Wang Xin-Meng, Tang Xiao-Han, Li Ying-Yao, Pu Xue-Xue, Zhou Yan
Chengdu Institute of Biology,Chinese Academy of Sciences Chengdu 610041,China University of Chinese Academy of Sciences Beijing 100049,China.
Kunming Institute of Botany,Chinese Academy of Sciences Kunming 650201,China.
Zhongguo Zhong Yao Za Zhi. 2021 Jul;46(14):3625-3632. doi: 10.19540/j.cnki.cjcmm.20210312.201.
In this paper,metabolomics and network pharmacology were used to investigate the bioactive components of Harrisonia perforata and their possible mechanisms of action. Metabolites in the flowers,fruits,branches,leaves and stalks of H. perforata were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Meanwhile,multiple statistical analysis methods including principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA)were applied to screen and identify differential compounds. With metabolomics method,9 differential compounds were preliminarily identified from leaves and other non-traditional medicinal parts. Subsequently,these compounds were explored by using network pharmacology. With gastrointestinal absorption and drug-likeness as limiting conditions,they were imported into the Swiss ADME,from which 7 compounds with potential medicinal activity were obtained. Then,their targets were predicted by PharmMapper,with Human Protein Targets Only and Normalized Fit Score>0. 9 set as limiting conditions,and 60 standardized potential targets were identified with Uniprot. KEGG( Kyoto encyclopedia of genes and genomes) pathway data was obtained using metascape and the " potential active ingredients-target-pathway" network was constructed with Cytoscape 3. 7. 2. The enrichment analysis of KEGG demonstrated that the 60 targets were enriched in 78 signaling pathways( min overlap: 3,P value cutoff: 0. 01,min enrichment: 1. 5),many of which are related to anti-bacteria,anti-inflammation and anti-virus,such as IL-17 signaling pathway,RIG-I-like receptor signaling pathway and NOD-like receptor signaling pathway. Finally,depending on the clinical activity of H. perforata,the relevant signaling pathways were analyzed through experimental data and literature. Dehydroconiferyl alcohol was reported to have the anti-inflammatory effect and perforamone D to possess the antimycobacterial activity. The KEGG pathway enrichment analysis showed that dehydroconiferyl alcohol could act on the Alzheimer's disease( AD) signaling pathway by targeting CDK5 R1 and BACE1. ACh E inhibitor is the most promising drug to treat AD,while dehydroconiferyl alcohol has been proved to inhibit ACh E according to literature. The experimental results revealed that the extract of leaves of H. perforata can effectively inhibit the growth of Staphylococcus aureus. These are consistent with the enrichment analysis results of KEGG. This study explored the bioactive components and pharmacodynamics of the leaves of the H. perforata,laying a theoretical foundation for its in-depth development and rational application.
在本文中，运用代谢组学和网络药理学来研究刺蒴麻的生物活性成分及其可能的作用机制。采用超高效液相色谱 - 四极杆 - 飞行时间质谱法分析刺蒴麻的花、果实、枝条、叶片和茎中的代谢物。同时，应用包括主成分分析（PCA）和正交偏最小二乘法判别分析（OPLS - DA）在内的多种统计分析方法来筛选和鉴定差异化合物。通过代谢组学方法，从叶片和其他非传统药用部位初步鉴定出9种差异化合物。随后，利用网络药理学对这些化合物进行探究。以胃肠道吸收和类药性为限制条件，将它们导入瑞士ADME系统，从中获得7种具有潜在药用活性的化合物。然后，通过PharmMapper预测它们的靶点，设定仅以人类蛋白质靶点和标准化拟合分数>0.9为限制条件，并通过Uniprot鉴定出60个标准化的潜在靶点。使用metascape获取KEGG（京都基因与基因组百科全书）通路数据，并使用Cytoscape 3.7.2构建“潜在活性成分 - 靶点 - 通路”网络。KEGG的富集分析表明，这60个靶点富集在78条信号通路中（最小重叠：3，P值截止：0.01，最小富集：1.5），其中许多与抗菌、抗炎和抗病毒有关，如IL - 17信号通路、RIG - I样受体信号通路和NOD样受体信号通路。最后，根据刺蒴麻的临床活性，通过实验数据和文献对相关信号通路进行分析。据报道，脱氢松柏醇具有抗炎作用，穿孔酮D具有抗分枝杆菌活性。KEGG通路富集分析表明，脱氢松柏醇可通过靶向CDK5 R1和BACE1作用于阿尔茨海默病（AD）信号通路。乙酰胆碱酯酶抑制剂是治疗AD最有前景的药物，而根据文献，脱氢松柏醇已被证明可抑制乙酰胆碱酯酶。实验结果表明，刺蒴麻叶片提取物能有效抑制金黄色葡萄球菌的生长。这些与KEGG的富集分析结果一致。本研究探究了刺蒴麻叶片的生物活性成分和药效学，为其深入开发和合理应用奠定了理论基础。
