Paeoniflorin ameliorates antipsychotic-induced hyperprolactinemia in rats by attenuating impairment of the dopamine D2 receptor and TGF-ß1 signaling pathways in the hypothalamus and pituitary.
J Ethnopharmacol
; 257: 112862, 2020 Jul 15.
Article
in En
| MEDLINE
| ID: mdl-32294507
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE Paeoniflorin, a prominent component in some Chinese formulas for hyperprolactinemia-associated disorders, has been found to inhibit prolactin secretion in prolactinoma cells. AIM:
To examine the efficacy of paeoniflorin on hyperprolactinemia and the underlying mechanisms of action. MATERIALS ANDMETHODS:
Hyperprolactinemia in female rats was generated by administration of olanzapine (5 mg/kg, by a gavage method, once daily, × 13 weeks). The rats were co-treated with paeoniflorin (10 and 50 mg/kg). Prolactin and TGF-ß1 concentrations were detected by ELISA. Protein expression was determined by Western blot. The effect in MMQ cells was also examined.RESULTS:
Paeoniflorin inhibited olanzapine-induced increases in plasma prolactin concentration and prolactin protein overexpression in the pituitary and hypothalamus of rats. Further, paeoniflorin restored olanzapine-induced downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein expression. More importantly, paeoniflorin attenuated olanzapine-suppressed protein expression of transforming growth factor (TGF)-ß1 and its downstream genes, type II TGF-ß receptor, type I TGF-ß receptor and phosphorylated SMAD3 in the tissues. However, paeoniflorin did not affect plasma TGF-ß1 concentration and hepatic TGF-ß1 protein expression. In accord, olanzapine-induced increase in prolactin concentration, upregulation of prolactin protein expression, and downregulation of protein expression of the D2R and TGF-ß1 signals in MMQ cells were attenuated.CONCLUSIONS:
This study demonstrates that paeoniflorin ameliorates olanzapine-induced hyperprolactinemia in rats by attenuating impairment of the D2R and TGF-ß1 signaling pathways in the hypothalamus and pituitary. Our findings may provide evidence to support the use of paeoniflorin-contained Chinese herbs and formulas for hyperprolactinemia and its associated disorders.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Pituitary Gland
/
Prolactin
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Hyperprolactinemia
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Receptors, Dopamine D2
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Monoterpenes
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Transforming Growth Factor beta1
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Glucosides
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Hypothalamus
Type of study:
Prognostic_studies
Language:
En
Journal:
J Ethnopharmacol
Year:
2020
Type:
Article