to the family of seven transmembrane domain G-protein coupled receptors (GPCR) [9,10,11]
Our study result showed that APLE increases hypothalamus DRD2 level and reduced cAMP and PKA expression in the hyperPRL rats
Summary
Hyperprolactinemia (hyperPRL) is an hypothalamic–pituitary axis disease which shows that serum prolactin > 25 ng/mL in young women. Bromocriptine and cabergoline were the only first-line drugs for the treatment of hyperPRL as dopamine D2 receptor agonists. These drugs have achieved significant effect, they bring many adverse effects such as headache, nausea, vomiting and so on. The serum prolactin level of rats decreased significantly when administrated of Alisma plantago-aquatica extract We designed an animal experiment to study the effect and mechanism of APLE on hyperPRL. Female rats (Wistar, weighing 180-200 g) were bought the laboratory animal centre of Anhui medical university, Hefei, Anhui, China.
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