Discovery of molecular mechanisms of traditional Chinese medicinal formula Si-Wu-Tang using gene expression microarray and connectivity map.
Discovery of molecular mechanisms of traditional Chinese medicinal formula Si-Wu-Tang using gene expression microarray and connectivity map.
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DOI：
10.1371/journal.pone.0018278
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发表时间：
2011-03-28
期刊：
影响因子：
3.7
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Wen Z;Wang Z;Wang S;Ravula R;Yang L;Xu J;Wang C;Zuo Z;Chow MS;Shi L;Huang Y
为了寻求系统的方法来发现传统中药（TCM）的作用机制，我们使用微阵列、生物信息学和“连接图”（CMAP）来检查中药诱导的基因表达变化。我们证明，这种方法可用于利用广泛用于女性健康的中药草药配方四物汤（SWT）来阐明新的分子靶点。用 0.1 µM 雌二醇或 2.56 mg/ml SWT 处理的人乳腺癌 MCF-7 细胞显示出显着的基因表达变化，而阿魏酸（SWT 的一种已知生物活性化合物）没有检测到显着变化。使用与治疗效果相关的差异表达基因进行的通路分析发现，核因子红细胞2相关因子2 (Nrf2)细胞保护通路中的基因表达受SWT影响最显着，但不受雌二醇或阿魏酸的影响。 SWT 以剂量依赖性方式上调 Nrf2 调节基因 HMOX1、GCLC、GCLM、SLC7A11 和 NQO1，并通过实时 RT-PCR 进行了验证。一致的是，用 SWT 及其四种草药成分治疗可导致 MCF-7 和 HEK293 细胞中的抗氧化反应元件 (ARE)-荧光素酶报告活性增加。此外，将与SWT处理相关的差异表达基因的基因表达谱与CMAP数据库中1,309种化合物的基因表达谱进行比较。雌二醇处理的 MCF-7 细胞的 CMAP 谱显示与 SWT 治疗非常匹配，与 SWT 广泛声称的治疗女性疾病的用途一致，并表明其具有植物雌激素作用。化学预防剂 withaferin A 和白藜芦醇的 CMAP 谱也与 SWT 的谱有高度相似性。这项研究将 SWT 确定为 Nrf2 激活剂和植物雌激素，表明其可用作无毒化学预防剂，并证明了将微阵列基因表达谱与 CMAP 挖掘相结合以发现作用机制并确定中药新的健康益处的可行性。
To pursue a systematic approach to discovery of mechanisms of action of traditional Chinese medicine (TCM), we used microarrays, bioinformatics and the “Connectivity Map” (CMAP) to examine TCM-induced changes in gene expression. We demonstrated that this approach can be used to elucidate new molecular targets using a model TCM herbal formula Si-Wu-Tang (SWT) which is widely used for women's health. The human breast cancer MCF-7 cells treated with 0.1 µM estradiol or 2.56 mg/ml of SWT showed dramatic gene expression changes, while no significant change was detected for ferulic acid, a known bioactive compound of SWT. Pathway analysis using differentially expressed genes related to the treatment effect identified that expression of genes in the nuclear factor erythroid 2-related factor 2 (Nrf2) cytoprotective pathway was most significantly affected by SWT, but not by estradiol or ferulic acid. The Nrf2-regulated genes HMOX1, GCLC, GCLM, SLC7A11 and NQO1 were upreguated by SWT in a dose-dependent manner, which was validated by real-time RT-PCR. Consistently, treatment with SWT and its four herbal ingredients resulted in an increased antioxidant response element (ARE)-luciferase reporter activity in MCF-7 and HEK293 cells. Furthermore, the gene expression profile of differentially expressed genes related to SWT treatment was used to compare with those of 1,309 compounds in the CMAP database. The CMAP profiles of estradiol-treated MCF-7 cells showed an excellent match with SWT treatment, consistent with SWT's widely claimed use for women's diseases and indicating a phytoestrogenic effect. The CMAP profiles of chemopreventive agents withaferin A and resveratrol also showed high similarity to the profiles of SWT. This study identified SWT as an Nrf2 activator and phytoestrogen, suggesting its use as a nontoxic chemopreventive agent, and demonstrated the feasibility of combining microarray gene expression profiling with CMAP mining to discover mechanisms of actions and to identify new health benefits of TCMs.
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影响因子：
9.7
作者：
Gheeya J;Johansson P;Chen QR;Dexheimer T;Metaferia B;Song YK;Wei JS;He J;Pommier Y;Khan J
通讯作者：
Khan J
影响因子：
4.8
作者：
Krönke, G;Bochkov, VN;Leitinger, N
通讯作者：
Leitinger, N
影响因子：
4.3
作者：
Bancos, Simona;Baglole, Carolyn J.;Rahman, Irfan;Phipps, Richard P.
通讯作者：
Phipps, Richard P.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
5.4
作者：
Hsu, HY;Ho, YH;Lin, CC
通讯作者：
Lin, CC