Department of Chinese Medicine Preparations, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China.
College of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210046, China.
Chin J Integr Med. 2024 Aug;30(8):692-700. doi: 10.1007/s11655-024-3906-2. Epub 2024 May 11.
To explore the rapid antidepressant potential and the underlying mechanism of Chaihu Shugan San (CSS) in female mice.
Liquid chromatography mass spectrometry (LC-MS)/MS was used to determine the content of main components in CSS to determine its stability. Female C57BL/6J mice were randomly divided into 4 groups, including control (saline), vehicle (saline), CSS (4 g/kg) and ketamine (30 mg/kg) groups. Mice were subjected to irregular stress stimulation for 4 weeks to establish the chronic mild stress (CMS) model, then received a single administration of drugs. Two hours later, the behavioral tests were performed, including open field test, tail suspension test (TST), forced swimming test (FST), novelty suppression feeding test (NSF), and sucrose preference test (SPT). Western blot analysis was used to detect the expression levels of N-methyl-D-aspartate receptor (NMDA) subtypes [N-methyl-D-aspartate receptor 1 (NR1), NR2A, NR2B], synaptic proteins [synapsin1 and post synaptic density protein 95 (PSD95)], and brain-derived neurotrophic factor (BDNF). Moreover, the rapid antidepressant effect of CSS was tested by pharmacological technologies and optogenetic interventions that activated glutamate receptors, NMDA.
Compared with the vehicle group, a single administration of CSS (4 g/kg) reversed all behavioral defects in TST, FST, SPT and NSF caused by CMS (P<0.05 or P<0.01). CSS also significantly decreased the expressions of NMDA subtypes (NR1, NR2A, NR2B) at 2 h in hippocampus of mice (all P<0.01). In addition, similar to ketamine, CSS increased levels of synaptic proteins and BDNF (P<0.05 or P<0.01). Furthermore, the rapid antidepressant effects of CSS were blocked by transient activation of NMDA receptors in the hippocampus (all P<0.01).
Rapid antidepressant effects of CSS by improving behavioral deficits in female CMS mice depended on rapid suppression of NMDA receptors and activation of synaptic proteins.
探索柴芍疏肝散（CSS）在雌性小鼠中快速抗抑郁的潜力及其潜在机制。
采用液相色谱-质谱联用（LC-MS/MS）测定 CSS 中主要成分的含量，以确定其稳定性。将雌性 C57BL/6J 小鼠随机分为 4 组，包括对照组（生理盐水）、载体组（生理盐水）、CSS 组（4 g/kg）和氯胺酮组（30 mg/kg）。小鼠接受 4 周的不规则应激刺激，建立慢性轻度应激（CMS）模型，然后给予单次给药。2 小时后进行行为测试，包括旷场试验、悬尾试验（TST）、强迫游泳试验（FST）、新奇抑制摄食试验（NSF）和蔗糖偏好试验（SPT）。Western blot 分析用于检测 N-甲基-D-天冬氨酸受体（NMDA）亚型[N-甲基-D-天冬氨酸受体 1（NR1）、NR2A、NR2B]、突触蛋白[突触素 1 和突触后密度蛋白 95（PSD95）]和脑源性神经营养因子（BDNF）的表达水平。此外，通过药理学技术和光遗传学干预激活谷氨酸受体 NMDA 来测试 CSS 的快速抗抑郁作用。
与载体组相比，CSS（4 g/kg）单次给药可逆转 CMS 引起的 TST、FST、SPT 和 NSF 中所有行为缺陷（均 P<0.05 或 P<0.01）。CSS 还显著降低了海马 NMDA 亚型（NR1、NR2A、NR2B）在 2 小时时的表达（均 P<0.01）。此外，与氯胺酮类似，CSS 增加了突触蛋白和 BDNF 的水平（均 P<0.05 或 P<0.01）。此外，CSS 的快速抗抑郁作用被 NMDA 受体在海马中的瞬时激活所阻断（均 P<0.01）。
CSS 通过改善雌性 CMS 小鼠的行为缺陷而产生的快速抗抑郁作用，依赖于 NMDA 受体的快速抑制和突触蛋白的激活。
