Chen Liang, Li Jiaxin, Fang Chengwei, Wang Jiepeng
School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
School of Basic Medical Sciences, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
Metabolites. 2025 Mar 4;15(3):175. doi: 10.3390/metabo15030175.
BACKGROUND/OBJECTIVES: Epilepsy is a common chronic and recurrent neurological disorder that poses a threat to human health, and Schott (ATS), a traditional Chinese medicine, is used to treat it. This study aimed to determine its effects on plasma metabolites. Moreover, the possible mechanism of its intervention in epilepsy was preliminarily explored, combined with network pharmacology.
An epileptic model of rats was established using pentylenetetrazol. The potential targets and pathways of ATS were predicted by network pharmacology. Ultra Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometrynce Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometryance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry and statistical analyses were used to profile plasma metabolites and identify ATS's effects on epilepsy.
Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that ATS was involved in regulating multiple signaling pathways, mainly including the neuroactive ligand-receptor interaction and GABAerGamma-aminobutyrate transaminaseAminobutyrate Transaminaseapse signaling pathway. ATS treatment restored 19 metabolites in epiGamma-aminobutyrate transaminaseminobutyrate Transaminase rats, affecting lysine, histidine, and purine metabolism. GABA-T was found as a new key target for treating epilepsy with ATS. The IC of ATS for inhibiting GABA-T activity was 57.9 μg/mL. Through metabolomic analysis, we detected changes in the levels of certain metabolites related to the GABAergic system. These metabolite changes can be correlated with the targets and pathways predicted by network pharmacology. One of the limitations of this study is that the correlation analysis between altered metabolites and seizure severity remains unfinished, which restricts a more in-depth exploration of the underlying biological mechanisms. In the future, our research will focus on conducting a more in-depth exploration of the correlation analysis between altered metabolites and seizure severity.
These results improved our understanding of epilepsy and ATS treatment, potentially leading to better therapies. The identification of key metabolites and their associated pathways in this study offers potential novel therapeutic targets for epilepsy. By modulating these metabolites, future therapies could be designed to better manage the disorder. Moreover, the insights from network pharmacology can guide the development of more effective antiepileptic drugs, paving the way for improved clinical outcomes for patients.
背景/目的：癫痫是一种常见的慢性复发性神经系统疾病，对人类健康构成威胁，中药石菖蒲（ATS）被用于治疗癫痫。本研究旨在确定其对血浆代谢物的影响。此外，结合网络药理学初步探讨其干预癫痫的可能机制。
使用戊四氮建立大鼠癫痫模型。通过网络药理学预测ATS的潜在靶点和途径。采用超高效液相色谱-四极杆-飞行时间质谱联用技术及统计分析来分析血浆代谢物谱并确定ATS对癫痫的影响。
京都基因与基因组百科全书富集分析显示，ATS参与调节多种信号通路，主要包括神经活性配体-受体相互作用和γ-氨基丁酸转氨酶信号通路。ATS治疗使癫痫大鼠体内19种代谢物恢复正常，影响赖氨酸、组氨酸和嘌呤代谢。发现γ-氨基丁酸转氨酶是ATS治疗癫痫的一个新的关键靶点。ATS抑制γ-氨基丁酸转氨酶活性的半数抑制浓度为57.9μg/mL。通过代谢组学分析，我们检测到与γ-氨基丁酸能系统相关的某些代谢物水平的变化。这些代谢物变化可与网络药理学预测的靶点和途径相关联。本研究的局限性之一是改变的代谢物与癫痫发作严重程度之间的相关性分析尚未完成，这限制了对潜在生物学机制的更深入探索。未来，我们的研究将集中于对改变的代谢物与癫痫发作严重程度之间的相关性分析进行更深入的探索。
这些结果增进了我们对癫痫和ATS治疗的理解，可能带来更好的治疗方法。本研究中关键代谢物及其相关途径的鉴定为癫痫提供了潜在的新治疗靶点。通过调节这些代谢物，未来的治疗方法可以设计得更好地管理该疾病。此外，网络药理学的见解可以指导开发更有效的抗癫痫药物，为改善患者的临床结局铺平道路。
