Authentication of Brazilian Ginseng using Bar-HRM analysis

Abstract Hebanthe eriantha (Martius) Kuntze and Pfaffia glomerata (Spreng) Pedersen are medicinal plants popularly known as "Brazilian Ginseng" due to their similarity to Panax ginseng. In Brazil, they are sold as the same herb, despite their different pharmacological and toxicological properties. The morphological identification is difficult, which facilitates their adulteration. We report the application of the Barcode DNA High-Resolution Melting (Bar-HRM) using matK gene to differentiate both species in samples sold in the Brazilian market. Using the proposed method, we could discriminate and identify both species. Bar-HRM analysis allowed discriminating and identifying both species. It allowed the identification of H. eriantha and P. glomerata in 43.6% and 56.4% of the amplified samples, respectively. Of these, only seven samples were authenticated and, in 71.4% of the cases, adulterated. We concluded that Bar-HRM has proven to be a fast alternative method to authenticate plants under the common name "Brazilian Ginseng".

Evolutionary Contribution of Duplicated Genes to Genome Evolution in the Ginseng Species Complex.

Genes duplicated by whole genome duplication (WGD) and small-scale duplication (SSD) have played important roles in adaptive evolution of all flowering plants. However, it still remains underinvestigated how the distinct models of duplication events and their contending evolutionary patterns have shaped the genome and epigenomes of extant plant species. In this study, we investigated the contribution of the WGD- and SSD-derived duplicate genes to the genome evolution of one diploid and three closely related allotetraploid Panax species based on genome, methylome, and proteome data sets. Our genome-wide comparative analyses revealed that although the ginseng species complex was recently diverged, they have evolved distinct overall patterns of nucleotide variation, cytosine methylation, and protein-level expression. In particular, genetic and epigenetic asymmetries observed in the recent WGD-derived genes are largely consistent across the ginseng species complex. In addition, our results revealed that gene duplicates generated by ancient WGD and SSD mechanisms exhibited distinct evolutionary patterns. We found the ancient WGD-derived genes (i.e., ancient collinear gene) are genetically more conserved and hypomethylated at the cytosine sites. In contrast, some of the SSD-derived genes (i.e., dispersal duplicated gene) showed hypermethylation and high variance in nucleotide variation pattern. Functional enrichment analyses of the duplicated genes indicated that adaptation-related traits (i.e., photosynthesis) created during the distant ancient WGDs are further strengthened by both the more recent WGD and SSD. Together, our findings suggest that different types of duplicated genes may have played distinct but relaying evolutionary roles in the polyploidization and speciation processes in the ginseng species complex.

Structural-fingerprinting of polysaccharides to discern Panax species by means of gas-liquid chromatography and mass spectrometry.

In this paper, a sequential gas-liquid chromatography and mass spectrometry route was proposed for characterization of polysaccharides in Panax ginseng (PG), P. notoginseng (PN), and P. quinquefolius (PQ). Due to the reflection of stepped structure parameters, the resulting integrative profiles were tentatively defined as structural-fingerprinting of polysaccharides (SFP) with monosaccharide compositional fingerprinting (MCF), Smith degradation and non-degradation fingerprinting (SDF and SNF), and oligosaccharide compositional fingerprinting (OCF). The MCF, OCF and SDF did not allow for visual discrimination of the three species due to the high interspecific similarity of PG and PQ, whereas SNF could intuitively distinguish PG, PN, and PQ by the presence or absence of Rha and the peak area ratio of Glc/Gal. Similarity analysis, heatmap analysis and principal component analysis were further performed to discern three Panax species based on SNF data sets. The linear →4)-Hexp-(1 â†’ structures were clearly identified as the common structural backbones in side chains or smooth regions of the main chain in PPG, PPN, and PPQ using HILIC-UHPLC-ESI--MS/MS for characterization of partial acid hydrolyzates. The experimental results displayed that the established SFP approach possesses high comprehensibility as well as satisfactory generalization capability for analysis of plant polysaccharides.

Review: Molecular techniques to assess genetic variation within and between Panax ginseng and Panax quinquefolius.

A variety of methods have been used to examine genetic differences in P. ginseng and P. quinquefolius. They have shown genetic differences within populations of P. ginseng (within and between elite cultivars, landraces and wild accessions), within populations of P. quinquefolius (within and between wild and cultivated accessions) and between P. ginseng and P. quinquefolius as well as other Panax species. Some examples of their applications have been to show that some elite cultivars are not uniform, there are possible founder effects in certain populations, there has been the spread of cultivated types into wild populations, relative diversity differs between different populations and identification of the source and purity of commercial samples. More work in the use of molecular markers for ginseng are needed, however, particularly the use of Next Generation Sequencing. Potential applications are the use of sequence analysis for genetic selection, breeding to develop new cultivars and providing traceability from field to consumer. Research on molecular markers in ginseng has lagged compared to other crops probably because of less of an emphasis on breeding for cultivar development and relatively small areas of production. The many potential benefits for ginseng production have yet to be realized.

Novel Foveavirus (the family Betaflexiviridae) species identified in ginseng (Panax ginseng).

Ginseng (Panax ginseng) is a valuable herb that is widely cultivated in Korea, China, and Japan because it contains a variety of pharmacologically active substances with a wide range of positive effects on human health. Identification and prevention of disease-causing viral pathogens of ginseng is important for improving the yield and quality of ginseng-derived bioactive molecules. In this study, the genome sequence of the virus Panax ginseng flexivirus 1 (PgFV1) was identified from a ginseng root transcriptome data set. Sequence comparison and phylogenetic analysis showed that PgFV1 is a novel plant RNA virus species of the genus Foveavirus (the family Betaflexiviridae). Foveaviruses have flexuous and filamentous virions with a single-stranded positive-sense mono-segmented RNA genome. Its infection causes diseases with mosaic and ringspot symptoms in the stems and leaves. The PgFV1 genome encodes for 5 open reading frames: a replicase polyprotein for viral genome replication, 3 triple gene block proteins for viral cell-to-cell movement, and coat protein. Phylogenetic trees inferred from replicase polyprotein or coat protein sequences showed that PgFV1 is most closely related to grapevine virus T. PgFV1 is the first foveavirus identified to be associated with ginseng. Given the potential pathogenic features of previously known foveaviruses and importance of ginseng in the health industry, the PgFV1 genome sequence may be highly useful for studying ginseng foveaviruses. Keywords: ginseng; Panax ginseng flexivirus 1; Foveavirus; Betaflexiviridae.

Black Ginseng and Its Saponins: Preparation, Phytochemistry and Pharmacological Effects.

Black ginseng is a type of processed ginseng that is prepared from white or red ginseng by steaming and drying several times. This process causes extensive changes in types and amounts of secondary metabolites. The chief secondary metabolites in ginseng are ginsenosides (dammarane-type triterpene saponins), which transform into less polar ginsenosides in black ginseng by steaming. In addition, apparent changes happen to other secondary metabolites such as the increase in the contents of phenolic compounds, reducing sugars and acidic polysaccharides in addition to the decrease in concentrations of free amino acids and total polysaccharides. Furthermore, the presence of some Maillard reaction products like maltol was also engaged. These obvious chemical changes were associated with a noticeable superiority for black ginseng over white and red ginseng in most of the comparative biological studies. This review article is an attempt to illustrate different methods of preparation of black ginseng, major chemical changes of saponins and other constituents after steaming as well as the reported biological activities of black ginseng, its major saponins and other metabolites.

American Ginseng and Asian Ginseng Intervention in Diet-Induced Obese Mice: Metabolomics Reveals Distinct Metabolic Profiles.

American ginseng and Asian ginseng, which occupy prominent positions in the list of best-selling natural products in the West and East, are suitable for different indications in the traditional pharmacological uses. Currently, the effects of American ginseng and Asian ginseng in the protection against metabolic dysfunction and the differences between them are still unknown. Herein, an untargeted metabolomics based on liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) was determined. The serum metabolomics and dynamic feces metabolomics revealed significant metabolic distinction between American ginseng and Asian ginseng in diet-induced obese (DIO) mice. The results show that American ginseng and Asian ginseng alleviate glucose and lipid metabolism disorder in DIO mice. A total of 45 differential metabolites were confirmed between the drug-naïve and American ginseng group, and 32 metabolites were confirmed between the drug-naïve and Asian ginseng group. Metabolic pathways analysis shows that these two ginsengs treatment dynamic rectifies metabolic disorder in DIO mice mainly via regulating linoleic acids metabolism, cysteine and methionine metabolism and biosynthesis of unsaturated fatty acid. Moreover, American ginseng's specific function in monitoring the carnitines and taurine/hypotaurine metabolism might make it more effective in meliorating lipids metabolism disorder than Asian ginseng.

Explosively Puffed Ginseng Ameliorates Ionizing Radiation-Induced Injury of Colon by Decreasing Oxidative Stress-Related Apoptotic Cell Execution in Mice.

Although radiation therapy (RT) is a feasible treatment approach for early colorectal cancer, RT is considerably toxic to normal tissues due to the increased reactive oxygen species production, which can induce tissue damage. Ginseng, a natural antioxidant agent, exhibits the protective effects against ionizing radiation (IR)-induced damage in in vitro and in vivo models. The explosive puffing of ginseng has been investigated as a process to improve the efficacy of ginseng due to the resulting physicochemical changes in its functional components. In this study, we provided the evidence for promotion in the beneficial role of puffed ginseng extract (PGE) and associated mechanisms of action, in comparison with white ginseng extract (WGE), against IR-induced colorectal injury, using in vivo study on a mouse model. To study the role of PGE in preventing IR-induced damage, we examined colorectal injury and apoptotic changes in mice exposed to 137Cs at 8 Gy. High-performance liquid chromatography analysis showed that PGE had an increased total ginsenoside concentration with new generation of Rg3, Rg5, and Rk1, compared with the concentrations in WGE. Administering PGE, but not WGE, significantly ameliorated IR-induced colorectal cell death through negative regulation of apoptotic signaling pathways. These antiapoptotic effects of PGE were linked to the capacity to suppress the p53-mediated DNA damage response and NF-κB-mediated apoptotic signaling. Moreover, IR-induced oxidative stress in the colorectal epithelium was markedly reduced by PGE administration. Collectively, this study establishes a mechanism of action by which PGE counteracts IR-induced colorectal injury as a novel radioprotective agent.

Panax ginseng and Panax quinquefolius: From pharmacology to toxicology.

The use of Panax ginseng and Panax quinquefolius in traditional Chinese medicine dates back to about 5000 years ago thanks to its several beneficial and healing properties. Over the past few years, extensive preclinical and clinical evidence in the scientific literature worldwide has supported the beneficial effects of P. ginseng and P. quinquefolius in significant central nervous system, metabolic, infectious and neoplastic diseases. There has been growing research on ginseng because of its favorable pharmacokinetics, including the intestinal biotransformation which is responsible for the processing of ginsenosides - contained in the roots or extracts of ginseng - into metabolites with high pharmacological activity and how such principles act on numerous cell targets. The aim of this review is to provide a simple and extensive overview of the pharmacokinetics and pharmacodynamics of P. ginseng and P. quinquefolius, focusing on the clinical evidence which has shown particular effectiveness in specific diseases, such as dementia, diabetes mellitus, respiratory infections, and cancer. Furthermore, the review will also provide data on toxicological factors to support the favorable safety profile of these medicinal plants.

The ginseng's fireness is associated with the lowering activity of liver Na(+)-K(+)-ATPase.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng is an herbal medicine used worldwide that possesses a wide range of pharmacological activities. However, its side effects are rarely discussed. The experience of Chinese medicine has revealed that taking ginseng at a high dose chronically can cause fireness, i.e., the ginseng-abuse syndrome. Here, we explored the mechanism of ginseng's fireness by comparing the energy metabolism of mice affected by red ginseng (RG), ginseng (GS), ginseng leaves (GL) and American ginseng (AG), which exhibit different drug properties according to the theory of TCM. MATERIALS AND METHODS: KM mice were randomly divided into five groups (n≥30 per group) and administered distilled water or drugs, respectively. Mice receiving RG, GS, or GL received 4.5g/(kgday), while the mice receiving AG received 3g/(kgday). Control mice received distilled water. The duration of exposure for all groups was 31 days. The mice's physical characteristics, such as eye condition, rectal temperature, saliva secretion, urine, stool weight, blood coagulation time and swimming time, were measured at different times after administration. Energy metabolism indexes were measured via TSE phenoMaster/LabMaster animal monitoring system, including the mice' 24h oxygen consumption (VO2), carbon dioxide production (VCO2), heat production (H) and energy expenditure (EE). Biochemical indices were measured by ultraviolet spectrophotometer and microplate reader, including pyruvic acid content in serum and succinate dehydrogenase (SDH) activity, lactate dehydrogenase (LDH) activity, the Na(+)-K(+)-ATPase activity and the content of glycogen in the liver tissue. RESULTS: After 31 days of drug administration, mice in the RG and GS groups exhibited obviously more eye secretions, less saliva secretion and less urine. Compared with the control group, the swimming times of mice in the GS, AG and GL groups were significantly prolonged; the clotting time of mice in the GL was extended significantly; VCO2, H and EE of mice in the GS group were obviously increased; Pyruvate content of mice in the RG group showed an initial decrease followed by an increase; SDH activity of mice in the AG and GL groups was significantly inhibited; LDH activity of the mice showed no significant difference among different groups; Na(+)-K(+)-ATP enzyme activity of the RG and GS groups showed up-regulation initially and then down-regulation; the content of hepatic glycogen of mice in the GS and GL groups increased significantly. CONCLUSION: The results demonstrated that RG and GS with their warm drug nature could enhance the body's energy metabolism to produce their dryness to the body. The liver Na(+)-K(+)-ATP enzyme activity may be the primary index for indicating the fireness of ginseng. In addition, our results demonstrated that ginseng, especially red ginseng, is not suitable for long time application with a higher dose.

Saponins in the genus Panax L. (Araliaceae): a systematic review of their chemical diversity.

The Panax genus is a crucial source of natural medicines that has benefited human health for a long time. Three valuable medicinal herbs, namely Panax ginseng, Panax quinquefolius, and Panax notoginseng, have received considerable interest due to their extensive application in clinical therapy, healthcare products, and as foods and food additives world-wide. Panax species are known to contain abundant levels of saponins, also dubbed ginsenosides, which refer to a series of dammarane or oleanane type triterpenoid glycosides. These saponins exhibit modulatory effects to the central nervous system and beneficial effects to patients suffering from cardiovascular diseases, and also have anti-diabetic and anti-tumor properties. To the end of 2012, at least 289 saponins were reported from eleven different Panax species. This comprehensive review describes the advances in the phytochemistry of the genus Panax for the period 1963-2012, based on the 134 cited references. The reported saponins can be classified into protopanaxadiol, protopanaxatriol, octillol, oleanolic acid, C17 side-chain varied, and miscellaneous subtypes, according to structural differences in sapogenins. The investigational history of Panax is also reviewed, with special attention being paid to the structural features of the six different subtypes, together with their (1)H and (13)C NMR spectroscopic characteristics which are useful for determining their structures and absolute configuration.

Efficacy comparison of Korean ginseng and American ginseng on body temperature and metabolic parameters.

Ginseng has beneficial effects in cancer, diabetes and aging. There are two main varieties of ginseng: Panax ginseng (Korean ginseng) and Panax quinquefolius (American ginseng). There are anecdotal reports that American ginseng helps reduce body temperature, whereas Korean ginseng improves blood circulation and increases body temperature; however, their respective effects on body temperature and metabolic parameters have not been studied. We investigated body temperature and metabolic parameters in mice using a metabolic cage. After administering ginseng extracts acutely (single dose of 1000 mg/kg) or chronically (200 mg/kg/day for four weeks), core body temperature, food intake, oxygen consumption and activity were measured, as well as serum levels of pyrogen-related factors and mRNA expression of metabolic genes. Acute treatment with American ginseng reduced body temperature compared with PBS-treated mice during the night; however, there was no significant effect of ginseng treatment on body temperature after four weeks of treatment. VO 2, VCO 2, food intake, activity and energy expenditure were unchanged after both acute and chronic ginseng treatment compared with PBS treatment. In acutely treated mice, serum thyroxin levels were reduced by red and American ginseng, and the serum prostaglandin E2 level was reduced by American ginseng. In chronically treated mice, red and white ginseng reduced thyroxin levels. We conclude that Korean ginseng does not stimulate metabolism in mice, whereas a high dose of American ginseng may reduce night-time body temperature and pyrogen-related factors.

[Advances in the study of derivatization of ginsenosides and their anti-tumor structure-activity relationship].

Ginsenosides, belonging to a group of saponins with triterpenoid dammarane skeleton, show a variety of pharmacological effects. Among them, some ginsenoside derivatives, which can be produced by acidic and alkaline hydrolysis, biotransformation and steamed process from the major ginsenosides in ginseng plant, perform stronger activities than the major primeval ginsenosides on inhibiting growth or metastasis of tumor, inducing apoptosis and differentiation of tumor and reversing multidrug resistance of tumor. Therefore ginsenoside derivatives are promising as antitumor active compounds and drugs. In this review, the derivatization methods, ginsenoside derivatives and their anti-tumor structure-activity relationship have been summarized for providing useful information for the research and development of novel antitumor drugs.

Eficiência da absorção, translocação e uso de N e P pela Pfaffia glomerata (Spreng. ) Pedersen / Efficiency of N and P uptake, translocation and use by Pfaffia glomerata (Spreng. ) Pedersen

Tendo como objetivo avaliar a eficiência de absorção, translocação e uso de nitrogênio (N) e fósforo (P) pela Pfaffia glomerata, foi conduzido o presente trabalho em casa de vegetação no delineamento inteiramente casualizado com três repetições. Os tratamentos foram dispostos em esquema fatorial 5 x 5, sendo cinco doses de N (0, 125, 250, 375 e 500 mg vaso-1) e cinco doses de P (P2O5) (0, 125, 250, 375 e 500 mg vaso-1). Os resultados evidenciaram que a eficiência de absorção de N e P foi influenciada pelas doses de N e P utilizadas no experimento apresentando interação entre os fatores em estudo. A eficiência de translocação do N foi consideravelmente menor que a de P, provavelmente pela maior concentração de compostos nitrogenados nas raízes em detrimento da parte aérea. Observou-se maior eficiência de uso do P devido à menor concentração desse elemento na planta. A absorção de N e de P foi influenciada pela dose desses elementos no solo, sendo possível a estimativa das doses desses nutrientes que proporcionem maiores eficiências de absorção, translocação, uso e teor total.

Aimed at evaluating the efficiency of nitrogen (N) and phosphorus (P) uptake, translocation and use by Pfaffia glomerata, the present study was conducted in greenhouse, in completely randomized design with three replicates. Treatments were displayed in 5 x 5 factorial design, with five N levels (0, 125, 250, 375 and 500 mg pot-1) and five P (P2O5) levels (0, 125, 250, 375 and 500 mg pot-1). Results evidenced that N and P uptake efficiency was influenced by the N and P levels used in the experiment, showing interaction among the studied factors. N translocation efficiency was considerably lower than that of P, probably due to the lower concentration of nitrogenous compounds in the roots than in the shoot. P use efficiency was higher due to the lower concentration of this element in the plant. N and P uptake was influenced by the level of these elements in the soil, being possible to estimate the levels of these nutrients which provide higher uptake, translocation and use efficiency besides total content.

Cellular uptake of ginsenosides in Korean white ginseng and red ginseng and their apoptotic activities in human breast cancer cells.

Panax ginseng has been reported to have cancer-preventive properties and, through anti-inflammatory, antioxidant, and pro-apoptotic mechanisms, to influence gene expression. However, the comparison of Korean white ginseng (WG) and red ginseng (RG) in their apoptotic effects and the identification of the selective cellular uptake of the ginsenosides in human breast cancer cells have not yet been fully understood. In the present study, the relative nonpolar and protopanaxadiol (PPD) class ginsenosides exhibited more cytotoxic and efficient cellular uptake on MCF-7 cells compared with the relative polar and protopanaxatriol (PPT) class compounds. PPD class ginsenosides were present in RG in a 2.5 times higher concentration as compared to WG, while PPT class ginsenosides were only present in WG. Thus, RG exerted more potent cytotoxicity than WG against MCF-7 and MDA-MB231 cells. RG also increased the sub-G1 DNA contents of the cell cycle and Annexin V-positive apoptotic bodies undergoing apoptosis through the caspase-3 activation in MCF-7 cells. In addition, RG downregulated the proliferative and anti-apoptotic gene products and potentiated paclitaxel-induced apoptosis in MCF-7 cells. Overall, RG contained a higher concentration of PPD class ginsenosides as compared to WG; the greater cellular uptake of PPD resulted in more substantial antiproliferative activity in human breast cancer cells.

Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium.

Medical application of Panax ginseng was first found in "Shen-Nong Herbal Classic"around 200 AD Panax quinquefolium was first introduced in "Essential of Materia Medica" in 1694 in China. The most important bioactive components contained in P ginseng and P quinquefolium are ginseng saponins (GS). The contents of ginsenoside Rb1, Re, and Rd in P quinquefolium are higher than they are in P ginseng. In P ginseng, the contents of Rg1,Rb2, and Rc are higher than they are in P quinquefolium. P ginseng had a higher ratio of Rg1: Rb1, and which was lower in P quinquefolium. After steaming for several hours, the total GS will decrease. However, some ginsenosides (Rg2, 20R-Rg2, Rg3, Rh1 and Rh2) increase, while others (Rb1, Rb2, Rb3, Rc, Rd, Re, and Rg1) decrease. However, variation, especially in P quinquefolium, is high. P ginseng and P quinquefolium are general tonics and adaptogens. Rg1 and Rb1 enhance central nervous system (CNS) activities, but the effect of the latter is weaker. Thus, for the higher contents of Rg1, P ginseng is a stimulant, whereas the Rb1 contents of P quinquefolium are mainly calming to the CNS. Re, Rg1, panaxan A and B from P ginseng are good for diabetes. Re and Rg1 enhance angiogenesis, whereas Rb1, Rg3 and Rh2 inhibit it. Rh2, an antitumor agent, can be obtained from Rb1 by steaming. The content of Re in P quinquefolium are higher than in P ginseng by 3-4 times. The vasorelax, antioxidant, antihyperlipidemic, and angiogenic effects of Re are reported. Thus, for the CNS "hot," wound healing and hypoglycemic effects, P ginseng is better than P quinquefolium. For anticancer effects, P quinquefolium is better.

[Determination of organochlorine pesticides redidues in traditional Chinese medicine including ginseng or American ginseng].

OBJECTIVE: To determine the residues of 19 organochlorine pesticides in traditional chinese medicine (TCM) including Radix ginseng or Radix panacis quinquefolii by capillary gas chromatograrhy. METHODS: The samples were extracted with ethyl acetate by ultrasonic, then cleaned up by a column packed with Florisil. The capillary column was DB-1701 (30 m x 0.32 m, 0.25 microm). The electron capture detector (ECD) was used. The pesticide residues were calculated by external standard method. RESULTS: The average recoveries and RSD ranged from 70.4% to 125.0% and 3.16% to 9.86%. CONCLUSION: The method is rapid, simple and accurate. It can be used to determine organochlorine pesticide residues in TCM.

Identification and differentiation of Panax species using ELISA, RAPD and eastern blotting.

Immunochemical and genetic methods have been developed in order to distinguish Panax spp. With the aim of establishing immunochemical methods, two hybridomas (3H4 and 5H8), each secreting a monoclonal antibody (MAb) against proteins of Panax ginseng, were prepared by fusing splenocytes immunized with two kinds of ginseng water-soluble fractions and a hypoxanthine-thymidine-aminopterin-sensitive mouse myeloma cell line, P3-X63-Ag8-U1. MAb 3H4 cross-reacted with four Panax spp., whereas the MAb 5H8 cross-reacted with P. ginseng in the enzyme-linked immunosorbent assay (ELISA). ELISA and western blotting methods using a ginseng water-soluble fraction as the solid-phase antigen were developed for the unambiguous authentication of P. ginseng. A combination of random amplified polymorphic DNA (RAPD) and eastern blotting analyses using anti-ginsenoside Rb1 and Rgl monoclonal antibodies was used for the identification of P. notoginseng, P. quinquefolius and P. japonicus. RAPD can be used to differentiate the species of Panax from each other. An important parameter used for differentiating P. notoginseng is the absence of ginsenoside Rc in the extract of P. notoginseng with eastern blotting. The combination of these methods enabled a reliable identification of Panax spp.

Modulating angiogenesis: the yin and the yang in ginseng.

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.

Panax ginseng--a non-organ-specific cancer preventive?

For the past 50 years, the main weapons in the war against cancer have been early detection and surgical removal, radiotherapy, chemotherapy, and attempts to develop gene therapy. However, the results so far are less than ideal. One strategy now is to switch from therapeutic approaches to prevention of cancer by improving lifestyle and by identifying effective natural products as chemopreventive agents. One promising candidate with cancer-preventive effects that are not specific to any organ is Panax ginseng C A Meyer, a herb with a long medicinal history. Its protective influence against cancer has been shown by extensive preclinical and epidemiological studies, but these effects need to be carefully investigated by scientific clinical trials focusing on the major cancer killers stomach, lung, liver, and colorectal cancer.