关键词: Inflammation Mechanism Multiple targets Network pharmacology Phellodendrine

Mesh : Humans Cyclooxygenase 2 Network Pharmacology Inflammation / drug therapy Quinolizines / pharmacology

来  源:   DOI:10.7717/peerj.13852   PDF(Pubmed)

Abstract:
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.
摘要:
黄柏,黄柏的特征和重要活性成分之一,已被证明具有抗炎作用。然而,黄柏碱对炎症的潜在机制仍不清楚。
在这项研究中,通过网络药理学和实验验证,探讨黄柏碱对炎症的作用机制。
使用PubChem和SwissADME数据库评估黄柏碱的药物相似性和其他特征。用多个数据库分析黄柏碱治疗炎症的靶标。其他广泛的分析,包括蛋白质-蛋白质相互作用,基因本体论,和京都百科全书的基因和基因组途径富集与STRING数据库完成,Cytoscape软件,和DAVID数据库。此外,黄柏碱的抗炎作用在RAW264.7中得到证实。
网络药理学结果表明黄柏碱具有药物潜力。黄柏直接作用于12个目标,包括PTGS1,PTGS2,HTR1A,和PIK3CA,然后调节cAMP,雌激素,TNF,血清素能突触,等信号通路发挥抗炎作用。实验结果表明,黄柏碱与LPS组相比,在24h内降低IL-6水平,改变PTGS1、PTGS2、HSP90ab1、AKT1、HTR1A、PI3CA,F10
我们的研究初步揭示了黄柏碱对炎症的治疗机制,具有多个靶点和途径。黄柏碱可能是与cAMP和TNF信号通路相关的炎症相关疾病的潜在治疗方法。
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