基于网络模块分析的降香黄酮类成分抗炎机制研究

Anti-inflammatory mechanism research of flavonoid compounds in Dalbergiae Odoriferae Lignum by module-based network analysis

黄酮类化合物作为降香主要活性成分之一,具有抗炎作用。该研究以具有抗炎活性的异甘草素、甘草素、柚皮素及紫铆花素黄酮类化合物为研究载体,通过数据库检索确定化合物的作用靶点,利用靶点的蛋白质相互作用信息构建降香黄酮类化合物作用的蛋白互作网络。采用分子复合物检测算法(MCODE)对网络进行模块分析,利用Cytoscape软件中的BinGO插件,从Gene Ontology获取数据,从而对识别出的模块进行功能注释,通过模块功能探讨阐释降香黄酮类化合物抗炎作用机制,结果显示其主要与抑制FOS,PTGS2表达、抑制IL-1β释放、抑制MAPK通路和Toll样受体通路有关。

Dalbergiae Odoriferae Lignum as a traditional Chinese medicine （TCM） has been widely used for promoting blood circu- lation and removing blood stasis. Flavonoid compounds are main chemical constituents of Dalbergiae Odoriferae Lignum, which exert anti-inflammatory property. However, the underlying anti-inflammatory mechanisms of flavonoid compounds are incompletely under- stood. It has been reported that isoliquiritigenin, liquiritigenin, naringenin and butein possess anti-inflammatory property. The purpose of this study is to illuminate the anti-inflammatory mechanism of flavonoid compounds based on the protein interaction network （PIN） analysis on molecular network level. 130 targets of the main medicinal ingredients of flavonoid compounds were gained though database retrieval. A protein interaction network of flavonoid compounds was constructed with 589 nodes and 216 interactions. By a graph theo- retic clustering algorithm Molecular Complex Detection （MCODE）, 26 modules were identified and analyzed by Gene ontology （GO） enrichment. Two modules were associated with anti-inflammatory actions. The most interesting finding of this study was that the anti-in- flammatory effect of flavonoid compounds may be partly attributable to inhibite FOS, PTGS2 expression, inhibite of IL-1β release, and block the MAPK pathway and toll-like receptor pathway.