College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, China.
Prevention and Treatment Center, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 2):118907. doi: 10.1016/j.jep.2024.118907. Epub 2024 Oct 9.
Panax ginseng (P. ginseng) C. A. Meyer. has been used extensively globally as a medicine. It has a therapeutic effect on sleep and is an attractive alternative for patients with insomnia. The United States Patent of Invention has approved the use of P. ginseng alcohol extract (GAE) in nutraceuticals or food to improve sleep. It has shown promise as an effective therapeutic agent for improving sleep and cognition. However, its mechanism of action is not yet fully understood.
To investigate the therapeutic benefits of GAE on sleep and cognition and its underlying mechanism in aged sleep-deprived rats, with a focus on orexin-mediated autophagy function.
We conducted in vivo tests in an aged sleep-deprivation rat model produced using p-chlorophenylalanine (PCPA) coupled with modified multi-platform method to examine the therapeutic effects and mechanisms of GAE. A pentobarbital sodium-induced sleep test and water maze were used to assess sleep and cognitive performance, respectively. An enzyme-linked immunosorbent assay was used to determine orexin levels and aging and sleep markers in serum and hypothalamic tissues. Hematoxylin-eosin staining and Nissl staining were used to assess histopathological changes, and autophagy levels were assessed using transmission electron microscopy, immunofluorescence. Western blot and immunohistochemical staining were performed to detect the levels of orexin, orexin-receptor proteins, and autophagy-associated proteins to study the effects of GAE on hippocampal neurons, and the underlying mechanisms.
In aged sleep-deprived rats, GAE treatment prolonged sleep duration, improved cognitive function, prevented hippocampal neuronal damage, increased the number of Nissl bodies, improved aging and sleep markers, and enhanced the LC3A/B expression in autophagosomes and neurons. The amount of orexin in serum and hypothalamic tissue and OX1R, OX2R, and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) proteins also reduced, which resulted in the inhibition of the PI3K/Akt/mTOR pathway and activation of the autophagy process.
GAE may reduce hypothalamic orexin secretion and interact with orexin receptors to inhibit the PI3K/Akt/mTOR signalling network and activate autophagy. This may be a potential mechanism of action of GAE in regulating sleep-related cognitive function.
人参（Panax ginseng）C. A. Meyer 已在全球范围内广泛用作药物。它对睡眠有治疗作用，是失眠患者的一种有吸引力的替代药物。美国专利发明已批准将人参醇提取物（GAE）用于营养保健品或食品中以改善睡眠。它已显示出作为改善睡眠和认知的有效治疗剂的潜力。然而，其作用机制尚不完全清楚。
研究 GAE 对睡眠和认知的治疗益处及其在衰老睡眠剥夺大鼠中的潜在机制，重点是食欲素介导的自噬功能。
我们使用 p-氯苯丙氨酸（PCPA）与改良的多平台方法相结合，在衰老睡眠剥夺大鼠模型中进行了体内测试，以检查 GAE 的治疗效果和机制。戊巴比妥钠诱导的睡眠试验和水迷宫分别用于评估睡眠和认知表现。酶联免疫吸附试验用于测定血清和下丘脑组织中食欲素水平以及衰老和睡眠标志物。苏木精-伊红染色和尼氏染色用于评估组织病理学变化，透射电子显微镜、免疫荧光用于评估自噬水平。Western blot 和免疫组织化学染色用于检测食欲素、食欲素受体蛋白和自噬相关蛋白的水平，以研究 GAE 对海马神经元的影响及其潜在机制。
在衰老睡眠剥夺大鼠中，GAE 治疗延长了睡眠时间，改善了认知功能，防止了海马神经元损伤，增加了尼氏体数量，改善了衰老和睡眠标志物，并增强了自噬体和神经元中的 LC3A/B 表达。血清和下丘脑组织中的食欲素以及 OX1R、OX2R 和磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶 B（Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）蛋白的含量也减少了，这导致了 PI3K/Akt/mTOR 通路的抑制和自噬过程的激活。
GAE 可能通过减少下丘脑食欲素的分泌并与食欲素受体相互作用来抑制 PI3K/Akt/mTOR 信号通路并激活自噬。这可能是 GAE 调节与睡眠相关的认知功能的潜在作用机制。
