Tan Jingxuan, Li Xixuan, Zhu Ying, Sullivan Mitchell A, Deng Bin, Zhai Xuejia, Lu Yongning
Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Glycation and Diabetes Group, Mater Research Institute- University of Queensland, The Translational Research Institute, Brisbane, QLD, Australia.
Front Pharmacol. 2022 Jun 13;13:828595. doi: 10.3389/fphar.2022.828595. eCollection 2022.
Shugan Jieyu Capsule (SG) has been widely used in China to treat mild to moderate depression. L. (St John's Wort, SJW) is the main ingredient of SG and has been used as herbal medicine to treat depression in western countries. However, it is known that SJW has low bioavailability and does not easily get through the blood-brain barrier. Therefore, how SG plays an antidepressant effect in the central nervous system (CNS) remains an urgent problem to be solved. Mounting research has described the relationship between antidepressants and intestinal microbiota to illuminate antidepressive mechanisms in the CNS. We aimed to investigate the effects of therapy with SG on the function of gut microbiota and intestinal microbiota in rats with chronic unpredictable mild stress (CUMS)-induced depression. The psychophysiological state and the hypothalamic-pituitary-adrenal axis function of rats are evaluated through behavioral experiments, corticosterone levels, serotonin levels, and adrenal index measurements. 16S rDNA amplicon sequencing is used to test the changes in gut microbiota and make functional predictions of genes. With treatment of SG, the depression-like behaviors of CUMS-induced rats were reversed; the corticosterone levels and the adrenal index decreased significantly; the level of serotonin increased significantly; and the alpha and beta diversity analysis of microbiota showed an increase in the richness and uniformity of the flora were increased. SG regulated the relative abundance of Erysipelotrichaceae, Bifidobacteriaceae, Atopobiaceae, , and ; Linear discriminant analysis effect size analysis demonstrated that Lactobacillaceae (family level), (genus level), (order level), (class level), and (species level) were biomarkers in the SG group samples, and also likely to modulate metabolic pathways, such as those involved in carbohydrate metabolism, amino acid metabolism, and signal transduction. These data clearly illustrated the effect of SG on gut microbiome, thus laying the foundation for uncovering more insights on the therapeutic function of the traditional Chinese antidepressants. The potential of SG on mechanisms of antidepression to alter gut microbiota and intestinal microbiome function exposed to CUMS can be explored.
疏肝解郁胶囊（SG）在中国已被广泛用于治疗轻至中度抑郁症。贯叶连翘是SG的主要成分，在西方国家已被用作治疗抑郁症的草药。然而，已知贯叶连翘的生物利用度低，不易通过血脑屏障。因此，SG如何在中枢神经系统（CNS）中发挥抗抑郁作用仍是一个亟待解决的问题。越来越多的研究描述了抗抑郁药与肠道微生物群之间的关系，以阐明CNS中的抗抑郁机制。我们旨在研究SG治疗对慢性不可预测轻度应激（CUMS）诱导的抑郁症大鼠肠道微生物群功能和小肠微生物群的影响。通过行为实验、皮质酮水平、血清素水平和肾上腺指数测量来评估大鼠的心理生理状态和下丘脑-垂体-肾上腺轴功能。使用16S rDNA扩增子测序来测试肠道微生物群的变化并对基因进行功能预测。通过SG治疗，CUMS诱导的大鼠的抑郁样行为得到逆转；皮质酮水平和肾上腺指数显著降低；血清素水平显著升高；微生物群的α和β多样性分析表明菌群的丰富度和均匀度增加。SG调节了丹毒丝菌科、双歧杆菌科、阿托波菌科等的相对丰度；线性判别分析效应大小分析表明，乳酸杆菌科（科水平）、某属（属水平）、某目（目水平）、某纲（纲水平）和某物种（物种水平）是SG组样本中的生物标志物，也可能调节代谢途径，如参与碳水化合物代谢、氨基酸代谢和信号转导的途径。这些数据清楚地说明了SG对肠道微生物组的影响，从而为揭示更多关于中药抗抑郁药治疗功能的见解奠定了基础。可以探索SG对暴露于CUMS的肠道微生物群和小肠微生物组功能的抗抑郁机制的潜力。
