Pharmaceutical Department of The First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou, 510080, P.R. China.
Guangdong Provincial Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, P.R. China.
Sci Rep. 2017 Jul 24;7(1):6266. doi: 10.1038/s41598-017-06552-x.
The present study aimed to investigate the mechanisms underlying the antidepressant-like effects of puerarin via the chronic unpredictable stress (CUS) procedure in rats. Similar to Sertraline (Ser), Chronic treatment of puerarin (60 and 120 mg/kg, i.g) elicited the antidepressant-like effects by reversing the decreased sucrose preference in sucrose preference test (SPT), by blocking the increased latency to feed in novelty-suppressed feeding test (NSFT) and the increased immobility time in forced swimming test (FST) without affecting locomotor activity. However, acute puerarin treatment did not ameliorate the antidepressant- and anxiolytic- like effects in FST and NSFT, respectively. In addition, enzyme linked immunosorbent assay (ELISA) and high performance liquid chromatography-electrochemical detection (HPLC-ECD) showed that chronic treatment of puerarin (60 and 120 mg/kg, i.g) reversed the decreased levels of progesterone, allopregnanolone, serotonin (5-HT) and 5-Hydroxyindoleacetic acid (5-HIAA) in prefrontal cortex and hippocampus of post-CUS rats. Furthermore, puerarin (60 and 120 mg/kg, i.g) blocked the increased corticotropin releasing hormone (CRH), corticosterone (Cort) and adrenocorticotropic hormone (ACTH). Collectively, repeated administration of puerarin alleviated the behavioral deficits induced by chronic stress which was associated with the biosynthesis of neurosteroids, normalization of serotonergic system and preventing HPA axis dysfunction.
本研究旨在通过慢性不可预测应激（CUS）程序探讨葛根素抗抑郁样作用的机制。与舍曲林（Ser）相似，葛根素（60 和 120mg/kg，ig）的慢性治疗通过逆转蔗糖偏好测试（SPT）中蔗糖偏好降低、新奇抑制性摄食测试（NSFT）中摄食潜伏期延长和强迫游泳测试（FST）中不动时间增加来产生抗抑郁样作用，而不影响运动活性。然而，急性葛根素处理不能分别改善 FST 和 NSFT 中的抗抑郁和抗焦虑样作用。此外，酶联免疫吸附测定（ELISA）和高效液相色谱-电化学检测（HPLC-ECD）显示，慢性葛根素治疗（60 和 120mg/kg，ig）逆转了慢性应激后大鼠前额叶皮质和海马中孕酮、别孕烯醇酮、5-羟色胺（5-HT）和 5-羟吲哚乙酸（5-HIAA）水平的降低。此外，葛根素（60 和 120mg/kg，ig）阻断了促肾上腺皮质激素释放激素（CRH）、皮质酮（Cort）和促肾上腺皮质激素（ACTH）的增加。综上所述，重复给予葛根素可减轻慢性应激引起的行为缺陷，这与神经甾体的生物合成、5-羟色胺能系统的正常化和防止 HPA 轴功能障碍有关。
