摘要
越鞠丸治疗抑郁症与心血管疾病的疗效已获得广泛认可。既往研究表明,其可显著改善慢性不可预见性温和应激(CUMS)联合动脉粥样硬化(AS)诱发的抑郁样行为。鉴于双心疾病机制的复杂性,该研究联合代谢组学与网络药理学方法,系统揭示越鞠丸改善双心疾病抑郁症状的作用机制。结果显示,越鞠丸干预后海马体内9种异常代谢物水平恢复至正常范围,主要涉及环磷酸腺苷(cAMP)信号通路、雷帕霉素靶蛋白(mTOR)信号通路、甘氨酸/丝氨酸/苏氨酸代谢及氨酰-tRNA生物合成等关键通路。在高脂饮食诱导的CUMS ApoE-/-小鼠模型中,越鞠丸显著上调海马腺苷一磷酸(AMP)水平,并下调L-丙氨酸与D-甘油酸水平。综上,越鞠丸通过调控甘氨酸/丝氨酸/苏氨酸代谢及cAMP、mTOR等多条代谢轴发挥抗抑郁作用。网络药理学预测表明,其核心活性成分可能通过调节神经炎症与突触可塑性相关通路[如丝氨酸/苏氨酸蛋白激酶1(AKT1)、促分裂原活化蛋白激酶1(MAPK1)、前列腺素内过氧化物合成酶2(PTGS2)等靶点]治疗CUMS合并AS。该研究为越鞠丸缓解双心疾病抑郁症状的临床应用提供了理论依据。
The therapeutic effects of Yueju Pills on depression and cardiovascular diseases have been widely recognized.Previous studies have shown that the drug can significantly improve depressive-like behaviors induced by chronic unpredictable mild stress(CUMS)combined with atherosclerosis(AS).Given the complex pathogenesis of psychocardiac diseases,this study integrated metabolomics and network pharmacology to systematically elucidate the mechanism of Yueju Pills in alleviating depressive symptoms in psychocardiac diseases.The results demonstrate that,after Yueju Pill intervention,the levels of 9 abnormal metabolites in the hippocampus restore to normal ranges,primarily involving key pathways or signaling pathways,including the cyclic adenosine monophosphate(cAMP),mammalian target of rapamycin(mTOR),glycine/serine/threonine metabolism,and aminoacyl-tRNA biosynthesis.In a high-fat diet-induced CUMS ApoE-/-mouse model,Yueju Pills significantly increases adenosine monophosphate(AMP)levels and decreases L-alanine and D-glyceric acid levels in the hippocampus.In conclusion,Yueju Pills exert antidepressant effects by regulating multiple metabolic axes,including glycine/serine/threonine metabolism and the cAMP,mTOR signaling pathways.Network pharmacology predictions reveal that the treatment of CUMS combined with AS by its core active components may be realized through modulating pathways concerning neuroinflammation and synaptic plasticity,including serine/threonine-protein kinase 1(AKT1),mitogen-activated protein kinase 1(MAPK1),and prostaglandin-endoperoxide synthase 2(PTGS2).This study provides a theoretical reference for the clinical application of Yueju Pills in alleviating the depressive symptoms of psychocardiac diseases.
作者
杜成渝
郭雪峰
张瀚文
梁健
张欢
黄国威
倪萍
马海钧
于游
于睿
DU Cheng-yu;GUO Xue-feng;ZHANG Han-wen;LIANG Jian;ZHANG Huan;HUANG Guo-wei;NI Ping;MA Hai-jun;YU You;YU Rui(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;the Second Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110031,China)
出处
《中国中药杂志》
北大核心
2025年第16期4564-4573,共10页
China Journal of Chinese Materia Medica
基金
国家自然科学基金面上项目(82274494)
辽宁省博士科研启动基金计划项目(2023-BS-049)
辽宁省科学技术计划项目(2023JH2/101600030)。
关键词
越鞠丸
代谢组学
网络药理学
双心疾病
抑郁
Yueju Pills
metabolomics
network pharmacology
psychocardiac disease
depressive
