Review

Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides

Patrick Ying Kit Yue¹ , Nai Ki Mak¹ , Yuen Kit Cheng² , Kar Wah Leung¹ , Tzi Bun Ng³ , David Tai Ping Fan⁴ , Hin Wing Yeung⁵ and Ricky Ngok Shun Wong¹

¹Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China

²Department of Chemistry, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China

³Department of Biochemistry, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China

⁴Angiogenesis & TCM Laboratory, Department of Pharmacology, University of Cambridge, Tennis Court Road, CB2 1PD, UK

⁵International Society for Chinese Medicine, A & C, 1^st floor, Block 2, University of Macau, Av. Padre Tomas Pereira, Taipa, Macao SAR, China

author email corresponding author email

Chinese Medicine 2007, 2:6doi:10.1186/1749-8546-2-6

Published:	15 May 2007

Abstract

In Chinese medicine, ginseng (Panax ginseng C.A. Meyer) has long been used as a general tonic or an adaptogen to promote longevity and enhance bodily functions. It has also been claimed to be effective in combating stress, fatigue, oxidants, cancer and diabetes mellitus. Most of the pharmacological actions of ginseng are attributed to one type of its constituents, namely the ginsenosides. In this review, we focus on the recent advances in the study of ginsenosides on angiogenesis which is related to many pathological conditions including tumor progression and cardiovascular dysfunctions.

Angiogenesis in the human body is regulated by two sets of counteracting factors, angiogenic stimulators and inhibitors. The 'Yin and Yang' action of ginseng on angiomodulation was paralleled by the experimental data showing angiogenesis was indeed related to the compositional ratio between ginsenosides Rg₁ and Rb₁. Rg₁ was later found to stimulate angiogenesis through augmenting the production of nitric oxide (NO) and vascular endothelial growth factor (VEGF). Mechanistic studies revealed that such responses were mediated through the PI3K→Akt pathway. By means of DNA microarray, a group of genes related to cell adhesion, migration and cytoskeleton were found to be up-regulated in endothelial cells. These gene products may interact in a hierarchical cascade pattern to modulate cell architectural dynamics which is concomitant to the observed phenomena in angiogenesis. By contrast, the anti-tumor and anti-angiogenic effects of ginsenosides (e.g. Rg₃ and Rh₂) have been demonstrated in various models of tumor and endothelial cells, indicating that ginsenosides with opposing activities are present in ginseng. Ginsenosides and Panax ginseng extracts have been shown to exert protective effects on vascular dysfunctions, such as hypertension, atherosclerotic disorders and ischemic injury. Recent work has demonstrates the target molecules of ginsenosides to be a group of nuclear steroid hormone receptors. These lines of evidence support that the interaction between ginsenosides and various nuclear steroid hormone receptors may explain the diverse pharmacological activities of ginseng. These findings may also lead to development of more efficacious ginseng-derived therapeutics for angiogenesis-related diseases.