Modulating angiogenesis - The yin and the yang in ginseng
Modulating angiogenesis - The yin and the yang in ginseng
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DOI：
10.1161/01.cir.0000140676.88412.cf
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发表时间：
2004-09-01
期刊：
影响因子：
37.8
通讯作者：
Fan, TPD
中科院分区：
文献类型：
--
作者：
Sengupta, S;Toh, SA;Fan, TPD
背景-人参是一种常用的营养食品。有趣的是，现有的文献报道了人参提取物通过对血管系统的相反作用而产生的伤口愈合和抗肿瘤作用。为了阐明这一困惑，我们将化学指纹图谱方法与从人参提取物中提取的纯分子对血管生成影响的解构研究相结合。方法和结果-对美国、中国和韩国人参以及三七人参进行了质谱成分分析，发现了明显的“甾醇人参皂苷”指纹图谱，特别是三醇Rg1和二醇Rb1之间的比例。使用Matrigel植入模型并使用两种人参皂苷的不同比例重建提取物，我们证明了Rg1的优势导致血管生成，而Rb1发挥相反的作用。Rg1还在体内促进功能性新生血管进入聚合物支架，并在体外促进内皮细胞的增殖、化学侵袭和小管形成，这一作用是通过一氧化氮合酶和磷脂酰肌醇-3激酶-GT；Akt途径介导的。相反，Rb1抑制血管生成的最早步骤，即内皮细胞的化学侵袭。结论-本研究首次解释了人参在血管病理生理学中的作用的模棱两可，这是基于人参提取物中存在相反的活性成分。我们还揭示了一种影响成分指纹的特殊地理变异，这种变异可能影响最终的表型。这强调了目前根据《膳食补充和健康教育法》对草药疗法进行标准化的法规的必要性。此外，我们认为Rg1可能是一组新的非肽分子的原型，可以诱导治疗性血管生成，例如在伤口愈合中。
Background-Ginseng is a commonly used nutraceutical. Intriguingly, existing literature reports both wound-healing and antitumor effects of ginseng extract through opposing activities on the vascular system. To elucidate this perplexity, we merged a chemical fingerprinting approach with a deconstructional study of the effects of pure molecules from ginseng extract on angiogenesis.Methods and Results-A mass spectrometric compositional analysis of American, Chinese and Korean, and Sanqi ginseng revealed distinct "sterol ginsenoside" fingerprints, especially in the ratio between a triol, Rg1, and a diol, Rb1, the 2 most prevalent constituents. Using a Matrigel implant model and reconstituting the extracts using distinct ratios of the 2 ginsenosides, we demonstrate that the dominance of Rg1 leads to angiogenesis, whereas Rb1 exerts an opposing effect. Rg1 also promoted functional neovascularization into a polymer scaffold in vivo and the proliferation of, chemoinvasion of, and tubulogenesis by endothelial cells in vitro, an effect mediated through the expression of nitric oxide synthase and the phosphatidylinositol-3 kinase-->Akt pathway. In contrast, Rb1 inhibited the earliest step in angiogenesis, the chemoinvasion of endothelial cells.Conclusions-The present study explains, for the first time, the ambiguity about the effects of ginseng in vascular pathophysiology based on the existence of opposing active principles in the extract. We also unraveled a speciogeographic variation impinging on the compositional fingerprint that may modulate the final phenotype. This emphasizes the need for regulations standardizing herbal therapy, currently under the Dietary Supplement and Health Education Act. Furthermore, we propose that Rg1 could be a prototype for a novel group of nonpeptide molecules that can induce therapeutic angiogenesis, such as in wound healing.