北京中医药2025，Vol.44Issue(11)：1416-1426,11.DOI:10.16025/j.1674-1307.2025.11.009
基于网络药理学、分子对接及动物实验研究宁坤解郁汤治疗围绝经期焦虑状态的药效及作用机制
Efficacy and mechanisms of Ningkun Jieyu Decoction in the treatment of perimenopausal anxiety based on network pharmacology,molecular docking,and animal experiments
摘要
Abstract
Objective To investigate the intervention effects and underlying mechanisms of Ningkun Jieyu Decoction(NKJY)on perimenopausal anxiety(PA).Methods Network pharmacology was employed to screen the active components and targets of NKJY,construct a protein-protein interaction(PPI)network,and perform enrichment analysis of key pathways,followed by molecular docking to validate interactions between core components and targets.A PA rat model was established using partial ovariectomy combined with chronic unpredictable mild stimulation(CUMS).Rats were treated with low-,medium-,or high-dose NKJY.Behavioral changes were evaluated using the forced swimming test,open field test,and sucrose preference test.Serum hormone and neurotransmitter levels were measured by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was performed to observe pathological changes in the hippocampus and uterus.Western blot was used to detect protein expression of protein kinase B(AKT1)and estrogen receptor 1(ESR1)in rat hippocampal tissue,and reverse transcription-polymerase chain reaction(RT-PCR)was used to assess AKT1 and ESR1 mRNA expression.Results Network pharmacology identified 195 active components,of which 188 components(including quercetin and kaempferol)acted on 168 common targets,such as JUN,AKT1,and ESR1.Pathway enrichment analysis revealed that these targets were significantly enriched in hormone response pathways and atherosclerosis-related pathways.Molecular docking showed good binding affinity between core components and targets.Medium-and high-dose NKJY significantly improved anxiety-like behaviors in PA rats,as evidenced by reduced immobility time in the forced swimming test and increased locomotor activity in the open field test.NKJY treatment increased serum levels of 5-hydroxytryptamine(5-HT),dopamine(DA),and estradiol(E2),while decreasing follicle-stimulating hormone(FSH)and luteinizing hormone(LH)levels,and restored hippocampal neuronal and endometrial structures.NKJY synergistically ameliorated hippocampal injury and hormonal imbalance by upregulating AKT1 and ESR1 expression.Conclusion NKJY regulates the"neuro-reproductive-vascular"network through multi-target(including AKT1 and ESR1)and multi-pathway mechanisms(including antioxidant,anti-inflammatory,and estrogen signaling pathways).Multiple components,such as baicalein and quercetin,act synergistically to improve anxiety-like behaviors,sex hormone disturbances,and histopathological changes.关键词
宁坤解郁汤/网络药理学/分子对接/动物实验/围绝经期焦虑Key words
Ningkun Jieyu Decoction/network pharmacology/molecular docking/animal experiments/perimenopause anxiety引用本文复制引用
王浩,李浩然,余立群,李文汉,李浩,张佳鑫,朱旭华,张若兰..基于网络药理学、分子对接及动物实验研究宁坤解郁汤治疗围绝经期焦虑状态的药效及作用机制[J].北京中医药,2025,44(11):1416-1426,11.基金项目
北京市中医药科技发展基金(BJZYQN-2023-12) （BJZYQN-2023-12）
中国中医科学院望京医院苗圃培育计划(WJYY-YJKT-2022-06) （WJYY-YJKT-2022-06）
中国中医科学院望京医院高水平中医医院建设项目(WJCXTD-202403) （WJCXTD-202403）
