Global deregulation of ginseng products may be a safety hazard to warfarin takers: solid evidence of ginseng-warfarin interaction.
ABSTRACT: Recent global deregulation of ginseng as the table food raises our concern about the possible ginseng-warfarin interaction that could be life-threatening to patients who take warfarin for preventing fatal strokes and thromboembolism while using ginseng products for bioenergy recovery. Here we show that quality-control ginsenosides, extracted from ginseng and containing its major active ingredients, produce dose- and time-dependent antagonism in rats against warfarin's anti-coagulation assessed by INR and rat thrombosis model. The interactions between ginsenosides and warfarin on thrombosis, pharmacokinetics, activities of coagulation factors and liver cytochrome P450 isomers are determined by using thrombosis analyzer, UPLC/MS/MS, ELISA and real-time PCR, respectively. The antagonism correlates well with the related pharmacokinetic interaction showing that the blood plateaus of warfarin reached by one-week warfarin administration are significantly reduced after three-week co-administration of warfarin with ginsenosides while 7-hydroxywarfarin is increased. The one-week warfarin and three-week warfarin-ginsenosides regimen result in restoring the suppressed levels by warfarin of the coagulating factors II, VII and protein Z, and significantly enhance activities of P450 3A4 and 2C9 that metabolize warfarin. The present study, for the first time, provides the solid evidence to demonstrate the warfarin-ginsenoside interaction, and warns the warfarin users and regulation authorities of the dangerous interaction.
Project description:Recently Panax ginseng has been grown as a secondary crop under a pine tree canopy in New Zealand (NZ). The aim of the study is to compare the average content of ginsenosides from NZ-grown ginseng and its original native locations (China and Korea) grown ginseng. Ten batches of NZ-grown ginseng were extracted using 70% methanol and analyzed using LC-MS/MS. The average content of ginsenosides from China and Korea grown ginseng were obtained by collecting data from 30 and 17 publications featuring China and Korea grown ginseng, respectively. The average content of total ginsenosides in NZ-grown ginseng was 40.06 ± 3.21 mg/g (n = 14), which showed significantly (p < 0.05) higher concentration than that of China grown ginseng (16.48 ± 1.24 mg/g, n = 113) and Korea grown ginseng (21.05 ± 1.57 mg/g, n = 106). For the individual ginsenosides, except for the ginsenosides Rb2, Rc, and Rd, ginsenosides Rb1, Re, Rf, and Rg1 from NZ-grown ginseng were 2.22, 2.91, 1.65, and 1.27 times higher than that of ginseng grown in China, respectively. Ginsenosides Re and Rg1 in NZ-grown ginseng were also 2.14 and 1.63 times higher than ginseng grown in Korea. From the accumulation of ginsenosides, New Zealand volcanic pumice soil may be more suitable for ginseng growth than its place of origin.
Project description:Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolium L.) are the two most important ginseng species for their medicinal properties. Ginseng is not only popular to consume, but is also increasingly popular to cultivate. In the North Island of New Zealand, Asian ginseng and American ginseng have been grown in Taupo and Rotorua for more than 15 years. There are no publications comparing the chemical constituents between New Zealand-grown Asian ginseng (NZPG) and New Zealand-grown American ginseng (NZPQ). In this study, fourteen ginsenoside reference standards and LC-MS2 technology were employed to analyze the ginsenoside components of various parts (fine root, rhizome, main root, stem, and leaf) from NZPG and NZPQ. Fifty and 43 ginsenosides were identified from various parts of NZPG and NZPQ, respectively, and 29 ginsenosides were found in both ginseng species. Ginsenoside concentrations in different parts of ginsengs were varied. Compared to other tissues, the fine roots contained the most abundant ginsenosides, not only in NZPG (142.49 ± 1.14 mg/g) but also in NZPQ (115.69 ± 3.51 mg/g). For the individual ginsenosides of both NZPG and NZPQ, concentration of Rb1 was highest in the underground parts (fine root, rhizome, and main root), and ginsenoside Re was highest in the aboveground parts (stem and leaf).
Project description:Ginseng is an increasingly popular ingredient in supplements for healthcare products and traditional medicine. Heat-processed ginsengs, such as red ginseng or black ginseng, are regarded as more valuable for medicinal use when compared to white ginseng due to some unique less polar ginsenosides that are produced during heat-treatment. Although ginseng leaf contains abundant ginsenosides, attention has mostly focused on ginseng root; relatively few publications have focused on ginseng leaf. Raw ginseng leaf was steamed nine times to make black ginseng leaf using a process that is similar to that used to produce black ginseng root. Sixteen ginsenosides were analyzed during each steaming while using high-performance liquid chromatography (HPLC). The contents of ginsenosides Rd and Re decreased and the less polar ginsenosides (F2, Rg3, Rk2, Rk3, Rh3, Rh4, and protopanaxatriol) enriched during steam treatment. After nine cycles of steaming, the contents of the less polar ginsenosides F2, Rg3, and Rk2 increased by 12.9-fold, 8.6-fold, and 2.6-fold, respectively. Further, we found that the polar protopanaxadiol (PPD) -type ginsenosides are more likely to be converted from ginsenoside Rg3 to ginsenosides Rk1 and Rg5 via dehydration from Rg3, and from ginsenoside Rh2 to ginsenosides Rk2 and Rh3 through losing an H2O molecule than to be completely degraded to the aglycones PPD during the heat process. This study suggests that ginseng leaves can be used to produce less polar ginsenosides through heat processes, such as steaming.
Project description:Background:Ginsenosides are the unique and bioactive components in ginseng. Ginsenosides are affected by the growing environment and conditions. In New Zealand (NZ), Panax ginseng Meyer (P. ginseng) is grown as a secondary crop under a pine tree canopy with an open-field forest environment. There is no thorough analysis reported about NZ-grown ginseng. Methods:Ginsenosides from NZ-grown P. ginseng in different parts (main root, fine root, rhizome, stem, and leaf) with different ages (6, 12, 13, and 14 years) were extracted by ultrasonic extraction and characterized by Liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Twenty-one ginsenosides in these samples were accurately quantified and relatively quantified with 13 ginsenoside standards. Results:All compounds were separated in 40 min, and a total of 102 ginsenosides were identified by matching MS spectra data with 23 standard references or published known ginsenosides from P. ginseng. The quantitative results showed that the total content of ginsenosides in various parts of P. ginseng varied, which was not obviously dependent on age. In the underground parts, the 13-year-old ginseng root contained more abundant ginsenosides among tested ginseng samples, whereas in the aboveground parts, the greatest amount of ginsenosides was from the 14-year-old sample. In addition, the amount of ginsenosides is higher in the leaf and fine root and much lower in the stem than in the other parts of P. ginseng. Conclusion:This study provides the first-ever comprehensive report on NZ-grown wild simulated P. ginseng.
Project description:Background:Ginseng (Panax ginseng Meyer) is an invaluable medicinal plant containing various bioactive metabolites (e.g., ginsenosides). Owing to its long cultivation period, ginseng is vulnerable to various biotic constraints. Biological control using endophytes is an important alternative to chemical control. Methods:In this study, endophytic Trichoderma citrinoviride PG87, isolated from mountain-cultivated ginseng, was evaluated for biocontrol activity against six major ginseng pathogens. T. citrinoviride exhibited antagonistic activity with mycoparasitism against all ginseng pathogens, with high endo-1,4-β-D-glucanase activity. Results:T. citrinoviride inoculation significantly reduced the disease symptoms caused by Botrytis cinerea and Cylindrocarpon destructans and induced ginsenoside biosynthesis in ginseng plants. T. citrinoviride was formulated as dustable powder and granules. The formulated agents also exhibited significant biocontrol activity and induced ginsenosides production in the controlled environment and mountain area. Conclusion:Our results revealed that T. citrinoviride has great potential as a biological control agent and elicitor of ginsenoside production.
Project description:(1) Background: Panax ginseng root is one of the most important herbal products, and the profiling of ginsenosides is critical for the quality control of ginseng roots at different ages in the herbal markets. Furthermore, interest in assessing the contents as well as the localization of biological compounds has been growing. The objective of this study is to carry out the mass spectrometry (MS)-based profiling and imaging of ginsenosides to assess ginseng roots at different ages; (2) Methods: Optimal ultra performance liquid chromatography coupled to quadrupole time of flight/MS (UPLC-QTOF/MS) was used to profile various ginsenosides from P. ginseng roots. Matrix-assisted laser desorption ionization (MALDI)-time of flight (TOF)/MS-based imaging was also optimized to visualize ginsenosides in ginseng roots; (3) Results: UPLC-QTOF/MS was used to profile 30 ginsenosides with high mass accuracy, with an in-house library constructed for the fast and exact identification of ginsenosides. Using this method, the levels of 14 ginsenosides were assessed in P. ginseng roots cultivated for 4, 5, and 6 years. The optimal MALDI-imaging MS (IMS) was also applied to visualize the 14 ginsenosides in ginseng roots. As a result, the MSI cross sections showed the localization of 4 ginsenoside ions ([M + K]?) in P. ginseng roots at different ages; (4) Conclusions: The contents and localization of various ginsenosides differ depending on the cultivation years of P. ginseng roots. Furthermore, this study demonstrated the utility of MS-based profiling and imaging of ginsenosides for the quality control of ginseng roots.
Project description:<h4>Background</h4><i>Panax ginseng</i> Meyer is cultivated because of its medicinal effects on the immune system, blood pressure, and cancer. Major ginsenosides in fresh ginseng are converted to minor ginsenosides by structural changes such as hydrolysis and dehydration. The transformed ginsenosides are generally more bioavailable and bioactive than the primary ginsenosides. Therefore, in this study, hydrothermal processing was applied to ginseng preparation to increase the yields of the transformed ginsenosides, such as 20(S)-Rg3, Rk1, and Rg5, and enhance antioxidant activities in an effective way.<h4>Methods</h4>Ginseng extract was hydrothermally processed using batch reactors at 100-160°C with differing reaction times. Quantitative analysis of the ginsenoside yields was performed using HPLC, and the antioxidant activity was qualitatively analyzed by evaluating 2,2'-azino-bis radical cation scavenging, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, and phenolic antioxidants. Red ginseng and sun ginseng were prepared by conventional steaming as the control group.<h4>Results</h4>Unlike steaming, the hydrothermal process was performed under homogeneous conditions. Chemical reaction, heat transfer, and mass transfer are generally more efficient in homogeneous reactions. Therefore, maximum yields for the hydrothermal process were 2.5-25 times higher than those for steaming, and the antioxidant activities showed 1.6-4-fold increases for the hydrothermal process. Moreover, the reaction time was decreased from 3 h to 15-35 min using hydrothermal processing.<h4>Conclusion</h4>Therefore, hydrothermal processing offers significant improvements over the conventional steaming process. In particular, at temperatures over 140°C, high yields of the transformed ginsenosides and increased antioxidant activities were obtained in tens of minutes.
Project description:We conducted this study to investigate the beneficial effects of Rhizopus oligosporus fermentation of wild ginseng on ginsenosides, l-carnitine contents and its biological activity. The Rhizopus oligosporus fermentation of wild ginseng was carried out at 30 °C for between 1 and 14 days. Fourteen ginsenosides and l-carnitine were analyzed in the fermented wild ginseng by the ultra high pressure liquid chromatography-mass spectrometry (UPLC-MS) system. Our results showed that the total amount of ginsenosides in ginseng increased from 3,274 to 5,573 mg/kg after 14 days of fermentation. Among the 14 ginsenosides tested, the amounts of 13 ginsenosides (Rg1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg2, Rg3, Rh1, compound K, F1 and F2) increased, whereas ginsenoside Rb1 decreased, during the fermentation. Furthermore, l-carnitine (630 mg/kg) was newly synthesized in fermented ginseng extract after 14 days. In addition, both total phenol contents and DPPH radical scavenging activities showed an increase in the fermented ginseng with respect to non-fermented ginseng. These results show that the fermentation process reduced the cytotoxicity of wild ginseng against RAW264.7 cells. Both wild and fermented wild ginseng showed anti-inflammatory activity via inhibition of nitric oxide synthesis in RAW264.7 murine macrophage cells.
Project description:Heating is a traditional method used in ginseng root processing, however, there aren't reports on differences resulting from baking and steaming. Moreover, ginseng flowers, with 5.06 times more total saponins than ginseng root, are not fully taken advantage of for their ginsenosides. Transformation mechanisms of ginsenosides in ginseng flowers upon baking and steaming were thus explored. HPLC using authentic standards of 20 ginsenosides and UPLC-QTOF-MS/MS were used to quantify and identify ginsenosides, respectively, in ginseng flowers baked or steamed at different temperatures and durations. Results show that baking and steaming caused a 3.2-fold increase in ginsenoside species existed in unheated ginseng flowers (20/64 ginsenosides) and transformation of a certain amount of polar ginsenosides into numerous less polar ginsenosides. Among the 20 ginsenosides with standards, polar ginsenosides were abundant in ginseng flowers baked or steamed at lower temperatures, whereas less polar ginsenosides occurred and were enriched at higher temperatures. Furthermore, the two types of heating treatments could generate mostly similar ginsenosides, but steaming was much efficient than baking in transforming polar- into less polar ginsenosides, with steaming at 120 °C being comparably equivalent to baking at 150 °C. Moreover, both the two heating methods triggered ginsenoside acetylation and thus caused formation of 16 acetylginsenosides. Finally, a new transformation mechanism concerning acetyl-ginsenosides formation was proposed.
Project description:Background:White ginseng consists of the roots and rhizomes of the Panax species, and red ginseng is made by steaming and drying white ginseng. While red ginseng has both polar and nonpolar ginsenosides, previous studies showed white ginseng to have only polar ginsenosides. Because nonpolar ginsenosides are formed through the manufacture of red ginseng from white ginseng, researchers have generally thought that nonpolar ginsenosides do not exist in white ginseng. Methods:We developed a simultaneous quantitative method for six nonpolar ginsenosides in white ginseng using reverse-phase high-performance liquid chromatography coupled with integrated pulsed amperometric detection. The nonpolar ginsenosides of white ginseng were extracted for 4 h under reflux with 50% methanol. Results:Using the gradient elution system, all target components were completely separated within 50 min. Nonpolar ginsenosides were determined in the rhizome head (RH), main root (MR), lateral root, and hairy root (HR) of 6-year-old white ginseng samples obtained from several regions (Geumsan, Punggi, and Kanghwa). The total content in the HR of white ginseng was 37.8-56.8% of that in the HR of red ginseng. The total content in the MR of white ginseng was 5.9-24.3% of that in the MR of red ginseng. In addition, the total content in the RH of white ginseng was 28.5-35.8% of that in the HR of red ginseng. Conclusion:It was confirmed that nonpolar ginsenosides known to be specific components of red ginseng were present at substantial concentrations in the HR or RH of white ginseng.