Dai Guo-Liang, Yang Xin-Yi, Chen Shan-Shan, Wang Yi-Qing, Liu Mei-Chen, Cao Yang, Li Fei-Ran, Ma Cheng-Yao, Ju Wen-Zheng
Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing 210029, China.
Zhongguo Zhong Yao Za Zhi. 2021 Dec;46(24):6511-6519. doi: 10.19540/j.cnki.cjcmm.20210816.402.
The present study investigated the effects and mechanisms of Jiaotai Pills on depressed mice induced by chronic unpredictable mild stress(CUMS). The CUMS-induced depression model mice were established and the depression behaviors of mice were evaluated by sucrose preference test, open field test, tail suspension test, and forced swimming test. Molecular docking was employed to simulate the interaction of six main active ingredients in Jiaotai Pills with SIRT1. Immunohistochemical staining was used to detect the level of SIRT1 in the hippocampus of mice. Western blot was used to detect the protein expression levels of SIRT1, p-NF-κB p65, NF-κB p65, and FoxO1 in the hippocampus of mice. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the levels of interleukin(IL)-1β, IL-6, tumor necrosis factor-α(TNF-α), and brain-derived neurotrophic factor(BDNF) in the hippocampus and serum of mice. Biochemical kits were used to detect superoxide dismutase(SOD) activity and malondialdehyde(MDA) and glutathione(GSH) levels in the hippocampus and serum of mice. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to detect the levels of dopamine(DA), 5-hydroxytryptamine(5-HT), and norepinephrine(NE) in the hippocampus and serum of mice. The results showed that the sucrose preference rate, movement distance, and the number of crossing centers were reduced in the model group(P<0.01), and the tail suspension time and swimming immobility time were increased(P<0.01). Molecular docking results indicated good binding of six main active ingredients in Jiaotai Pills to SIRT1. In the hippocampus, the expression level of SIRT1 was reduced(P<0.01), and the levels of p-NF-κB p65/NF-κB p65 and FoxO1 were increased(P<0.01). In the hippocampus and serum, the levels of IL-1β, IL-6, TNF-α, and MDA were increased(P<0.01), and the activity of SOD and the levels of GSH, DA, 5-HT, NE, and BDNF were reduced(P<0.01). The treatment with high-dose Jiaotai Pills increased the sucrose preference rate, movement distance, and the number of crossing centers(P<0.05), reduced tail suspension time and swimming immobility time(P<0.01), elevated hippocampal SIRT1 expression level(P<0.01), decreased hippocampal and serum IL-1β, IL-6, TNF-α, and MDA levels(P<0.01), potentiated SOD activity, and up-regulated GSH, DA, 5-HT, NE, and BDNF levels in the hippocampus and serum(P<0.05, P<0.01) in model mice. In conclusion, the results showed that Jiaotai Pills could improve the depression behaviors of model mice with CUMS-induced depression, and the underlying mechanism was related to the up-regulation of SIRT1 in the hippocampus of mice to exert anti-inflammatory and anti-oxidative stress effects.
本研究探讨了交泰丸对慢性不可预测轻度应激（CUMS）诱导的抑郁小鼠的影响及其作用机制。建立了CUMS诱导的抑郁模型小鼠，并通过蔗糖偏好试验、旷场试验、尾悬架试验和强迫游泳试验评估小鼠的抑郁行为。采用分子对接模拟交泰丸中六种主要活性成分与SIRT1的相互作用。采用免疫组织化学染色检测小鼠海马中SIRT1的水平。采用蛋白质免疫印迹法检测小鼠海马中SIRT1、p-NF-κB p65、NF-κB p65和FoxO1的蛋白表达水平。使用酶联免疫吸附测定（ELISA）试剂盒检测小鼠海马和血清中白细胞介素（IL）-1β、IL-6、肿瘤坏死因子-α（TNF-α）和脑源性神经营养因子（BDNF）的水平。使用生化试剂盒检测小鼠海马和血清中超氧化物歧化酶（SOD）活性以及丙二醛（MDA）和谷胱甘肽（GSH）水平。采用液相色谱-串联质谱（LC-MS/MS）检测小鼠海马和血清中多巴胺（DA）、5-羟色胺（5-HT）和去甲肾上腺素（NE）的水平。结果显示，模型组小鼠的蔗糖偏好率、运动距离和穿越中心次数减少（P<0.01），尾悬架时间和游泳不动时间增加（P<0.01）。分子对接结果表明交泰丸中六种主要活性成分与SIRT1具有良好的结合。在海马中，SIRT1的表达水平降低（P<0.01），p-NF-κB p65/NF-κB p65和FoxO1的水平升高（P<0.01）。在海马和血清中，IL-1β、IL-6、TNF-α和MDA的水平升高（P<0.01），SOD活性以及GSH、DA、5-HT、NE和BDNF的水平降低（P<0.
Zhongguo Zhong Yao Za Zhi. 2021-12
Zhongguo Zhong Yao Za Zhi. 2023-4
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