Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Daru. 2014 Jan 8;22(1):16. doi: 10.1186/2008-2231-22-16.
Antidepressants have been shown to affect levels of brain-derived neurotrophic factor (BDNF) and VGF (non-acronymic) whose transcriptions are dependent on cAMP response element binding protein (CREB) in long term treatment. The aim of this study was to verify the subacute antidepressant effects of crocin, an active constituent of saffron (Crocus sativus L.), and its effects on CREB, BDNF, and VGF proteins, transcript levels and amount of active, phosphorylated CREB (P-CREB) protein in rat hippocampus.
Crocin (12.5, 25, and 50 mg/kg), imipramine (10 mg/kg; positive control) and saline (1 mL/kg; neutral control) were administered intraperitoneally (IP) to male Wistar rats for 21 days. The antidepressant effects were studied using the forced swimming test (FST) on day 21 after injection. Protein expression and transcript levels of genes in the rat hippocampus were evaluated using western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively.
Crocin significantly reduced the immobility time in the FST. Western blot analysis showed that 25 and 50 mg/kg of crocin increased the levels of CREB and BDNF significantly and dose dependently. All doses of crocin increased the VGF levels in a dose-dependent manner. Levels of p-CREB increased significantly by 50 mg/kg dose of crocin. Only 12.5 mg/kg crocin could significantly increase the transcript levels of BDNF. No changes in CREB and VGF transcript levels were observed in all groups.
These results suggest that crocin has antidepressant-like action by increasing CREB, BDNF and VGF levels in hippocampus.
抗抑郁药已被证明可影响脑源性神经营养因子（BDNF）和 VGF（非首字母缩略词）的水平，其转录依赖于长期治疗中的环磷腺苷反应元件结合蛋白（CREB）。本研究的目的是验证西红花（藏红花 Crocus sativus L.）的活性成分西红花酸（crocin）的亚急性抗抑郁作用及其对 CREB、BDNF 和 VGF 蛋白、转录水平和活性磷酸化 CREB（P-CREB）蛋白的影响。
crocin（12.5、25 和 50mg/kg）、丙咪嗪（10mg/kg；阳性对照）和生理盐水（1mL/kg；中性对照）腹腔内给药（IP）雄性 Wistar 大鼠 21 天。注射后第 21 天，通过强迫游泳试验（FST）研究抗抑郁作用。使用 Western blot 和定量逆转录聚合酶链反应（qRT-PCR）分别评估大鼠海马中的基因蛋白表达和转录水平。
crocin 可显著减少 FST 中的不动时间。Western blot 分析表明，25 和 50mg/kg 的 crocin 显著增加了 CREB 和 BDNF 的水平，且呈剂量依赖性。crocin 的所有剂量均以剂量依赖性方式增加 VGF 水平。50mg/kg 剂量的 crocin 可使 p-CREB 水平显著增加。仅 12.5mg/kg 的 crocin 可显著增加 BDNF 的转录水平。各组 CREB 和 VGF 转录水平均无变化。
这些结果表明，crocin 通过增加海马中的 CREB、BDNF 和 VGF 水平发挥抗抑郁作用。
