Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine,Nanjing University of Chinese Medicine, Nan Jing, Jiangsu Province, China.
Department of Neurology and Rehabilitation, Shanghai Seventh People's Hospital, Shanghai University of TCM, Shanghai, China.
J Ethnopharmacol. 2020 Oct 28;261:113055. doi: 10.1016/j.jep.2020.113055. Epub 2020 Jun 24.
Kai-Xin-San (KXS) has been prescribed by TCM doctors for treating psychiatric diseases with the core symptoms of anhedonia, amnesia, and dizziness. According to the symptoms of patients, KXS series formulae are created by varying the compatible ratio of herbs. Today, these formulae are still used in the clinic to treat major depressive disorders.
We hoped to evaluate the antidepressant-like effect of Kai-Xin-San via regulation of the gut-brain axis.
Standardized extracts of three representative compatible ratios of KXS had been prepared, and quality control of the extracts was performed by HPLC-MS/MS. Chronic unpredictable mild stress (CUMS)-induced depression-like mice were used as the depression animal model. After KXS treatment, the antidepressant-like effects of KXS were assessed by behavioural tests. The gut microbiota compositions in the faeces were determined by 16S rRNA sequencing technology. The levels of LPS, pro-inflammatory cytokines and HPA-axis-related hormones were measured by ELISA kits, and the expression of barrier proteins in the small intestines and prefrontal cortex were determined by Western blot analysis. Furthermore, antibiotics were used to determine the correlation between KXS exerting an antidepressant-like effect and regulating the gut-brain axis.
KXS alleviated depression-like behaviours in CUMS-exposed mice. Furthermore, these parameters were also found to be changed after KXS treatment. Alteration of the gut microbiota composition were found in the small intestines. A decrease in the LPS and the pro-inflammatory cytokines were found in both the small intestine and brain. An increase in the tight junction proteins was found in the gut epithelium barrier and the blood-brain barrier. A decrease in the stress-related hormones was found in the central nervous system. Furthermore, antibiotic treatment attenuated the antidepressant-like effect of KXS in CUMS-exposed mice.
KXS exerted an antidepressant-like effect regulating the gut-brain axis, which included gut micro-environment modification, suppression of neuronal inflammation in the brain and inhibition of HPA axis activation in CUMS-induced depression-like mice.
开心散（KXS）已被中医医生用于治疗以快感缺失、遗忘和头晕为核心症状的精神疾病。根据患者的症状，通过改变草药的兼容比例来创建 KXS 系列配方。如今，这些配方仍在临床上用于治疗重度抑郁症。
我们希望通过调节肠脑轴来评估开心散的抗抑郁样作用。
制备了三种代表性 KXS 兼容比例的标准化提取物，并通过 HPLC-MS/MS 进行提取物的质量控制。采用慢性不可预测轻度应激（CUMS）诱导的抑郁样小鼠作为抑郁动物模型。在 KXS 治疗后，通过行为测试评估 KXS 的抗抑郁样作用。通过 16S rRNA 测序技术测定粪便中的肠道微生物群落组成。通过 ELISA 试剂盒测定 LPS、促炎细胞因子和 HPA 轴相关激素的水平，并通过 Western blot 分析测定小肠和前额叶皮层中屏障蛋白的表达。此外，使用抗生素来确定 KXS 发挥抗抑郁样作用和调节肠脑轴之间的相关性。
KXS 缓解了 CUMS 暴露小鼠的抑郁样行为。此外，还发现这些参数在 KXS 治疗后发生了变化。在小肠中发现了肠道微生物群落组成的改变。在小肠和大脑中均发现 LPS 和促炎细胞因子减少。在肠道上皮屏障和血脑屏障中发现紧密连接蛋白增加。在中枢神经系统中发现应激相关激素减少。此外，抗生素处理减弱了 CUMS 暴露小鼠中 KXS 的抗抑郁样作用。
KXS 通过调节肠脑轴发挥抗抑郁样作用，包括肠道微环境的改变、抑制脑神经元炎症和抑制 HPA 轴在 CUMS 诱导的抑郁样小鼠中的激活。
