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目的 筛选黄精中的抗抑郁活性化合物，探讨其对模拟失重引起抑郁的防护作用及机制。方法 通过系统药理学筛选黄精中的潜在抗抑郁天然活性成分及其作用靶点。实验采用后肢尾悬吊大鼠模型，将24只健康雄性SD大鼠随机分为对照组（0.5%羧甲基纤维素钠灌胃）、HLU组（尾悬吊组）和HLU+治疗组（尾悬吊+活性化合物灌胃组），每组8只。尾悬吊28 d后，通过强迫游泳实验和悬尾实验评估大鼠的抑郁行为，采用H&E染色观察海马组织形态学变化，分析活性化合物靶点的基因本体（GO）、京都基因和基因组数据库（KEGG）的富集结果。结果 从黄精中筛选出38种活性化合物，其中芹菜素的口服利用度为23.06%，类药性为0.21。芹菜素在化合物–靶点网络中的度值和中介中心性较高，预测其可能是黄精中抗抑郁的关键成分。在强迫游泳和悬尾实验中，HLU组大鼠的不动时间与对照组相比显著增加，表明抑郁模型构建成功；而与HLU组相比，HLU+芹菜素组大鼠的不动时间显著减少。海马组织的H&E染色结果显示，HLU组的大鼠海马神经元细胞数目显著减少，出现较多神经元皱缩，神经纤维出现较多小空泡；而HLU+治疗组的大鼠海马神经元数量增加，细胞形态得到改善。靶点富集分析表明，芹菜素的靶点主要涉及细胞凋亡调控及癌症相关信号通路。结论 芹菜素能够显著改善尾悬吊模拟失重大鼠的抑郁行为，并对海马组织具有保护作用，可能为治疗航天失重导致的抑郁提供一种新的天然活性药物。
Abstract：Objective To screen antidepressant-active compounds from Polygonati Rhizoma and explore their effects and possible mechanisms against depression induced by simulated weightlessness. Methods A systems pharmacology approach was used to screen potential antidepressant-active compounds and their targets from Polygonati Rhizoma.The hindlimb unloading(HLU) rat model was employed for the study. Twenty-four healthy male Sprague-Dawley rats were randomly divided into three groups: control group(administered 0.5% carboxymethylcellulose by gavage),HLU group(hindlimb unloading), and HLU + treatment group(hindlimb unloading + active compound gavage), with 8 rats in each group. After 28 days of hindlimb unloading, depressive-like behaviors in rats were evaluated using the forced swimming test and tail suspension test. Hippocampal morphology was examined with H&E staining, and GO and KEGG enrichment analyses were conducted on the targets of active compounds. Results A total of 38 active compounds were screened from Polygonati Rhizoma, among which apigenin had an oral bioavailability of 23.06%and a drug-likeness score of 0.21. Compound-target network analysis indicated that apigenin had the highest degree and betweenness centrality values, suggesting it might be the key active component with antidepressant potential in Polygonati Rhizoma. In the forced swimming and tail suspension tests, rats in the HLU group showed a significant increase in immobility time compared to the control group, indicating successful establishment of the depression model.However, compared to the HLU group, rats in the HLU plus apigenin group exhibited significantly reduced immobility time. The H&E staining results of hippocampal tissue showed a significant reduction in the number of hippocampal neurons, along with numerous shrunken neurons and small vacuoles in nerve fibers in the HLU group. In contrast, the treatment group exhibited an increased number of hippocampal neurons, with improved cellular morphology. Target enrichment analysis indicated that apigenin targets were mainly involved in the regulation of apoptosis and cancerrelated signaling pathways. Conclusion Apigenin significantly improved depressive-like behaviors in rats subjected to hindlimb unloading, and it has a protective effect on hippocampal tissue. It may provide a new natural active compound for the treatment of depression caused by spaceflight-induced weightlessness.
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基本信息:
DOI：10.16289/j.cnki.1002-0837.2025.01008
中图分类号:R285.5
引用信息:
[1]邓晓铌,张文娟,余宏等.黄精活性成分芹菜素对抗尾悬吊模拟失重诱发的大鼠抑郁行为研究[J].航天医学与医学工程,2025,36(01):43-49.DOI:10.16289/j.cnki.1002-0837.2025.01008.
基金信息:
中央高校基本科研业务费（D5000230104）