中药药理与临床2025，Vol.41Issue(11)：27-33,7.
基于网络药理学和实验验证探究元胡止痛滴丸对CUMS大鼠抗抑郁作用及机制
Network Pharmacology and Animal Experiments Reveal Antidepressant Effect and Mechanism of Yuanhu Zhitong Dropping Pills on CUMS in Rats
摘要
Abstract
Objective:To explore the antidepressant effect and mechanism of Yuanhu Zhitong(元胡止痛)Dropping Pills via network pharmacology and animal experiments.Methods:Network pharmacology was employed to obtain possible targets and signaling pathways of Yuanhu Zhitong Dropping Pills in the treatment of depression.In animal experiments,60 rats were randomly grouped as follows:normal control,model control,Yuanhu Zhitong Dropping Pills(0.38,0.75,and 1.5 g/kg),and positive drug(fluoxetine hydrochloride capsules,3.3 mg/kg).Chronic un-predictable mild stimulation(CUMS)combined with solitary care method was used for the modeling of depression in rats.The sucrose prefer-ence test,forced swimming test,and Morris water maze test were performed on days 15 and 30.After the last administration,the hippocampal tissue of rats was taken for Western blot to determine the protein levels of calmodulin(CaM),calmodulin kinase Ⅱ(Camk Ⅱ),cyclic adeno-sine phosphate responsive element binding protein(CREB),and p-CREB.RT-qPCR was employed to determine the mRNA levels of Cam,Camk Ⅱ,and Creb.Nissl's staining was conducted to reveal neuronal damage in the hippocampal tissue.Results:A total of 75 active ingredi-ents and 94 potential targets were predicted for the antidepressant effect of Yuanhu Zhitong Dropping Pills.The protein-protein interaction network revealed that estrogen receptor 1(ESR1),tyrosine protein kinase SRC(SRC),and prostaglandin G/H synthase 2(PTGS2)were the key targets among the common targets shared by depression and Yuanhu Zhitong Dropping Pills.The cellular components(CC)of GO en-richment analysis involved dendrite,dendritic tree,postsynapse,etc.The biological processes(BP)involved response to hormone,cellular re-sponse to nitrogen compound,circulatory process,etc.Molecular functions(MF)involved oxidoreductase activity,protein domain-specific binding,protein kinase activity,etc.KEGG enrichment analysis predicted the following key pathways:neuroactive ligand-receptor interactions,pathways in cancer,calcium signaling pathway,PI3K AKT signaling pathway,cGMP PKG signaling pathway,etc.The results of animal experi-ments showed that compared with the normal control group,the model control group presented decreased sucrose preference ratio(％),in-creased immobility time in forced swimming,increased escape latency in water maze,reduced number of crossings,down-regulated protein lev-els of CaM,Camk Ⅱ,and p-CREB and mRNA levels of Cam and Camk Ⅱ in the hippocampal tissue(P<0.05 or P<0.01).In addition,the hippocampal CA3 zone of rats in the model control group showed inconsistent sizes and sparse and irregular arrangement of pyramidal cells,re-duced nissl bodies,and light staining.Compared with the model control group,Yuanhu Zhitong Dropping Pills at 0.75 g/kg and 1.5 g/kg in-creased the sucrose preference rate on day 15(P<0.05 or P<0.01),while Yuanhu Zhitong Dropping Pills at all the three doses increased the sucrose preference rate on day 30(P<0.05 or P<0.01).In the forced swimming test,Yuanhu Zhitong Dropping Pills at 1.5 g/kg shortened the immobility time on day 15(P<0.01),and that at all the three doses reduced the immobility time on day 30(P<0.05 or P<0.01).In the Morris water maze test,Yuanhu Zhitong Dropping Pills at 0.75 g/kg and 1.5 g/kg reduced the escape latency and increased the number of crossings on day 15(P<0.05 or P<0.01).On day 30,the two groups showed reduced escape latency and Yuanhu Zhitong Dropping Pills at all the three doses increased the number of crossings(P<0.05 or P<0.01).Yuanhu Zhitong Dropping Pills at 0.75 g/kg and 1.5 g/kg up-regulated the protein levels of CaM,Camk Ⅱ,and p-CREB(P<0.01),while that at all the three doses up-regulated the mRNA levels of Cam and Camk Ⅱ(P<0.05 or P<0.01).The hippocampal CA3 zone in Yuanhu Zhitong Dropping Pills(0.38 g/kg and 0.75 g/kg)groups showed increased number and regular and neat arrangement of pyramidal cells,and that in the 1.5 g/kg group presented pyramidal cells with consistent size and even,neat,and regular arrangement,as well as Nissl bodies with normal morphology and deepened staining.Conclusion:Yuanhu Zhitong Dropping Pills may exert the antidepressant effect by up-regulating the CaM/Camk Ⅱ/CREB signaling pathway and alleviating neuronal damage in the hippocampal tissue.关键词
元胡止痛滴丸/抑郁症/慢性不可预知温和刺激/网络药理学/钙信号通路/行为学Key words
Yuanhu Zhitong(元胡止痛)Dropping Pills/Depression/Chronic unpredictable mild stimulation/Network pharmacology/Calcium signaling pathway/Behavioral studies引用本文复制引用
马骏,胡佳惠,王怀弟,郭影,刘兴国,李坚,刘亚鹏,任一杰,贾继禧..基于网络药理学和实验验证探究元胡止痛滴丸对CUMS大鼠抗抑郁作用及机制[J].中药药理与临床,2025,41(11):27-33,7.基金项目
甘肃省药品监督管理局科研项目(编号:2023GSMPA025) （编号:2023GSMPA025）
甘肃省中医药管理局科研项目(编号:GZKZ-2023-41) （编号:GZKZ-2023-41）
兰州市科技局人才创新创业项目(编号:2022-RC-15). （编号:2022-RC-15）
