Compound K (C-K), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. Here, we describe a novel therapeutic role for C-K in the treatment of lethal sepsis through the modulation of Toll-like receptor (TLR) 4-associated signalling via glucocorticoid receptor (GR) binding. In mononuclear phagocytes, C-K significantly repressed the activation of TLR4/lipopolysaccharide (LPS)-induced NF-κB and mitogen-activated protein kinases (MAPKs), as well as the secretion of pro-inflammatory cytokines. However C-K did not affect the TLR3-mediated expression of interferon-β or the nuclear translocation of IRF-3. C-K competed with the synthetic glucocorticoid dexamethasone for binding to GR and activated glucocorticoid responsive element (GRE)-containing reporter plasmids in a dose-dependent manner. In addition, the blockade of GR with either the GR antagonist RU486 or a siRNA against GR substantially reversed the anti-inflammatory effects of C-K. Furthermore, TLR4-dependent repression of inflammatory response genes by C-K was mediated through the disruption of p65/interferon regulatory factor complexes. Importantly, pre- or post-treatment with C-K significantly rescued mice from Gram-negative bacterial LPS-induced lethal shock by lowering their systemic inflammatory cytokine levels and by reversing the lethal sequelae of sepsis. Collectively, these results demonstrate that C-K, as a functional ligand of GR, regulates distinct TLR4-mediated inflammatory responses, and suggest a novel therapy for Gram-negative septic shock.
A quick and simple method for simultaneous determination of the 30 ginsenosides (ginsenoside Ro, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, 20(S)-Rg2, 20(R)-Rg2, 20(S)-Rg3, 20(R)-Rg3, 20(S)-Rh1, 20(S)-Rh2, 20(R)-Rh2, F1, F2, F4, Ra1, Rg6, Rh4, Rk3, Rg5, Rk1, Rb3, Rk2, Rh3, compound Y, compound K, and notoginsenoside R1) in Panax ginseng preparations was developed and validated by an ultra performance liquid chromatography photo diode array detector. The separation of the 30 ginsenosides was efficiently undertaken on the Acquity BEH C-18 column with gradient elution with phosphoric acids. Especially the chromatogram of the ginsenoside Ro was dramatically enhanced by adding phosphoric acid. Under optimized conditions, the detection limits were 0.4 to 1.7 mg/L and the calibration curves of the peak areas for the 30 ginsenosides were linear over three orders of magnitude with a correlation coefficients greater than 0.999. The accuracy of the method was tested by a recovery measurement of the spiked samples which yielded good results of 89% to 118%. From these overall results, the proposed method may be helpful in the development and quality of P. ginseng preparations because of its wide range of applications due to the simultaneous analysis of many kinds of ginsenosides.
The hydrolysis of protopanaxadiol-type saponin mixture by various glycoside hydrolases was examined. Among these enzymes, crude preparations of lactase from Aspergillus oryzae, b b-galactosidase from A. oryzae, and cellulase from Trichoderma viride were found to produce ginsenoside , and Rc to ginsenosides Rd, Rg 3 , and F 2 , and compound K by crude preparations of four glycoside hydrolases were also studied. This is the first report on the enzymatic preparation of an intestinal bacterial metabolite, ginsenoside F 2 , in quantity, and a considerable amount of a minor saponin, ginsenoside Rg 3 , from a protopanaxadiol-type saponin mixture.
BackgroundThe chemical constituents of Panax ginseng are changed by processing methods such as steaming or sun drying. In the present study, the chemical change of Panax ginseng induced by steaming was monitored in situ.MethodsSamples were separated from the same ginseng root by incision during the steaming process, for in situ monitoring. Sampling was sequentially performed in three stages; FG (fresh ginseng) → SG (steamed ginseng) → RG (red ginseng) and 60 samples were prepared and freeze dried. The samples were then analyzed to determine 43 constituents among three stages of P. ginseng.ResultsThe results showed that six malonyl-ginsenoside (Rg1, Rb1, Rb3, Rc, Rd, Rb2) and 15 amino acids were decreased in concentration during the steaming process. In contrast, ginsenoside-Rh1, 20(S)-Rg2, 20(S, R)-Rg3 and Maillard reaction product such as AF (arginine-fructose), AFG (arginine-fructose-glucose), and maltol were newly generated or their concentrations were increased.ConclusionThis study elucidates the dynamic changes in the chemical components of P. ginseng when the steaming process was induced. These results are thought to be helpful for quality control and standardization of herbal drugs using P. ginseng and they also provide a scientific basis for pharmacological research of processed ginseng (Red ginseng).
UV irradiation is the main factor contributing to skin damages that are associated with an excessive production of matrix-degrading metalloproteinase (MMP)-1 and a deficient expression of collagens. To date, red ginseng has been revealed to possess many biomedical effects, such as anti-aging, anti-oxidation, and anti-inflammatory. In this study, we prepared the Korean Red Ginseng extracts treated with enzyme (KRGE) and investigated the effects of dietary KRGE on the formation of wrinkles generated by UVB irradiation in hairless mice. It was found that KRGE inhibited the UVB-induced formation of wrinkles, epidermal thickness, and skin dryness in hairless mice. Further results also showed that KRGE attenuated UVB-induced MMP-1 level, while accelerated procollagen type I, transforming growth factor-β1 secretion. Interestingly, the expression of profilaggrin and filaggrin in both the epidermis and dermis were decreased due to UVB exposure and reversed by KRGE. The KRGE 0.06% was prior to KRGE 0.24%. In view of these results, which indicated that KRGE protected skin from UVB-induced photodamages, which may not only mediated by regulating of MMP-1 and procollagen type I, but also by increasing the production of profilaggrin and filaggrin. In conclusion, our results suggest that KRGE may be a promising agent for the treatment of skin photodamages. The challenge of KRGE will be expected as cosmeceuticals and nutraceuticals in order to intervene in aging-related degenerative skin changes.
Discriminating between two herbal medicines (Panax ginseng and Panax quinquefolius), with similar chemical and physical properties but different therapeutic effects, is a very serious and difficult problem. Differentiation between two processed ginseng genera is even more difficult because the characteristics of their appearance are very similar. An ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS)-based metabolomic technique was applied for the metabolite profiling of 40 processed P. ginseng and processed P. quinquefolius. Currently known biomarkers such as ginsenoside Rf and F11 have been used for the analysis using the UPLC-photodiode array detector. However, this method was not able to fully discriminate between the two processed ginseng genera. Thus, an optimized UPLC-QTOF-based metabolic profiling method was adapted for the analysis and evaluation of two processed ginseng genera. As a result, all known biomarkers were identified by the proposed metabolomics, and additional potential biomarkers were extracted from the huge amounts of global analysis data. Therefore, it is expected that such metabolomics techniques would be widely applied to the ginseng research field.
Panax ginseng C.A. MEYER is one of the most popular medicinal herbs in Asia and the chemical constituents are changed by processing methods such as steaming or sun drying. Metabolomic analysis was performed to distinguish age discrimination of four-and six-year-old red ginseng using ultra-performance liquid chromatography quadruple time of flight mass spectrometry (UPLC-QToF-MS) with multivariate statistical analysis. Principal component analysis (PCA) showed clear discrimination between extracts of red ginseng of different ages and suggest totally six discrimination markers (two for four-year-old and four for six-year-old red ginseng). Among these, one marker was isolated and the structure determined by NMR spectroscopic analysis was 13-cis-docosenamide (marker 6-1) from six-year-old red ginseng. This is the first report of a metabolomic study regarding the age differentiation of red ginseng using UPLC-QToF-MS and determination of the structure of the marker. These results will contribute to the quality control and standardization as well as provide a scientific basis for pharmacological research on red ginseng.Key words Panax ginseng; red ginseng; multivariate analysis; ultra-performance liquid chromatography quadruple time of flight mass spectrometry (UPLC-QToF-MS); metabolomics; 13-cis-docosenamide Korean ginseng (Panax ginseng C.A. MEYER) is one of the most widely used and acclaimed herbs in the world.1-3) Traditionally, the root of P. ginseng, the most used and valuable part, is physically subdivided into three groups; the main root, lateral root, and root hairs.1) It has already been reported that the chemical constituents and efficacy of each part of the ginseng root are quite different.1) It has been processed to make white ginseng (by air-drying the roots after peeling or not peeling) and red ginseng (by steaming the roots at 98-100°C without peeling) to enhance its preservation and efficacy. Red ginseng is more common as an herbal medicine, because steaming induces changes in the chemical constituents and enhances the biological activities of ginseng. 4)P. ginseng is generally cultivated for four or six years in the field before harvest. Thus, four and six year cultivated P. ginseng is a common item in the Korean ginseng market. However, six year cultivated P. ginseng and products thereof (including white ginseng and red ginseng) are produced and consumed much more than others. Because the cultivation age and harvest season have a significant effect on the quality and efficacy of ginseng, products of six year cultivated P. ginseng are also more expensive than products of four year cultivated P. ginseng. Additionally, a low survival rate and higher cultivation costs contribute to the expensive price of six year cultivated P. ginseng. The accurate determination of the cultivation age of ginseng is a very important problem in the market, although the cultivation age of ginseng can hardly be determined by the physical appearance alone, such as by the number of stem vestiges in rhizome. 5)In recent years, ...
BackgroundDuring the aging process, skin shows visible changes, characterized by a loss of elasticity and the appearance of wrinkles due to reduced collagen production and decreased elasticity of elastin fibers. Panax ginseng Meyer has been used as a traditional medicine for various diseases due to its wide range of biological activities including skin protective effects. Ginsenosides are the main components responsible for the biological activities of ginseng. However, the protective activities of an enzymatic preparation of red ginseng against human skin aging have not been investigated.MethodsThe efficacy of an enzyme-treated powder complex of red ginseng (BG11001) in preventing human skin aging was evaluated by oral administration to 78 randomized individuals. All patients were requested to take three daily capsules containing either 750 mg of BG11001 or a placebo vehicle for 24 wk; at the end of the testing period, skin roughness, elasticity, and skin water content were measured.ResultsBG11001 significantly reduced the average roughness of eye wrinkles and the Global Photo Damage Score compared with the placebo, although there were no significant differences in arithmetic roughness average between the groups. In addition, gross elasticity and net elasticity values increased, and transepidermal water loss level decreased, indicating improved skin elasticity and moisture content.ConclusionIn conclusion, enzyme-treated red ginseng extract significantly improved eye wrinkle roughness, skin elasticity, and moisture content. Moreover, enzyme-treated red ginseng extract would be useful substance as a bio-health skin care product.
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