Efficacy and mechanisms of <italic style="font-style: italic">Ningkun Jieyu Decoction</italic> in the treatment of perimenopausal anxiety based on network pharmacology, molecular docking, and animal experiments

WANG Hao; LI Haoran; YU Liqun; LI Wenhan; LI Hao; ZHANG Jiaxin; ZHU Xuhua; ZHANG Ruolan

doi:10.16025/j.1674-1307.2025.11.009

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Efficacy and mechanisms of Ningkun Jieyu Decoction in the treatment of perimenopausal anxiety based on network pharmacology, molecular docking, and animal experiments

更新时间：2026-01-29

- Efficacy and mechanisms of Ningkun Jieyu Decoction in the treatment of perimenopausal anxiety based on network pharmacology, molecular docking, and animal experiments
- Beijing Journal of Traditional Chinese Medicine Vol. 44, Issue 11, Pages: 1416-1426(2025)
- 作者机构：
  
  1.中国中医科学院望京医院妇科，北京 100102
  2.北京中医药大学，北京 100029
- 作者简介：
- 基金信息：
- DOI：10.16025/j.1674-1307.2025.11.009
  CLC：
- Received：20 November 2024，
  
  Published：25 November 2025
- 稿件说明：
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王浩，李浩然，余立群，等.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.

WANG Hao,LI Haoran,YU Liqun,et al.Efficacy and mechanisms of Ningkun Jieyu Decoction in the treatment of perimenopausal anxiety based on network pharmacology, molecular docking, and animal experiments[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(11):1416-1426.
王浩，李浩然，余立群，等.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. DOI： 10.16025/j.1674-1307.2025.11.009.

WANG Hao,LI Haoran,YU Liqun,et al.Efficacy and mechanisms of Ningkun Jieyu Decoction in the treatment of perimenopausal anxiety based on network pharmacology, molecular docking, and animal experiments[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(11):1416-1426. DOI： 10.16025/j.1674-1307.2025.11.009.

摘要

目的

探讨宁坤解郁汤（NKJY）对围绝经期焦虑（PA）的干预作用及机制。

方法

通过网络药理学筛选NKJY活性成分及靶点，构建蛋白质-蛋白质相互作用（PPI）网络并富集分析关键通路，通过分子对接验证核心成分-靶点互作。采用不完全去势法联合慢性轻度不可预见性应激法（chronic unpredictable mild stimulation，CUMS）复制PA大鼠模型；并用低、中、高剂量组NKJY进行干预。观察大鼠行为学（强迫游泳、旷场、糖水偏好）变化，酶联免疫吸附试验（ELISA）检测血清中激素和神经递质水平，苏木精-伊红（HE）染色观察海马、子宫组织病理变化，Western blotting法检测大鼠海马组织蛋白激酶B（AKT1）/雌激素受体1（ESR1）蛋白表达，逆转录-聚合酶链反应（RT-PCR）法检测大鼠海马组织AKT1、ESR1 mRNA表达。

结果

网络药理学筛选出195个活性成分，其中188个成分（包括槲皮素、山奈酚等）作用于JUN、AKT1、ESR1等168个共同靶点；通路富集分析发现，这些靶点显著富集于激素反应通路、动脉粥样硬化通路等生物过程。分子对接显示核心成分与靶点结合良好。中高剂量NKJY显著改善PA大鼠焦虑行为（缩短强迫游泳不动时间、提高旷场活动度），上调血清五羟色胺（5-HT）、多巴胺（DA）、雌二醇（E2）水平，并降低促卵泡激素（FSH）、促黄体生成素（LH）水平，修复海马神经元及子宫内膜结构。NKJY通过上调AKT1和ESR1，协同改善海马损伤与激素失衡。

结论

NKJY通过多靶点（AKT1/ESR1等）、多通路（抗氧化、抗炎、雌激素信号）调控“神经-生殖-血管”网络，以黄芩素、槲皮素等多成分协同改善焦虑行为、性激素紊乱及组织病理变化。

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

Keywords

references

刘雨昕 , 王国华 , 翟双庆 . 基于五神脏理论从脾胃辨治围绝经期情志疾病 [J ] . 北京中医药 , 2022 , 41 ( 9 ): 1007 - 1010 .

吴怡 , 葛梦迪 , 曹雯雯 , 等 . 围绝经期焦虑情绪的中西医发病机制与针刺治疗机制研究进展 [J ] . 河北中医 , 2023 , 45 ( 4 ): 695 - 698,704 .

张绍芬 , 包蕾 . 绝经期健康管理策略 [J ] . 实用妇产科杂志 , 2015 , 31 ( 5 ): 333 - 334 .

WANG X , ZHAO G , DI J , et al . Prevalence and risk factors for depressive and anxiety symptoms in middle-aged Chinese women:a community-based cross-sectional study [J ] . BMC Womens Health , 2022 , 22 ( 1 ): 319 .

吴静 , 王锦渝 . 心理护理对更年期焦虑症患者各项评分及生活质量的研究 [J ] . 检验医学与临床 , 2017 , 14 ( 14 ): 2134 - 2136 .

何于琼 , 蔡红霞 , 刘爱玲 . 围绝经期焦虑症研究进展 [J ] . 新疆中医药 , 2021 , 39 ( 1 ): 122 - 124 .

李奇 . 益肾疏肝汤改善乳腺癌内分泌治疗后类围绝经期综合征的疗效观察 [D ] . 北京 : 中国中医科学院 , 2019 .

潘琦 , 任菁菁 . 围绝经期血管舒缩症状治疗方法的研究进展 [J ] . 中华全科医学 , 2023 , 21 ( 9 ): 1566 - 1570 .

张欣 , 高珊 , 王运贤 , 等 . 柴胡桂枝汤加减对围绝经期综合征血管舒缩功能失调血清FSH、LH、E2水平和子宫内膜厚度影响 [J ] . 中华中医药学刊 , 2019 , 37 ( 12 ): 3010 - 3012 .

《中成药治疗优势病种临床应用指南》标准化项目组 . 中成药治疗更年期综合征临床应用指南(2020年) [J ] . 中国中西医结合杂志 , 2021 , 41 ( 4 ): 418 - 426 .

冯建超 , 郗川月 , 贾星星 , 等 . 李浩从肝论治围绝经期综合征临证思路 [J ] . 北京中医药 , 2016 , 35 ( 1 ): 52 - 54 .

王希元 . 柴胡加龙骨牡蛎汤合甘麦大枣汤加减治疗围绝经期综合征的临床研究 [D ] . 北京 : 北京中医药大学 , 2022 .

刘念 , 李吉磊 , 李丹艳 , 等 . 基于网络药理学和动物实验探讨健脾疏肝固本方治疗腹泻型肠易激综合征的作用机制 [J ] . 北京中医药 , 2024 , 43 ( 5 ): 460 - 468 .

苗明三 , 田硕 , 辛卫云 , 等 . 围绝经期综合征动物模型制备规范(草案) [J ] . 中华中医药杂志 , 2018 , 33 ( 3 ): 996 - 1000 .

MASOUDI M , GOODARZI M , RAHMANI MA , et al . Vitamin C improved anxiety and depression like behavior induced by chronic unpredictable mild stress in adolescent rats by influencing on oxidative stress balance,neurotransmitter systems,and inflammatory response [J ] . Nutr Neurosci , 2025 , 28 ( 4 ): 503 - 512 .

HSIN KY , GHOSH S , KITANO H . Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology [J ] . PLoS One , 2013 , 8 ( 12 ): e83922 .

李艳明 , 马秀兰 , 黄仕琦 , 等 . 基于网络药理学和实验验证探讨大补肝汤治疗广泛性焦虑症的作用机制 [J ] . 中国中药杂志 , 2024 , 49 ( 12 ): 3373 - 3384 .

牟艳卉 , 陈昭桂 , 姚光 , 等 . 针刺通过活性氧/c-Jun氨基末端激酶/p53通路对创伤后应激障碍大鼠模型海马神经元凋亡的影响机制 [J ] . 实用临床医药杂志 , 2025 , 29 ( 1 ): 44 - 49,72 .

李俊英 , 武静 , 王睿 . 柚皮素对围绝经期大鼠免疫及内分泌功能的影响及分子机制 [J ] . 基因组学与应用生物学 , 2019 , 38 ( 6 ): 2884 - 2888 .

LIU Q , WEI F , WANG J , et al . Molecular mechanisms regulating natural menopause in the female ovary:a study based on transcriptomic data [J ] . Front Endocrinol (Lausanne) , 2023 , 14 : 1004245 .

CHOTTEKALAPANDA RU , KALIK S , GRESACK J , et al . AP-1 controls the p11-dependent antidepressant response [J ] . Mol Psychiatry , 2020 , 25 ( 7 ): 1364 - 1381 .

GARDINI ES , FIACCO S , MERNONE L , et al . Sleep and methylation of estrogen receptor genes,ESR1 and GPER,in healthy middle-aged and older women:findings from the women 40+ healthy aging study [J ] . Nat Sci Sleep , 2020 , 12 : 525 - 536 .

HAN YK , KIM H , SHIN H , et al . Characterization of anti-inflammatory and antioxidant constituents from scutellaria baicalensis using LC-MS coupled with a bioassay method [J ] . Molecules , 2020 , 25 ( 16 ): 3617 .

LIAU PR , WU MS , LEE CK . Inhibitory Effects of scutellaria baicalensis root extract on linoleic acid hydroperoxide-induced lung mitochondrial lipid peroxidation and antioxidant activities [J ] . Molecules , 2019 , 24 ( 11 ): 2413 .

宋丽，王跃，田飞，等 . 黄芩素通过抑制氧化应激与凋亡改善小鼠心肌重构的作用研究 [J ] . 湖北民族大学学报(医学版) , 2022 , 39 ( 3 ): 1 - 7 .

张倩 , 李惠香 , 刘攀 , 等 . 黄芩素的体外抗炎及抗氧化活性研究 [J ] . 烟台大学学报(自然科学与工程版) , 2018 , 31 ( 3 ): 232 - 238 .

黄廷轩 , 郭姗姗 , 赵荣华 , 等 . 甘露消毒丹调控PI3K/Akt信号通路干预甲型流感病毒感染的作用机制 [J ] . 北京中医药 , 2024 , 43 ( 8 ): 871 - 879 .

SONG Q , PENG S , ZHU X . Baicalein protects against MPP+/MPTP-induced neurotoxicity by ameliorating oxidative stress in SH-SY5Y cells and mouse model of Parkinson's disease [J ] . Neurotoxicology , 2021 , 87 : 188 - 194 .

姚倩 . 清心滋肾方治疗围绝经期综合征心肾不交型的临床研究及网络药理学分析 [D ] . 南京 : 南京中医药大学 , 2022 .

BAEYENS N , BANDYOPADHYAY C , COON BG , et al . Endothelial fluid shear stress sensing in vascular health and disease [J ] . J Clin Invest , 2016 , 126 ( 3 ): 821 - 828 .

罗煜 , 吴嘉思 , 朱正文 , 等 . 盐酸巴马汀抑制NF-κB/p38 MAPK信号通路及NLRP3炎症小体抗炎机制研究 [J ] . 中药新药与临床药理 , 2020 , 31 ( 7 ): 762 - 768 .

韦春昕 , 胡亦明 , 黄仕琦 , 等 . 基于p38 MAPK/NF-κB信号通路探讨柴胡加龙骨牡蛎汤干预广泛性焦虑模型大鼠的作用机制 [J ] . 中国实验方剂学杂志 , 2024 , 30 ( 4 ): 114 - 123 .

武春艳 , 刘录山 , 姜志胜 . 血流剪切应力信号转导与动脉粥样硬化的关系 [J ] . 东南大学学报(医学版) , 2009 , 28 ( 5 ): 446 - 450 .

CHEN J , LI H , YANG C , et al . citrus naringenin increases neuron survival in optic nerve crush injury model by inhibiting JNK-JUN pathway [J ] . Int J Mol Sci , 2021 , 23 ( 1 ): 385 .

甄艳杰 , 刘靓靓 , 赵雨薇 , 等 . 槲皮素对大鼠皮层神经元的雌激素样作用研究 [J ] . 中国药理学通报 , 2020 , 36 ( 12 ): 1744 - 1749 .

杨颖 , 王芸芸 , 蒋琦辰 . 槲皮素药理作用的研究进展 [J ] . 特种经济动植物 , 2020 , 23 ( 5 ): 24 - 28 .

王叶情 , 王宇红 , 邹蔓姝 , 等 . 槲皮素及其糖苷衍生物抗抑郁作用及其机制的研究进展 [J ] . 中草药 , 2022 , 53 ( 5 ): 1548 - 1557 .

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Efficacy and mechanisms of Ningkun Jieyu Decoction in the treatment of perimenopausal anxiety based on network pharmacology, molecular docking, and animal experiments

DOI：10.16025/j.1674-1307.2025.11.009

摘要

Abstract

关键词

Keywords

references