基于网络药理学探讨圣草酚对树突状细胞成熟的影响及分子机制

刘晓颖; 阿力木·艾麦尔; 樊栩; 王为兰; 王新绘; 李金耀

doi:10.13568/j.cnki.651094.651316.2021.04.10.0002

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基于网络药理学探讨圣草酚对树突状细胞成熟的影响及分子机制

更新时间：2026-01-21

- 基于网络药理学探讨圣草酚对树突状细胞成熟的影响及分子机制
- Journal of Xinjiang University (Natural Science Edition in Chinese and English) Vol. 39, Issue 3, Pages: 331-339(2022)
- 作者机构：
  
  1. 新疆大学生命科学与技术学院新疆生物资源基因工程重点实验室
  2. 新疆大学资源与环境科学学院
- 作者简介：
- 基金信息：
- DOI：10.13568/j.cnki.651094.651316.2021.04.10.0002
  CLC： R285
- Published：2022
- 稿件说明：
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[1]刘晓颖,阿力木·艾麦尔,樊栩,等.基于网络药理学探讨圣草酚对树突状细胞成熟的影响及分子机制[J].新疆大学学报(自然科学版)(中英文),2022,39(03):331-339+349.
[1]刘晓颖,阿力木·艾麦尔,樊栩,等.基于网络药理学探讨圣草酚对树突状细胞成熟的影响及分子机制[J].新疆大学学报(自然科学版)(中英文),2022,39(03):331-339+349. DOI： 10.13568/j.cnki.651094.651316.2021.04.10.0002.

DOI：10.13568/j.cnki.651094.651316.2021.04.10.0002.

摘要

为探讨圣草酚对树突状细胞（dendritic cell

DC）成熟影响及其分子作用机制，基于网络药理学，通过多个数据平台获得圣草酚对DC、免疫抑制及炎症反应的相关靶点．采用Cytoscape 3.6.1软件构建活性成分潜在靶点网络，并利用String平台构建蛋白相互作用（PPI）网络．利用Metascape平台进行GO和KEGG富集分析，利用Autodock Vina软件进行分子对接．不同浓度（210μM、280μM和350μM）圣草酚单独或与细菌脂多糖（LPS）联用处理DC，流式细胞术检测细胞表面分子表达，ELISA检测细胞因子表达，Western blot检测基质金属蛋白MMP9的表达．获得圣草酚作用靶点96个，DC相关72个，免疫抑制相关14个，炎症反应相关48个，共有核心靶点包括AKT1、SRC、MMP9及MMP2等，主要关联氧化应激及细胞迁移等生物学过程，涉及癌症的信号通路、Ras信号通路、表皮生长因子受体酪氨酸激酶抑制剂抗性、c型凝集素受体信号通路、肿瘤坏死因子信号通路等信号通路．分子对接显示，圣草酚与MMP9具有更强的结合作用．体外实验显示，圣草酚能显著抑制LPS诱导的DC表面分子CD40(P<0.01)和CD86(P<0.001)、细胞因子TNF-α(P<0.001)及IL-6(P<0.001)以及基质金属蛋白酶MMP9(P<0.01)的表达．圣草酚通过抑制DC表面共刺激分子CD40和CD86、促炎细胞因子TNF-α和IL-6表达及MMP9等抑制DC成熟及迁移．

Abstract

To investigate the effect of eriodictyol on dendritic cell(DC) maturation and the molecular mechanism

based on network pharmacology

the related targets for DC

immunosuppression and inflammatory response were obtained through multiple data platforms. Cytoscape 3.6.1 software was used to construct the active componentpotential target network

and the String was used to construct the protein interaction(PPI) network. GO and KEGG enrichment analysis were performed using Metascape

and the molecular docking was performed using Autodock Vina software. DCs were treated with different concentrations(210 μM

280 μM and 350 μM) of eriodictyolin the absence or presence of lipopolysaccharides(LPS). The expression of cell surface molecules was detected by flow cytometry

cytokine secretion was detected by ELISA

and matrix metalloprotein MMP9 expression was detected by Western blot. 96 related targets were screened

72 of them related to DC

14 of them related to immunosuppression

and 48 of them related to inflammatory response. The core targets included AKT1

SRC

MMP9 and MMP2

etc.

which were involved in biological processes such as the oxidative stress and the cell migration and signaling pathways including pathways in cancer

Ras signaling pathway

EGFR tyrosine kinase inhibitor resistance

c-type lectin receptor signaling pathway and TNF signaling pathway. The molecular docking showed that eriodictyol had stronger binding effect with MMP9. In vitro

eriodictyol significantly suppressed LPS-induced DC maturation characterized by the decreased levels of CD40(P <0.01)

CD86(P <0.001)

TNF-α(P <0.001)

IL-6(P <0.001) and MMP9(P <0.01). Eriodictyol inhibited the maturation and migration of DC through co-stimulatory molecules CD40 and CD86

pro-inflammatory cytokines TNF-α and IL-6

and MMP9.

关键词

Keywords

references

LI J,WANG X,WANG W,et al.Pleurotus ferulae water extract enhances the maturation and function of murine bone marrowderived dendritic cells through TLR4 signaling pathway[J].Vaccine,2015,33(16):1923-1933.

BOLTJES A,WIJK F V.Human dendritic cell functional specialization in steady-state and infammation[J].Frontiers in Immunology,2014,5:131.

AZEGULI H,LI J Y,ZHOU F F,et al.Capparis spinosa fruit ethanol extracts exert different effects on the maturation of dendritic cells[J].Molecules,2017,22(1):97.

LIN M K,YU Y L,CHEN K C,et al.Kaempferol from Semen cuscutae attenuates the immune function of dendritic cells[J].Immunobiology,2011,216(10):1103-1109.

ZHAO Y,LI J,YU K,et al.Sinomenine inhibits maturation of monocyte-derived dendritic cells through blocking activation of NF-kappa B[J].International Immunopharmacology,2007,7(5):637-645.

LIU L,LIAO P,WANG B,et al.Oral administration of baicalin and geniposide induces regression of atherosclerosis via inhibiting dendritic cells in Apo E-knockout mice[J].International Immunopharmacology,2014,20(1):197-204.

CHEN C A,LIU C K,HSU M L,et al.Daphnoretin modulates differentiation and maturation of human dendritic cells through down-regulation of c-Jun N-terminal kinase[J].International Immunopharmacology,2017,51:25-30.

ZHANG R Z,YU S J,BAI H,et al.TCM-mesh:the database and analytical system for network pharmacology analysis for TCMpreparations[J].Scientific Reports,2017,7(1):2821.

WANG Z,LAN Y,CHEN M,et al.Eriodictyol,not its glucuronide metabolites,attenuates acetaminopheninduced hepatotoxicity[J].Molecular Pharmaceutics,2017,14(9):2937-2951.

ISLAM A,ISLAM S,RAHMAN K,et al.The pharmacological and biological roles of eriodictyol[J].Archives of Pharmacal Research,2020,43(6):582-592.

WANG Y S,CHEN Y,CHEN Y,et al.Eriodictyol inhibits IL-1β-induced infammatory response in human osteoarthritis chondrocytes[J].Biomedicine&Pharmacotherapy,2018,107:1128-1134.

WANG R,SHEN L.Effect of eriodictyol on Nrf2/HO-1 pathway in mice experimental colitis[J].Chinese Journal of Immunology,2020,36(8):928-932.

WANG X,DENG R,DONG J,et al.Eriodictyol ameliorates lipopolysaccharide-induced acute lung injury by suppressing the infammatory COX-2/NLRP3/NF-κB pathway in mice[J].Journal of Biochemical and Molecular Toxicology,2020,34(3):e22434.

OSMAN M,TORTORELLA M,LONDEI M,et al.Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases define the migratory characteristics of human monocyte-derived dendritic cells[J].Immunology,2002,105:73-82.

ZOZULYA A L,REINKE E,BAIU D C,et al.Dendritic cell transmigration through brain microvessel endothelium is regulated by MIP-1αchemokine and matrix metalloproteinases[J].The Journal of Immunology,2007,178(1):520-529.

SOUSA C R E.Dendritic cells in a mature age[J].Nature Reviews Immunology,2006,6(6):476-483.

YU S M,KIM S J.Withaferin A-caused production of intracellular reactive oxygen species modulates apoptosis via PI3K/Akt and JNKinase in rabbit articular chondrocytes[J].Journal of Korean Medical Science,2014,29(8):1042-1053.

SUGIMORI K,MATSUI K,MOTOMURA H,et al.BMP-2 prevents apoptosis of the N1511 chondrocytic cell line through PI3K/Akt-mediated NF-κB activation[J].Journal of Bone&Mineral Metabolism,2005,23(6):411-419.

LEE K N,SEO M C,BAE I H,et al.COMP-Ang1,a variant of angiopoietin1,inhibits serum-deprived apoptosis of mesenchymal cells via PI3K/Akt and mitogen-activated protein kinase pathways[J].Pharmacology,2010,86(5/6):327-335.

LI X,WANG Y.Cinnamaldehyde attenuates the progression of rheumatoid arthritis through down-regulation of PI3K/Akt signaling pathway[J].Infammation,2020,43(9746):1729-1741.

XIANG M,LIU T T,TAN W Y,et al.Effects of kinsenoside,a potential immunosuppressive drug for autoimmune hepatitis,on dendritic cells/CD8+T cells communication in mice[J].Hepatology,2016,64(6):2135-2150.

LIU Y C,YAN X N.Eriodictyol inhibits survival and infammatory responses and promotes apoptosis in rheumatoid arthritis fibroblast-like synoviocytes through AKT/FOXO1 signaling[J].Journal of Cellular Biochemistry,2019,120(9):14628-14635.

LIU J F,CHEN P C,CHANG T M,et al.Thrombospondin-2 stimulates MMP-9 production and promotes osteosarcoma metastasis via the PLC,PKC,c-Src and NF-κB activation[J].Journal of Cellular and Molecular Medicine,2020,24(21):12826-12839.

ALAMGEER,UMME H H,AMBEREN M U,et al.Phytochemicals targeting matrix metalloproteinases regulating tissue degradation in infammation and rheumatoid arthritis[J].Phytomedicine,2020,66:153134.

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