Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, PR China.
Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, 210014, PR China.
J Ethnopharmacol. 2020 May 23;254:112713. doi: 10.1016/j.jep.2020.112713. Epub 2020 Feb 25.
Zoujin pill (ZJP), a medication used to treat gastrointestinal disorders since the 15th Century in China, have been reported to exert anti-depressant effects in various models.
To assess the effects of ZJP on gastrointestinal function and depressive behavior in rats under chronic unpredictable mild stress (CUMS), and to examine the underlying mechanisms related to brain-gut axis.
The rats suffered the stressor once daily for 5 weeks. ZJP (0.6 and 1.2 g/kg) and fluoxetine (15 mg/kg) as positive control were administered to the rats through gastric intubation once daily for 5 consecutive weeks. The anti-depression effects were compared by performing sucrose preference tests and open field tests. Gastrointestinal motility was investigated by determining the gastrointestinal transit rate and by electrogastrogram. The serum levels of the gastrointestinal hormone (GAS, MOT, VIP, SP), inflammatory cytokine (IL-1β, IL-6; , TNFα) and glucagon-like peptide-1 (GLP-1) were assayed by enzyme-linked immunosorbent assay. For monoamine neurotransmitters (NE, 5-HT, DA), the levels were determined by high-performance liquid chromatography and electrochemical detection in conjunction, which was applied on the samples taken from the hypothalamus, hippocampus, and striatum.
The depression-like symptoms among rats under CUMS were significantly relieved by ZJP administration (0.6 and 1.2 g/kg). Gastrointestinal motility was also improved by restoring gastric electrical rhythm and promoting gastrointestinal propulsion. The ZJP at 0.6 g/kg dosage obviously up-regulated 5-HT and DA levels in hippocampus. The ZJP at 1.2 g/kg dosage could increase 5-HT and DA levels in hypothalamus, striatum, and hippocampus, while down-regulated the NE level in hypothalamus and hippocampus. ZJP also reversed the alterations in serum gastrointestinal hormones. Furthermore, treatment with ZJP significantly reduced levels of IL-1β, IL-6 and TNF-α and increased serum GLP-1 compared with the CUMS group. Fluoxetine also exerted similar anti-depressant effects in the absence of effects on gastrointestinal motility and the levels of serum hormone, inflammatory cytokine and GLP-1.
ZJP imposed anti-depressant and gastrointestinal regulating functions in rats under CUMS, suggesting potential clinical application. .
自 15 世纪以来，中国就一直使用胄进丸（ZJP）来治疗胃肠道疾病，据报道，它在各种模型中具有抗抑郁作用。
评估 ZJP 对慢性不可预测轻度应激（CUMS）大鼠胃肠功能和抑郁行为的影响，并研究与脑-肠轴相关的潜在机制。
大鼠每天接受一次应激刺激，持续 5 周。ZJP（0.6 和 1.2 g/kg）和氟西汀（15 mg/kg）作为阳性对照，通过胃内插管每天连续给药 5 周。通过蔗糖偏好试验和旷场试验比较抗抑郁作用。通过测定胃肠传递率和胃电图来研究胃肠动力。通过酶联免疫吸附试验测定胃肠激素（GAS、MOT、VIP、SP）、炎症细胞因子（IL-1β、IL-6、TNFα）和胰高血糖素样肽-1（GLP-1）的血清水平。应用高效液相色谱和电化学检测相结合的方法，测定下丘脑、海马和纹状体样本中的单胺神经递质（NE、5-HT、DA）水平。
CUMS 大鼠的抑郁症状明显减轻，ZJP （0.6 和 1.2 g/kg）给药。胃肠动力也通过恢复胃电节律和促进胃肠推进得到改善。ZJP（0.6 g/kg 剂量）可明显上调海马 5-HT 和 DA 水平。ZJP（1.2 g/kg 剂量）可增加下丘脑、纹状体和海马中的 5-HT 和 DA 水平，同时降低下丘脑和海马中的 NE 水平。ZJP 还逆转了血清胃肠激素的变化。此外，与 CUMS 组相比，ZJP 治疗显著降低了血清中白细胞介素-1β、白细胞介素-6 和肿瘤坏死因子-α的水平，并增加了血清 GLP-1 水平。氟西汀在不影响胃肠动力和血清激素、炎症细胞因子和 GLP-1 水平的情况下，也表现出类似的抗抑郁作用。
ZJP 对 CUMS 大鼠具有抗抑郁和胃肠调节作用，提示其具有潜在的临床应用价值。
