Modulating angiogenesis: The yin and the yang in ginseng
| Autor: | Sengupta, S., Toh, S.A., Sellers, L.A., Skepper, J.N., Koolwijk, P., Leung, H.W., Yeung, H.W., Wong, R.N.S., Sasisekharan, R., Fan, T.P.D. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Male
Surgical Sponges Umbilical Veins Biomedical Research Ginsenosides wound healing Angiogenesis Inhibitors antiangiogenic activity ginseng polysaccharide Mice 1-Phosphatidylinositol 3-Kinase phosphatidylinositol 3 kinase endothelium cell Enzyme Inhibitors law panax quinquefolium extract Cells Cultured mass spectrometry Drug Implants sterol derivative Molecular Structure Neovascularization Pathologic nitric oxide synthase drug effect species differentiation drug identification cell invasion NG-Nitroarginine Methyl Ester herbal medicine Signal Transduction China Spectrometry Mass Electrospray Ionization drug isolation in vitro study phenotype regulatory mechanism polymer animal experiment Panax in vivo study Species Specificity drug mechanism chemical composition Animals Humans controlled study drug screening Biology protein expression standardization nonhuman Korea animal model human cell Endothelial Cells Nitric oxide Panax notoginseng extract neovascularization (pathology) human tissue Mice Inbred C57BL herbaceous agent drug structure cell proliferation chemical analysis protein kinase B Angiogenesis Inducing Agents Angiogenesis Endothelium Vascular Americas ginseng extract Phytotherapy |
| Zdroj: | Circulation, 10, 110, 1219-1225 |
| Popis: | 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. Chemicals / CAS: nitric oxide synthase, 125978-95-2; phosphatidylinositol 3 kinase, 115926-52-8; protein kinase B, 148640-14-6; 1-Phosphatidylinositol 3-Kinase, EC 2.7.1.137; Angiogenesis Inducing Agents; Angiogenesis Inhibitors; Drug Implants; Enzyme Inhibitors; ginsenoside Rb1; ginsenoside Rg1, 22427-39-0; Ginsenosides; NG-Nitroarginine Methyl Ester, 50903-99-6 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|