Tang Qin, Chu Haolin, Sun Nan, Fan Xiaoxu, Han Bing, Li Yu, Yu Xue, Li Lina, Wang Xiuli, Liu Liying, Chang Hongsheng
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China; Pharmacy Department, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Longgang District People's Hospital of Shenzhen, Shenzhen, 518172, China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.
J Ethnopharmacol. 2025 Jan 31;340:119268. doi: 10.1016/j.jep.2024.119268. Epub 2024 Dec 18.
Chai Shao Jie Yu Granules (CSJY) is a renowned and time-honored formula employed in clinical practice for the management of various conditions, notably depression. Depression, a prevalent psychiatric disorder, poses challenges with limited effective treatment options. Traditional herbal medicines have garnered increasing attention in the realm of combating depression, being perceived as safer alternatives to pharmacotherapy.
To explore the effects and mechanisms of CSJY in chronic unpredictable mild stress (CUMS)-induced depression.
Rat models of CUMS-induced depression were established, and the rats were randomly allocated into six groups: Control, CUMS, CUMS + Paroxetine (PX), CUMS + CSJY-L, CUMS + CSJY-M, and CUMS + CSJY-H. Throughout the study, the rats' body weight was monitored. Depression-related behaviors were assessed using the sucrose preference test (SPT) and open field test (OFT). High-performance liquid chromatography-mass spectrometry (HPLC-MS) measured monoamine neurotransmitters in the rat cortex and hippocampus. We measured adrenocorticotropic hormone (ACTH), corticosterone (CORT), and corticotropin-release hormone (CRH) levels in rat serum. Additionally, network pharmacology was employed to predict relevant molecular targets and potential mechanisms, followed by in vivo validation. Western blot analysis was conducted to evaluate the protein levels of 5-hydroxytryptamine/serotonin receptor 1A (5-HT1A) and Glutamate (Glu)-related proteins, such as p-GluA1, GluA1, p-GluN1, GluN1, p-GluN2A and GluN2A in the hippocampus.
In behavioral assessments, CUMS rats exhibited depressive behaviors, which were ameliorated by CSJY or PX treatment. Moreover, CSJY or PX treatment increased serotonin (5-HT) levels. It reduced the kynurenine/tryptophan (KYN/TRP) and gamma-aminobutyric acid/glutamate (GABA/Glu) in the hippocampus and cortex, as well as reduced serum levels of ACTH, CORT and CRH. Furthermore, CSJY or PX administration enhanced the decreased expression of p-GluN1/GluN1 while upregulating 5-HT1A and p-GluA1/GluA1 levels in the CUMS group.
CSJY demonstrated the ability to alleviate depressive behaviors in CUMS-induced depression rats, potentially through the inhibition of the hypothalamic-pituitary-adrenal (HPA) axis, modulation of monoamine neurotransmitters, and glutamatergic neurons. These findings suggest that CSJY could serve as a promising treatment option for depression.
柴芍解郁颗粒（CSJY）是一种在临床实践中用于治疗多种病症，尤其是抑郁症的著名且历史悠久的方剂。抑郁症是一种常见的精神障碍，有效治疗选择有限，带来了诸多挑战。传统草药在对抗抑郁症领域越来越受到关注，被视为药物治疗更安全的替代方案。
探讨柴芍解郁颗粒（CSJY）对慢性不可预测轻度应激（CUMS）诱导的抑郁症的影响及作用机制。
建立CUMS诱导的抑郁症大鼠模型，并将大鼠随机分为六组：对照组、CUMS组、CUMS + 帕罗西汀（PX）组、CUMS + CSJY低剂量组、CUMS + CSJY中剂量组和CUMS + CSJY高剂量组。在整个研究过程中，监测大鼠体重。使用蔗糖偏好试验（SPT）和旷场试验（OFT）评估与抑郁相关的行为。采用高效液相色谱 - 质谱联用（HPLC - MS）测定大鼠皮质和海马中的单胺类神经递质。我们测定大鼠血清中促肾上腺皮质激素（ACTH）、皮质酮（CORT）和促肾上腺皮质激素释放激素（CRH）水平。此外，采用网络药理学预测相关分子靶点和潜在机制，随后进行体内验证。进行蛋白质免疫印迹分析以评估海马中5 - 羟色胺/血清素受体1A（5 - HT1A）和谷氨酸（Glu）相关蛋白，如p - GluA1、GluA1、p - GluN1、GluN1、p - GluN2A和GluN2A的蛋白水平。
在行为评估中，CUMS大鼠表现出抑郁行为，CSJY或PX治疗可改善这些行为。此外，CSJY或PX治疗可提高血清素（5 - HT）水平。它降低了海马和皮质中的犬尿氨酸/色氨酸（KYN/TRP）和γ - 氨基丁酸/谷氨酸（GABA/Glu），以及降低了血清中ACTH、CORT和CRH水平。此外，CSJY或PX给药增强了CUMS组中p - GluN1/GluN1降低的表达，同时上调了5 - HT1A和p - GluA1/GluA1水平。
柴芍解郁颗粒（CSJY）显示出减轻CUMS诱导的抑郁症大鼠抑郁行为的能力，可能是通过抑制下丘脑 - 垂体 - 肾上腺（HPA）轴、调节单胺类神经递质和谷氨酸能神经元实现的。这些发现表明CSJY可能是一种有前景的抑郁症治疗选择。
