Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Acta Pharmacol Sin. 2018 Jun;39(6):961-974. doi: 10.1038/aps.2017.145. Epub 2018 Jan 18.
Both baicalin (BA) and jasminoidin (JA) are active ingredients in Chinese herb medicine Scutellaria baicalensis and Fructus gardeniae, respectively. They have been shown to exert additive neuroprotective action in ischemic stroke models. In this study we used transcriptome analysis to explore the pure therapeutic mechanisms of BA, JA and their combination (BJ) contributing to phenotype variation and reversal of pathological processes. Mice with middle cerebral artery obstruction were treated with BA, JA, their combination (BJ), or concha margaritifera (CM). Cerebral infarct volume was examined to determine the effect of these compounds on phenotype. Using the hippocampus microarray and ingenuity pathway analysis (IPA) software, we exacted the differentially expressed genes, networks, pathways, and functions in positive-phenotype groups (BA, JA and BJ) by comparing with the negative-phenotype group (CM). In the BA, JA, and BJ groups, a total of 7, 4, and 11 specific target molecules, 1, 1, and 4 networks, 51, 59, and 18 canonical pathways and 70, 53, and 64 biological functions, respectively, were identified. Pure therapeutic mechanisms of BA and JA were mainly overlapped in specific target molecules, functions and pathways, which were related to the nervous system, inflammation and immune response. The specific mechanisms of BA and JA were associated with apoptosis and cancer-related signaling and endocrine and hormone regulation, respectively. In the BJ group, novel target profiles distinct from mono-therapies were revealed, including 11 specific target molecules, 10 functions, and 10 pathways, the majority of which were related to a virus-mediated immune response. The pure additive effects between BA and JA were based on enhanced action in virus-mediated immune response. This pure mechanistic analysis may provide a clearer outline of the target profiles of multi-target compounds and combination therapies.
黄芩苷（BA）和栀子苷（JA）分别是中药黄芩和栀子的活性成分，已被证明在缺血性中风模型中具有相加的神经保护作用。在这项研究中，我们使用转录组分析来探讨 BA、JA 及其组合（BJ）对表型变化和病理过程逆转的纯治疗机制。采用大脑中动脉阻塞模型，用 BA、JA、其组合（BJ）或珍珠贝（CM）对小鼠进行治疗。通过检测脑梗死体积，确定这些化合物对表型的影响。采用海马微阵列和 Ingenuity 通路分析（IPA）软件，通过与阴性表型组（CM）比较，从阳性表型组（BA、JA 和 BJ）中提取差异表达基因、网络、通路和功能。在 BA、JA 和 BJ 组中，共鉴定出 7、4 和 11 个特定靶标分子、1、1 和 4 个网络、51、59 和 18 个经典通路以及 70、53 和 64 个生物学功能。BA 和 JA 的纯治疗机制主要在特定靶标分子、功能和通路方面重叠，这些通路与神经系统、炎症和免疫反应有关。BA 和 JA 的具体机制分别与细胞凋亡和癌症相关信号以及内分泌和激素调节有关。在 BJ 组中，揭示了与单药治疗不同的新靶标谱，包括 11 个特定靶标分子、10 个功能和 10 个通路，其中大多数与病毒介导的免疫反应有关。BA 和 JA 之间的纯相加作用基于增强病毒介导的免疫反应。这种纯机制分析可能为多靶点化合物和联合疗法的靶标谱提供更清晰的轮廓。
