Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
CNS Neurosci Ther. 2014 Mar;20(3):253-63. doi: 10.1111/cns.12205. Epub 2013 Dec 19.
Cerebral ischemia is considered to be a highly complex disease resulting from the complicated interplay of multiple pathways. Disappointedly, most of the previous studies were limited to a single gene or a single pathway. The extent to which all involved pathways are translated into fusing mechanisms of a combination therapy is of fundamental importance.
We report an integrative strategy to reveal the additive mechanism that a combination (BJ) of compound baicalin (BA) and jasminoidin (JA) fights against cerebral ischemia based on variation of pathways and functional communities.
We identified six pathways of BJ group that shared diverse additive index from 0.09 to 1, which assembled broad cross talks from seven pathways of BA and 16 pathways of JA both at horizontal and vertical levels. Besides a total of 60 overlapping functions as a robust integration background among the three groups based on significantly differential subnetworks, additive mechanism with strong confidence by networks altered functions.
These results provide strong evidence that the additive mechanism is more complex than previously appreciated, and an integrative analysis of pathways may suggest an important paradigm for revealing pharmacological mechanisms underlying drug combinations.
脑缺血被认为是一种高度复杂的疾病，是多种途径复杂相互作用的结果。令人失望的是，以前的大多数研究都局限于单个基因或单个途径。将所有涉及的途径转化为组合治疗的融合机制的程度至关重要。
我们报告了一种综合策略，基于途径和功能群落的变化，揭示了化合物黄芩苷（BA）和茉莉苷（JA）联合（BJ）对抗脑缺血的附加机制。
我们鉴定了 BJ 组的 6 条途径，它们的共享加性指数从 0.09 到 1 不等，这些途径在水平和垂直两个层面上整合了来自 BA 的 7 条途径和 JA 的 16 条途径的广泛交叉对话。除了三组之间基于显著差异子网络的总共 60 个重叠功能作为一个强大的综合背景外，网络改变功能的具有强置信度的附加机制。
这些结果提供了强有力的证据，表明附加机制比以前认为的更为复杂，对途径的综合分析可能为揭示药物组合的药理学机制提供一个重要的范例。
