Wang Qi, Zhao Yingxia, Qin Xuemei, Tian Junsheng
Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China.
Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan 030006, China.
Chin Herb Med. 2024 Feb 28;16(4):612-621. doi: 10.1016/j.chmed.2023.12.003. eCollection 2024 Oct.
To decipher the antidepression effect of Chaigui Granules (CGKL) from the relationship between depression and microbial molecules based on multi-omics.
Male SD rats were subjected to chronic unpredictable mild stress (CUMS) for seven weeks. The antidepressants CGKL extract and CGKL were administered for the following four weeks. The behavior test and the content of monoamine neurotransmitters were used to evaluate the efficacy of CGKL. The 16S rRNA sequencing, LC-MS technology and molecular biological techniques were used to explore the pharmacological mechanism of CGKL.
CGKL treatment obviously alleviated the depressive behavioral indicators and regulated the content of monoamine neurotransmitters, and presented dose-dependent manner. CGKL could also improve the arginine metabolism disorder of gut microbiota in the jejunum. Meanwhile, the contents of arginine and its metabolites in the serum and hippocampus were regulated to normal levels. Further investigation indicated that the expression of related rate-limiting enzyme genes and proteins in the hippocampus was validated by qRT-PCR and Western blotting. The results showed that the gut microbiota, metabolites, and genes or proteins of rate-limiting enzymes involved in the arginine pathway were significantly regulated by CGKL.
The present study demonstrates that CGKL might exert antidepressant effects through regulating arginine metabolism, and its mechanism may be related to modulating the gut microbiota and related metabolic enzyme.
基于多组学从抑郁症与微生物分子的关系中解读柴桂颗粒（CGKL）的抗抑郁作用。
雄性SD大鼠接受七周的慢性不可预测温和应激（CUMS）。在接下来的四周给予抗抑郁药CGKL提取物和CGKL。采用行为测试和单胺类神经递质含量来评估CGKL的疗效。运用16S rRNA测序、液相色谱-质谱联用技术（LC-MS）和分子生物学技术来探究CGKL的药理机制。
CGKL治疗明显减轻了抑郁行为指标并调节了单胺类神经递质的含量，且呈剂量依赖性。CGKL还可改善空肠中肠道微生物群的精氨酸代谢紊乱。同时，血清和海马中精氨酸及其代谢产物的含量被调节至正常水平。进一步研究表明，通过实时定量聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法（Western blotting）验证了海马中相关限速酶基因和蛋白质的表达。结果显示，CGKL显著调节了精氨酸途径中涉及的肠道微生物群、代谢产物以及限速酶的基因或蛋白质。
本研究表明，CGKL可能通过调节精氨酸代谢发挥抗抑郁作用，其机制可能与调节肠道微生物群和相关代谢酶有关。
