Sex hormone estrogen is one of the most active intrinsic angiogenesis regulators; its therapeutic use has been limited due to its carcinogenic potential. Plant-derived phytoestrogens are attractive alternatives, but reports on their angiogenic activities often lack in-depth analysis and sometimes are controversial. Herein, we report a data-mining study with the existing literature, using IPA system to classify and characterize phytoestrogens based on their angiogenic properties and pharmacological consequences. We found that pro-angiogenic phytoestrogens functioned predominantly as cardiovascular protectors whereas anti-angiogenic phytoestrogens played a role in cancer prevention and therapy. This bidirectional regulation were shown to be target-selective and, for the most part, estrogen-receptor-dependent. The transactivation properties of ERα and ERβ by phytoestrogens were examined in the context of angiogenesis-related gene transcription. ERα and ERβ were shown to signal in opposite ways when complexed with the phytoestrogen for bidirectional regulation of angiogenesis. With ERα, phytoestrogen activated or inhibited transcription of some angiogenesis-related genes, resulting in the promotion of angiogenesis, whereas, with ERβ, phytoestrogen regulated transcription of angiogenesis-related genes, resulting in inhibition of angiogenesis. Therefore, the selectivity of phytoestrogen to ERα and ERβ may be critical in the balance of pro- or anti-angiogenesis process.
LIU Hai-XinWANG YuLU QingYANG Ming-ZhuFAN Guan-WeiKARAS Richard HGAO Xiu-MeiZHU Yan
关于中药的抗衰老功效,已经有许多相关报道,但是对于其物质基础及作用机制尚未明确阐明。腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)是能量代谢的感受器,能够延长寿命这一效应,在不同实验中都得到相应的证实。过表达或用二甲双胍激活AAK-2/AMPK均有延长线虫、果蝇寿命的功效。AMPK抗衰老的可能下游通路包括TOR/S6k途径、FOXOs途径、CRTC途径等。中医药核心理念之一为治未病,其表现之一即是以药食同源方式改善机体,由此达到长寿的目的。部分药食同源药物有可能通过激活AMPK以达到养生,延长寿命的目的。经过总结发现,相关中药复方中丹参、黄芪、黄连、茯苓、白术、大黄、人参使用频率较高,并且补虚活血类药物占主导。采用ingenuity pathway analysis(IPA)网络药理学软件分析,间接作用于AMPK靶蛋白而非其上下游通路的单体药物有黄连素、大黄素、姜黄素、白藜芦醇、虫草素、牛蒡子苷元等6个,在一定程度上说明药食同源药物通过AMPK通路延长寿命的可行性。该文综合数据库查询和IPA网络药理学软件分析对具有激活AMPK通路来延缓衰老功能的中药单体及组分进行了归纳和总结,并基于中医药"药食同源"的理念将这些药物可能通过改善能量代谢对于延缓衰老的影响进行了展望。
