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1.广州中医药大学 第一临床医学院,广州 510405;
2.广州中医药大学 第一附属医院,广州 510405;
3.南方医科大学 中医药学院,广州 510405;
4.暨南大学 中医学院,广州 510405
王强,在读博士,从事中医药防治风湿病研究,E-mail:wangqiang5250@163.com
林昌松,博士生导师,从事中医药防治风湿病研究,Tel:020-36598915,E-mail:linchs999@163.com
收稿日期:2019-04-14,
网络出版日期:2019-09-05,
纸质出版日期:2019-12-20
移动端阅览
王强, 刘敏莹, 韩隆胤, 等. 基于网络药理学探讨断藤益母汤治疗类风湿关节炎的作用机制[J]. 中国实验方剂学杂志, 2019,25(24):150-158.
Qiang WANG, Min-ying LIU, Long-yin HAN, et al. Mechanism of Duanteng Yimutang in Treating Rheumatoid Arthritis Based on Network Pharmacology Approach[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(24): 150-158.
王强, 刘敏莹, 韩隆胤, 等. 基于网络药理学探讨断藤益母汤治疗类风湿关节炎的作用机制[J]. 中国实验方剂学杂志, 2019,25(24):150-158. DOI: 10.13422/j.cnki.syfjx.20192404.
Qiang WANG, Min-ying LIU, Long-yin HAN, et al. Mechanism of Duanteng Yimutang in Treating Rheumatoid Arthritis Based on Network Pharmacology Approach[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(24): 150-158. DOI: 10.13422/j.cnki.syfjx.20192404.
目的:
2
断藤益母汤在类风湿关节炎中疗效显著,但其成分复杂,作用机制不明。使用网络药理学方法对断藤益母汤的分子机制进行研究,寻找断藤益母汤的有效成分、治疗靶标和信号通路具有一定价值。
方法:
2
根据药代动力学参数在中药系统药理学数据库及分析平台(TCMSP)和中医综合数据库(TCMID)筛选药物成分。在Drugbank数据库和TTD数据库挖掘药物和疾病靶标,使用可视化网络药理学Cytoscap工具构建药物-靶点-通路网络,探讨断藤益母汤中成分的作用机制。
结果:
2
发现断藤益母汤的11个有效成分可能靶向42个类风湿关节炎相关靶点,如白细胞介素-1(IL-1),白细胞介素-6(IL-6),肿瘤坏死因子(TNF),环氧化酶2(COX2),基质金属蛋白酶-1(MMP-1),基质金属蛋白酶-3(MMP-3),诱导型一氧化氮合酶(NOS
2
)等。参与了包括肿瘤坏死因子(TNF)信号通路,白细胞介素-17(IL-17)通路,辅助性T细胞17(Th17)分化通路,风湿关节炎通路、核转录因子-
κ
B (NF-
κ
B)通路、破骨细胞分化通路、卵巢类固醇生成通路等多条通路。
结论:
2
断藤益母汤可能主要通过多条炎症相关信号通路对炎性细胞因子进行调控,从而对类风湿关节炎起到抗炎和免疫调控作用。
Objective:
2
Duanteng Yimutang(DTYMT) has a significant effect in treating rheumatoid arthritis
but its composition is complex and its mechanism is not clear. It is worthwhile to use network pharmacology approach to find active components
therapeutic targets and signal pathways of DTYMT.
Method:
2
The drug composition was selected according to the pharmacokinetic parameters in the pharmacology database
the analysis platform (TCMSP) and the TCM integrated database (TCMID) of the Traditional Chinese Medicine System. The drug and disease targets were excavated in the Drugbank database and the Therapeutic Target Database (TTD)
and the drug-target-pathway network was constructed by network pharmacology tool Cytoscap
in order to explore the mechanism of the action of the components in the DTYMT.
Result:
2
It was found that 11 effective components of DTYMT could target 42 proteins in rheumatoid arthritis
such as interleukin-1 (IL-1)
interleukin-6 (IL-6)
tumor necrosis factor (TNF)
cyclooxygenase-2 (COX2)
matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3)
and inducible nitric oxide synthase (NOS2). Various pathways
including tumor necrosis factor (TNF) signaling pathway
interleukin-17 (IL-17) pathway
helper T cell 17 (Th17) differentiation pathway
rheumatic arthritis pathway
nuclear factor
κ
B (NF-
κ
B) pathway
osteoclast differentiation pathway
and ovarian steroid production pathway
were involved.
Conclusion:
2
DTYMT may be used to regulate inflammatory cytokines mainly through multiple inflammatory-related signal pathways
so as to play anti-inflammatory and immunoregulatory roles in the treatment of rheumatoid arthritis.
Smolen J S , Aletaha D , McInnes I B . Rheumatoid arthritis [J]. Lancet , 2016 , 388 ( 10055 ): 2023 - 2038 .
Wojdasiewicz P , Poniatowski L A , Szukiewicz D . The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis [J]. Mediators Inflamm , 2014 , 2014 : 561459 .
Talotta R , Atzeni F , Batticciotto A , et al . Biological agents in rheumatoid arthritis: a cross-link between immune tolerance and immune surveillance [J]. Curr Rheumatol Rev , 2018 , 14 ( 2 ): 131 - 139 .
Carrera C G , Dapavo P , Malagoli P , et al . PACE study: real-life psoriasis area and severity index (PASI) 100 response with biological agents in moderate-severe psoriasis [J]. J Dermatolog Treat , 2018 , 29 ( 5 ): 481 - 486 .
林昌松 , 梁江 , 刘风震 , 等 . 断藤益母汤治疗类风湿关节炎的临床疗效观察 [J]. 广州中医药大学学报 , 2012 , 29 ( 6 ): 632 - 637 .
蔡叙东 , 林昌松 , 潘东梅 , 等 . 断藤益母汤对破骨细胞活性及Wnt信号通路的影响研究 [J]. 中华中医药学刊 , 2018 , 36 ( 10 ): 2332 - 2335 .
蔡叙东 , 林昌松 , 潘东梅 , 等 . 断藤益母汤对破骨细胞RANKL信号通路及MMP-9的影响 [J]. 中国实验方剂学杂志 , 2018 , 24 ( 12 ): 68 - 73 .
潘东梅 , 王强 , 蔡叙东 , 等 . 断藤益母汤抑制PI3K/AKT通路诱导类风湿关节炎成纤维样滑膜细胞凋亡 [J]. 中华中医药杂志 , 2018 , 33 ( 5 ): 2051 - 2055 .
Boezio B , Audouze K , Ducrot P , et al . Network-based approaches in pharmacology [J]. Mol Inform , 2017 , 36 ( 10 ): 114 - 119 .
LI S , ZHANG B . Traditional Chinese medicine network pharmacology: theory, methodology and application [J]. Chin J Nat Med , 2013 , 11 ( 2 ): 110 - 120 .
许海玉 , 刘振明 , 付岩 , 等 . 中药整合药理学计算平台的开发与应用 [J]. 中国中药杂志 , 2017 , 42 ( 18 ): 3633 - 3638 .
王萍 , 唐仕欢 , 苏瑾 , 等 . 基于整合药理学的中药现代研究进展 [J]. 中国中药杂志 , 2018 , 43 ( 7 ): 1297 - 1302 .
Wishart D S , Feunang Y D , Guo A C , et al . DrugBank 5.0: a major update to the DrugBank database for 2018 [J]. Nucleic Acids Res , 2018 , 46 ( D1 ): D1074 - D1082 .
CHEN X , JI Z L , CHEN Y Z . TTD: Therapeutic target database [J]. Nucleic Acids Res , 2002 , 30 ( 1 ): 412 - 415 .
GUAN L , YANG H , CAI Y , et al . ADMET-score-a comprehensive scoring function for evaluation of chemical drug-likeness [J]. Medchemcomm , 2019 , 10 ( 1 ): 148 - 157 .
RU J , LI P , WANG J , et al . TCMSP: a database of systems pharmacology for drug discovery from herbal medicines [J]. J Cheminform , 2014 , 6 ( 1 ): 13 .
HUANG L , XIE D , YU Y , et al . TCMID 2.0: a comprehensive resource for TCM [J]. Nucleic Acids Res , 2018 , 46 ( D1 ): D1117 - D1120 .
Shannon P , Markiel A , Ozier O , et al . Cytoscape: a software environment for integrated models of biomolecular interaction networks [J]. Genome Res , 2003 , 13 ( 11 ): 2498 - 2504 .
LIN J S , LAI E M . Protein-protein interactions: co-immunoprecipitation [J]. Methods Mol Biol , 2017 , 1615 : 211 - 219 .
Smits A H , Vermeulen M . Characterizing protein-protein interactions using mass spectrometry: challenges and opportunities [J]. Trends Biotechnol , 2016 , 34 ( 10 ): 825 - 834 .
Szklarczyk D , Morris J H , Cook H , et al . The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible [J]. Nucleic Acids Res , 2017 , 45 ( D1 ): D362 - D368 .
黄海滨 , 杨路明 , 王建新 , 等 . 基于网络拓扑的生物网络关键节点识别研究进展 [J]. 数学的实践与认识 , 2011 , 41 ( 7 ): 114 - 125 .
Alam J , Jantan I , Bukhari S . Rheumatoid arthritis: recent advances on its etiology, role of cytokines and pharmacotherapy [J]. Biomed Pharmacother , 2017 , 92 : 615 - 633 .
Sheppard M , Laskou F , Stapleton P P , et al . Tocilizumab (Actemra) [J]. Hum Vaccin Immunother , 2017 , 13 ( 9 ): 1972 - 1988 .
Kristensen M , Chu C Q , Eedy D J , et al . Localization of tumour necrosis factor-alpha (TNF-alpha) and its receptors in normal and psoriatic skin: epidermal cells express the 55-kD but not the 75-kD TNF receptor [J]. Clin Exp Immunol , 1993 , 94 ( 2 ): 354 - 362 .
Murdaca G , Negrini S , Magnani O , et al . Update upon efficacy and safety of etanercept for the treatment of spondyloarthritis and juvenile idiopathic arthritis [J]. Mod Rheumatol , 2018 , 28 ( 3 ): 417 - 431 .
Fidahic M , Jelicic K A , Radic M , et al . Celecoxib for rheumatoid arthritis [J]. Cochrane Database Syst Rev , 2017 , 6 : D12095 .
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