Utilizing network pharmacology and experimental validation to investigate the underlying mechanism of phellodendrine on inflammation.
Utilizing network pharmacology and experimental validation to investigate the underlying mechanism of phellodendrine on inflammation.
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作者：
Hu L;Wang J;Wu N;Zhao X;Cai D
广木香碱是广木香的特征性活性成分之一，具有抗炎作用。然而，山茱萸碱对炎症的潜在机制在很大程度上仍不清楚。本研究采用网络药理学和实验验证相结合的方法，探讨山茱萸碱抗炎作用的机制。PubChem和SwissADME数据库用于评价杜鹃碱的药物相似性和其他特征。用多个数据库分析了野牡丹碱治疗炎症的靶点。其他广泛的分析，包括蛋白质-蛋白质相互作用，基因本体论，和京都基因百科全书和基因组途径富集完成与STRING数据库，Cytoscape软件，和大卫数据库。此外，在RAW264.7中证实了杜鹃碱的抗炎作用。网络药理学结果表明黄柏碱具有药物潜力。雷公藤甲素直接作用于PTGS 1、PTGS 2、HTR 1A、PIK 3CA等12个靶点，通过调节cAMP、雌激素、TNF、β-肾上腺素能突触等信号通路发挥抗炎作用。结果表明，与LPS组相比，雷公藤甲素可降低IL-6水平，并改变PTGS 1、PTGS 2、HSP 90 ab 1、AKT 1、HTR 1A、PI 3CA和F10的mRNA表达。本研究初步揭示了山茱萸碱治疗炎症的多靶点、多途径机制。山茱萸碱可能是一种潜在的治疗与cAMP和TNF信号通路相关的炎症相关疾病的药物。
Phellodendrine, one of the characteristic and important active components of Cortex phellodendri, has been proven to show anti-inflammatory effects. However, the underlying mechanism of phellodendrine on inflammation remains largely unclear. In this study, network pharmacology and experimental validation were used to explore the underlying mechanism of phellodendrine on inflammation. PubChem and SwissADME database were used to evaluate the drug-likeness and other characteristics of phellodendrine. The targets of phellodendrine for the treatment of inflammation were analyzed with multiple databases. Other extensive analyses including protein–protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were accomplished with the STRING database, Cytoscape software, and DAVID database. Moreover, the effect of phellodendrine on anti-inflammation was proven in RAW264.7. The network pharmacology results indicated that phellodendrine had drug potential. Phellodendrine acted directly on 12 targets, including PTGS1, PTGS2, HTR1A, and PIK3CA, and then regulated cAMP, estrogen, TNF, serotonergic synapse, and other signaling pathways to exert anti-inflammatory effects. The experimental results showed that phellodendrine reduced the levels of IL-6 compared with the LPS group in 24 h and changed the mRNA expression of PTGS1, PTGS2, HSP90ab1, AKT1, HTR1A, PI3CA, and F10. Our research preliminarily uncovered the therapeutic mechanisms of phellodendrine on inflammation with multiple targets and pathways. Phellodendrine may be a potential treatment for inflammation-related diseases related to the cAMP and TNF signaling pathways.
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影响因子：
4.6
作者：
Daina A;Michielin O;Zoete V
通讯作者：
Zoete V
影响因子：
32.4
作者：
Rohm TV;Meier DT;Olefsky JM;Donath MY
通讯作者：
Donath MY
影响因子：
5
作者：
Garcia-Mediavilla, Victoria;Crespo, Irene;Gonzalez-Gallego, Javier
通讯作者：
Gonzalez-Gallego, Javier
DOI：
10.1126/science.1226625
发表时间：
2012-11-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Doronin K;Flatt JW;Di Paolo NC;Khare R;Kalyuzhniy O;Acchione M;Sumida JP;Ohto U;Shimizu T;Akashi-Takamura S;Miyake K;MacDonald JW;Bammler TK;Beyer RP;Farin FM;Stewart PL;Shayakhmetov DM
通讯作者：
Shayakhmetov DM
影响因子：
13.8
作者：
Cirino, G;Napoli, C;Cicala, C
通讯作者：
Cicala, C