Feng Qun, Sun Cheng-Hong, Li Shi-Rong, Li Xiang-Zi, Xiao Min, Zhao Tao, Zhang Gui-Min
State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine Linyi 276006, China.
Center for New Drug Pharmacology, Lunan Pharmaceutical Group Co., Ltd. Linyi 273400, China.
Zhongguo Zhong Yao Za Zhi. 2022 Oct;47(20):5481-5487. doi: 10.19540/j.cnki.cjcmm.20220414.401.
The present study aimed to explore the regulatory targets and anti-inflammatory mechanism of Jingfang Mixture based on network pharmacology and animal tests. The active ingredients of Jingfang Mixture and the corresponding targets were screened out by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Inflammation-related targets were searched from GeneCards and DisGeNET, and the targets of active ingredients of Jingfang Mixture against inflammation were obtained. The protein-protein interaction(PPI) network was analyzed by STRING and plotted. Gene ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out based on DAVID. The results of network pharmacology showed 159 active ingredients and 276 targets of Jingfang Mixture and 664 inflammation-related targets were screened out, and 90 targets of active ingredients of Jingfang Mixture against inflammation were obtained. As revealed by the PPI network, protein kinase B1(AKT1), caspase-3(CASP3), interleukin-1β(IL1 B), prostaglandin-endoperoxide synthase 2(PTGS2), and tumor necrosis factor(TNF) might be the key proteins for the anti-inflammatory effect of Jingfang Mixture. KEGG enrichment analysis demonstrated the pathways involved TNF, nuclear factor-kappa B(NF-κB), and mitogen-activated protein kinase(MAPK). The anti-inflammatory effect of Jingfang Mixture was explored through the mouse model of urticaria. The results indicated that Jingfang Mixture could down-regulate the phosphorylation levels of p38 MAPK, extracellular regulated protein kinases(ERK1/2), and NF-κB. The present study revealed the anti-inflammatory effect of Jingfang Mixture with multi-component and multi-target characteristics, which is expected to provide a scientific basis and important support for further research, development, and application.
本研究旨在基于网络药理学和动物实验探索荆防合剂的调控靶点及抗炎机制。通过中药系统药理学数据库与分析平台（TCMSP）筛选出荆防合剂的活性成分及相应靶点。从GeneCards和DisGeNET中检索炎症相关靶点，得到荆防合剂活性成分的抗炎靶点。利用STRING分析并绘制蛋白质-蛋白质相互作用（PPI）网络。基于DAVID进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析。网络药理学结果显示，筛选出荆防合剂的159种活性成分和276个靶点以及664个炎症相关靶点，得到荆防合剂活性成分的90个抗炎靶点。PPI网络显示，蛋白激酶B1（AKT1）、半胱天冬酶-3（CASP3）、白细胞介素-1β（IL1 B）、前列腺素内过氧化物合酶2（PTGS2）和肿瘤坏死因子（TNF）可能是荆防合剂抗炎作用的关键蛋白。KEGG富集分析表明，涉及的通路有TNF、核因子-κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）。通过荨麻疹小鼠模型探究荆防合剂的抗炎作用。结果表明，荆防合剂可下调p38 MAPK、细胞外调节蛋白激酶（ERK1/2）和NF-κB的磷酸化水平。本研究揭示了荆防合剂具有多成分、多靶点的抗炎作用，有望为进一步的研究、开发和应用提供科学依据和重要支持。
