Mou Zheng, Huang Qian, Chu Shi-Feng, Zhang Mei-Jin, Hu Jin-Feng, Chen Nai-Hong, Zhang Jun-Tian
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.
Biomed Pharmacother. 2017 Aug;92:962-971. doi: 10.1016/j.biopha.2017.05.119. Epub 2017 Jun 10.
Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity is a well-established pathological feature of major depression, accompanied by the persistent increase of glucocorticoid level and the dysfunction of hypothalamic-pituitary-gonadal (HPG) axis. Ginsenoside Rg1 (Rg1) is one of the most active ingredients of Panax ginseng, which has various biological activity.
This study aimed to investigate the antidepressive effects of Rg1 and elucidate its impact on neuroendocrine system.
The antidepressive effects of Rg1 were first analysed in mice, and was further identified in the chronic-unpredictable-mild-stress (CUMS) model and the gonadectomized (GDX) model. The effects of Rg1 on depression-like behaviour were analysed by the forced swimming test (FST), tail suspension test (TST), sucrose preference test, and measurement of pentobarbital-induced sleep. The serum corticosterone and testosterone levels were detected by ELISA. The protein levels of glucocorticoid receptor (GR) and androgen receptor (AR) were analysed by western blot and immunohistochemistry analysis.
Rg1 significantly decreased the immobility time of mice in FST and TST. Furthermore, Rg1 alleviated anhedonia and hopelessness, decreased serum corticosterone level, and increased serum testosterone level, and the GR protein level in the PFC and hippocampus of the CUMS-treated rats. Moreover, Rg1 improved sleep disruption, down-regulated the serum corticosterone level, and increased AR protein level in the PFC of the GDX-treated mice.
Together, these studies suggest that Rg1 displayed antidepressant activity through the modulation of the HPA and the HPG axis. These findings provide new mechanism involved in the antidepressive effects of Rg1 and propose theoretical clues for clinical therapies.
下丘脑 - 垂体 - 肾上腺（HPA）轴功能亢进是重度抑郁症公认的病理特征，伴有糖皮质激素水平持续升高以及下丘脑 - 垂体 - 性腺（HPG）轴功能障碍。人参皂苷Rg1（Rg1）是人参最具活性的成分之一，具有多种生物学活性。
本研究旨在探讨Rg1的抗抑郁作用，并阐明其对神经内分泌系统的影响。
首先在小鼠中分析Rg1的抗抑郁作用，并在慢性不可预测轻度应激（CUMS）模型和去势（GDX）模型中进一步验证。通过强迫游泳试验（FST）、悬尾试验（TST）、蔗糖偏好试验和戊巴比妥诱导睡眠测量分析Rg1对抑郁样行为的影响。采用酶联免疫吸附测定（ELISA）检测血清皮质酮和睾酮水平。通过蛋白质免疫印迹和免疫组织化学分析糖皮质激素受体（GR）和雄激素受体（AR）的蛋白水平。
Rg1显著缩短了小鼠在FST和TST中的不动时间。此外，Rg1减轻了快感缺失和绝望情绪，降低了血清皮质酮水平，提高了血清睾酮水平，以及CUMS处理大鼠前额叶皮质（PFC）和海马中的GR蛋白水平。此外，Rg1改善了睡眠障碍，下调了血清皮质酮水平，并提高了GDX处理小鼠PFC中的AR蛋白水平。
总之，这些研究表明Rg1通过调节HPA轴和HPG轴发挥抗抑郁活性。这些发现为Rg1的抗抑郁作用提供了新机制，并为临床治疗提供了理论线索。
