School of Traditional Chinese Medicine, Research Base of Traditional Chinese Medicine Syndrome, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Fuzhou, 350122, People's Republic of China.
Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, People's Republic of China.
Mol Neurobiol. 2024 Mar;61(3):1655-1672. doi: 10.1007/s12035-023-03615-1. Epub 2023 Sep 26.
In this study, we used Chaihu Shugan San (CSS), a traditional Chinese herbal formula, as a probe to investigate the involvement of brain functional network connectivity and hippocampus energy metabolism in perimenopausal depression. A network pharmacology approach was performed to discover the underlying mechanisms of CSS in improving perimenopausal depression, which were verified in perimenopausal depression rat models. Network pharmacology analysis indicated that complex mechanisms of energy metabolism, neurotransmitter metabolism, inflammation, and hormone metabolic processes were closely associated with the anti-depressive effects of CSS. Thus, the serum concentrations of estradiol (E), glutamate (Glu), and 5-hydroxytryptamine (5-HT) were detected by ELISA. The brain functional network connectivity between the hippocampus and adjacent brain regions was evaluated using resting-state functional magnetic resonance imaging (fMRI). A targeted metabolomic analysis of the hippocampal tricarboxylic acid cycle was also performed to measure the changes in hippocampal energy metabolism using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CSS treatment significantly improved the behavioral performance, decreased the serum Glu levels, and increased the serum 5-HT levels of PMS + CUMS rats. The brain functional connectivity between the hippocampus and other brain regions was significantly changed by PMS + CUMS processes but improved by CSS treatment. Moreover, among the metabolites in the hippocampal tricarboxylic acid cycle, the concentrations of citrate and the upregulation of isocitrate and downregulation of guanosine triphosphate (GTP) in PMS + CUMS rats could be significantly improved by CSS treatment. A brain functional network connectivity mechanism may be involved in perimenopausal depression, wherein the hippocampal tricarboxylic acid cycle plays a vital role.
在这项研究中，我们使用柴胡疏肝散（CSS）作为探针，研究其对围绝经期抑郁症中海马功能网络连接和海马能量代谢的影响。采用网络药理学方法研究 CSS 改善围绝经期抑郁症的潜在机制，并在围绝经期抑郁症大鼠模型中进行验证。网络药理学分析表明，能量代谢、神经递质代谢、炎症和激素代谢过程的复杂机制与 CSS 的抗抑郁作用密切相关。因此，通过 ELISA 检测血清雌二醇（E）、谷氨酸（Glu）和 5-羟色胺（5-HT）的浓度。采用静息态功能磁共振成像（fMRI）评估海马与相邻脑区之间的脑功能网络连接。还对海马三羧酸循环进行靶向代谢组学分析，通过液相色谱-串联质谱（LC-MS/MS）测量海马能量代谢的变化。CSS 治疗显著改善了 PMS+CUMS 大鼠的行为表现，降低了血清 Glu 水平，增加了血清 5-HT 水平。PMS+CUMS 过程显著改变了海马与其他脑区之间的脑功能连接，但 CSS 治疗可改善这种改变。此外，在海马三羧酸循环的代谢物中，CSS 治疗可显著改善 PMS+CUMS 大鼠中海马柠檬酸浓度以及异柠檬酸的上调和鸟苷三磷酸（GTP）的下调。脑功能网络连接机制可能参与围绝经期抑郁症，其中海马三羧酸循环起着重要作用。
