Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, PR China.
Neurosci Lett. 2010 Aug 2;479(3):236-9. doi: 10.1016/j.neulet.2010.05.069. Epub 2010 Jun 1.
The present study aimed to investigate the antidepressant potential of genipin and its possible mechanisms. Mouse models of depression including the forced swimming test (FST) and the tail suspension test (TST) were used to evaluate the effects of genipin. A possible mechanism was explored in the test of antagonism of reserpine-induced ptosis and hypothermia in mice. The contents of monoamine neurotransmitters and their metabolites including epinephrine (NE), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in mice hippocampi were determined by HPLC-ECD. The results showed that intra-gastric administration of genipin at 50, 100, 200mg/kg or fluoxetine at 7.5mg/kg for 7 days significantly reduced the duration of immobility in FST and TST, while it did not affect the locomotor activity in the open field test (OFT). However, the effect was not dose-dependent. When the mice were treated with genipin or fluoxetine for 7 days, both of them could antagonize reserpine-induced ptosis and hypothermia. The 5-HT and NE contents in mice hippocampi were decreased after the peritoneal injection of reserpine at 2.0mg/kg. The pre-treatment with genipin at 50, 100, 200mg/kg or fluoxetine at 7.5mg/kg for 7 days could elevate the contents of NE and 5-HT in mice hippocampi significantly. The results suggest that compared with fluoxetine, genipin exerts antidepressant-like effects significantly. A possible mechanism, at least in part, is the regulation of the 5-HT and NE levels in the hippocampus.
本研究旨在探讨京尼平的抗抑郁作用及其可能的机制。采用强迫游泳试验(FST)和悬尾试验(TST)两种抑郁模型小鼠评价京尼平的作用,并用利血平致眼睑下垂和体温降低实验测试其对单胺递质的影响。采用 HPLC-ECD 法测定小鼠海马中单胺递质及其代谢产物肾上腺素(NE)、5-羟色胺(5-HT)和 5-羟吲哚乙酸(5-HIAA)的含量。结果显示,连续 7 天灌胃给予京尼平 50、100、200mg/kg 或氟西汀 7.5mg/kg,可显著减少 FST 和 TST 中小鼠不动时间,而对旷场实验中小鼠的自发活动无影响,且无明显的量效关系;连续 7 天给予京尼平或氟西汀,均可对抗利血平所致的眼睑下垂和体温降低;利血平 2.0mg/kg 腹腔注射可降低小鼠海马中 5-HT 和 NE 含量,而连续 7 天预先给予京尼平 50、100、200mg/kg 或氟西汀 7.5mg/kg 可显著升高其含量。结果提示,与氟西汀相比,京尼平具有更显著的抗抑郁作用,其机制可能与调节海马中单胺递质水平有关。