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The ancient Chinese formula Longdan Xiegan Tang improves antipsychotic-induced hyperprolactinemia by repairing the hypothalamic and pituitary TGF-β1 signaling in rats.

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机构： [1]Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China [2]Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW, 2000, Australia [3]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China

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关键词： Dopamine Estrogen receptor Longdan Xiegan Tang Olanzapine TGF-β1

摘要：

Antipsychotics often induce hyperprolactinemia. The transforming growth factor (TGF)-beta1 signaling in the pituitary and hypothalamus inhibits prolactin synthesis and secretion, and its impairment is implicated in neuropsychiatric disorders. Longdan Xiegan Tang (LXT) alone or together with antipsychotics have been used to treat various neuropsychiatric diseases and hyperprolactinemia-associated disorders. To investigate the effect of LXT on hyperprolactinemia and involvement of the TGF-beta1 signaling. Male rats were co-administered with olanzapine (5 mg/kg) and LXT extract (50 and 500 mg/kg) (p.o., × 8 weeks). Plasma concentrations of prolactin and TGF-beta1 were determined by ELISA. Protein expression was analyzed by Western blot. Treatment of rats with LXT extract suppressed olanzapine-induced increase in plasma prolactin concentration and overexpression of pituitary and hypothalamic prolactin protein. Importantly, LXT restored olanzapine-induced decrease in protein expression of the key components of the TGF-beta1 signaling, TGF-beta1, type II TGF-beta receptor, type I TGF-beta receptor and phosphorylated SMAD3 in the pituitary and hypothalamus. Further, it antagonized downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein level, and inhibited pituitary estrogen receptor (ER) alpha and ERbeta protein expression. The present results suggest that LXT ameliorates antipsychotic-induced hyperprolactinemia in rats by repairing the pituitary and hypothalamic TGF-beta1 signaling possibly via D2R, ERs or/and other pathways. Our findings may also provide scientific elucidation for use of the ancient Chinese formula to treat the impaired TGF-beta1 signaling-associated neuropsychiatric disorders. Copyright © 2020 Elsevier B.V. All rights reserved.

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出版当年[2019]版：

大类 | 3 区医学

小类 | 2 区全科医学与补充医学 2 区植物科学 3 区药物化学 3 区药学

最新[2025]版：

大类 | 2 区医学

小类 | 1 区全科医学与补充医学 1 区药学 2 区药物化学 2 区植物科学

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第一作者机构： [1]Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

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通讯机构： [1]Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China [2]Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW, 2000, Australia [3]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China [*1]Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China [*2]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China

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The ancient Chinese formula Longdan Xiegan Tang improves antipsychotic-induced hyperprolactinemia by repairing the hypothalamic and pituitary TGF-β1 signaling in rats.

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