• Journal of Microbiology and Biotechnology
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• v.27 no.7
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• pp.1233-1241
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• 2017

The ginsenoside Rh2 has strong anti-cancer, anti-inflammatory, and anti-diabetic effects. However, the application of ginsenoside Rh2 is restricted because of the small amounts found in Korean white and red ginsengs. To enhance the production of ginsenoside Rh2-MIX (comprising 20(S)-Rh2, 20(R)-Rh2, Rk2, and Rh3 as a 10-g unit) with high specificity, yield, and purity, a new combination of enzymatic conversion using the commercial enzyme Viscozyme L followed by acid treatment was developed. Viscozyme L treatment at pH 5.0 and $50^{\circ}C$ was used initially to transform the major ginsenosides Rb1, Rb2, Rc, and Rd into ginsenoside F2, followed by acid-heat treatment using citric acid 2% (w/v) at pH 2.0 and $121^{\circ}C$ for 15 min. Scale-up production in a 10-L jar fermenter, using 60 g of the protopanaxadiol-type ginsenoside mixture from ginseng roots, produced 24 g of ginsenoside Rh2-MIX. Using 2 g of Rh2-MIX, 131 mg of 20(S)-Rh2, 58 mg of 20(R)-Rh2, 47 mg of Rk2, and 26 mg of Rh3 were obtained at over 98% chromatographic purity. Then, the anti-cancer effect of the four purified ginsenosides was investigated on B16F10, MDA-MB-231, and HuH-7 cell lines. As a result, these four rare ginsenosides markedly inhibited the growth of the cancer cell lines. These results suggested that rare ginsenoside Rh2-MIX could be exploited to prepare an anti-cancer supplement in the functional food and pharmaceutical industries.

• Journal of Ginseng Research
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• v.37 no.1
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• pp.124-134
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• 2013

The authentication of the physico-chemical properties of ginsenosides reference materials as well as qualitative and quantitative batch analytical data based on validated analytical procedures is a prerequisite for certifying good manufacturing practice (GMP). Ginsenoside Rb1 and Rg1, representing protopanaxadiol and protopanaxatriol ginsenosides, respectively, are accepted as marker substances in quality control standards worldwide. However, the current analytical methods for these two compounds recommended by Korean, Chinese, European, and Japanese pharmacopoeia do not apply to red ginseng preparations, particularly the extract, because of the relatively low content of the two agents in red ginseng compared to white ginseng. In manufacturing fresh ginseng into red ginseng products, ginseng roots are exposed to a high temperature for many hours, and the naturally occurring ginsenoside Rb1 and Rg1 are converted to artifact ginsenosides such as Rg3, Rg5, Rh1, and Rh2 during the heating process. The analysis of ginsenosides in commercially available ginseng products in Korea led us to propose the inclusion of the (20S)- and (20R)-ginsenoside Rg3, including ginsenoside Rb1 and Rg1, as additional reference materials for ginseng preparations. (20S)- and (20R)-ginsenoside Rg3 were isolated by Diaion HP-20 adsorption chromatography, silica gel flash chromatography, recrystallization, and preparative HPLC. HPLC fractions corresponding to those two ginsenosides were recrystallized in appropriate solvents for the analysis of physico-chemical properties. Documentation of those isolated ginsenosides was achieved according to the method proposed by Gaedcke and Steinhoff. The ginsenosides were subjected to analyses of their general characteristics, identification, purity, content quantification, and mass balance tests. The isolated ginsenosides showed 100% purity when determined by the three HPLC systems. Also, the water content was found to be 0.534% for (20S)-Rg3 and 0.920% for (20R)-Rg3, meaning that the net mass balances for (20S)-Rg3 and (20R)-Rg3 were 99.466% and 99.080%, respectively. From these results, we could assess and propose a full spectrum of physico-chemical properties of (20S)- and (20R)-ginsenoside Rg3 as standard reference materials for GMP-based quality control.

• Korean Journal of Food Science and Technology
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• v.35 no.3
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• pp.536-539
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• 2003

Commercial white and red ginseng concentrates were analysed for total ginsenoside contents, and compositions of ginsenosides $Rb_1,\;Rb_2,\;Rc,\;Re,\;Rf,\;Rg_1,\;20(S)\;Rg_3,\;20(S)\;Rh_1,\;and\;20(R)\;Rh_1$. The content of crude saponin and total ginsenosides of white ginseng concentrates (WGC) were about 2-3 times higher than those of red ginseng concentrates (RGC). HPLC showed that each ginsenoside content was higher in WGC, with those of $Rb_1,\;Rg_1,\;and\;Rb_2$ being over three times higher than that of RGC. 20(S)- and 20(R)-ginsenoside $Rg_3$, specific artifacts found only in red ginseng, were detected both in WGC and RGC by HPLC. differences in the contents of these specific ginsenosides between WGC and RGC were not significant. The contents of 20(S)-ginsenoside $Rg_1$, determined by HPLC were 0.40 and 0.53 in WGC, whereas 0.48% and 0.47%, and those of 20(R)-ginsenoside $Rg_3$, were 0.14 and 0.22% in WGC, and 0.10 and 0.11% in RGC using the methods of shibata and food Code, respectively.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.115-126
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• 1998

Four new dammarnae-glycosides named ginsenosides Rgs, Rh4, RsB and Rf2 have been isolated 1'rom Korean red ginseng, the root of Panax ginseng C. A. Meyer (Araliaceae) and their chemical structures have been elucidated by chemical and spectroscopic methods, including'H-'H COSY, HMQC, HMBC, NOESY, as 3-0- [$\beta$-D-glucopyranosyl(1 ~2)-$\beta$-D-glucopyranosyl] dammar-20(22) , B4-diene-3P,12P-diol (ginsenoside Rgs),6-0-$\beta$-D-glucopyranosyl-dammar-20(22),24-diene-3P,6P, 12P-triol (ginsenoside Rh4),3-0- [6" -0-acetyl-D-glucopyranosyl(1 ~2)--D-glucopyranosyl] 20(5)- protopanaxadiol (ginsenoside Rs3) and 6-0- [u-L-rhamno-pyranosyl(1 ~2)-$\beta$-D-glucopyranosyl] dammarane -3$\beta$, 6a, 12 $\beta$, 20(R),25-pentol(ginsenoslde Rfa). The absolute stereo structure of a double bond at C-20(22) was determined as entgegen type by applying NOESY.OESY.

• Natural Product Sciences
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• v.21 no.2
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• pp.111-121
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• 2015

The root of Panax ginseng, is a Korea traditional medicine, which is used in both raw and processed forms due to their different pharmacological activities. As part of a continued chemical investigation of ginseng, the focus of this research is on the isolation and identification of compounds from Panax ginseng root by open column chromatography, medium pressure liquid chromatography, semi-preparative-high performance liquid chromatography, Fast atom bombardment mass spectrometric, and nuclear magnetic resonance. Dammarane-type triterpenoid saponins were isolated from Panax ginseng root by open column chromatography, medium pressure liquid chromatography, and semi-preparative-high performance liquid chromatography. Their structures were identified as protopanaxadiol ginsenosides [gypenoside-V (1), ginsenosides-Rb1 (2), -Rb2 (3), -Rb3 (4), -Rc (5), and -Rd (6)], protopanaxatriol ginsenosides [20(S)-notoginsenoside-R2 (7), notoginsenoside-Rt (8), 20(S)-O-glucoginsenoside-Rf (9), 6-O-[$\alpha$-L-rhamnopyranosyl(1$\rightarrow$2-$\beta$-D-glucopyranosyl]-20-O-$\beta$-D-glucopyranosyl-$3\beta$,$12\beta$, 20(S)-dihydroxy-dammar-25-en-24-one (10), majoroside-F6 (11), pseudoginsenoside-Rt3 (12), ginsenosides-Re (13), -Re5 (14), -Rf (15), -Rg1 (16), -Rg2 (17), and -Rh1 (18), and vinaginsenoside-R15 (19)], and oleanene ginsenosides [calenduloside-B (20) and ginsenoside-Ro (21)] through the interpretation of spectroscopic analysis. The configuration of the sugar linkages in each saponin was established on the basic of chemical and spectroscopic data. Among them, compounds 1, 8, 10, 11, 12, 19, and 20 were isolated for the first time from P. ginseng root.

• Korean Journal of Medicinal Crop Science
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• v.21 no.5
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• pp.401-414
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• 2013

Ginsenoside Rg3 (G-Rg3) contained only in red ginseng has been found to show various pharmacological effects such as an anticancer, antiangiogenetic, antimetastastic, liver protective, neuroprotective immunomodulating, vasorelaxative, antidiabetic, insulin secretion promoting and antioxidant activities. It is well known that G-Rg3 could be divided into 20(R)-Rg3 and 20(S)-Rg3 according to the hydroxyl group attached to C-20 of aglycone, whose structural characteristics show different pharmacological activities. It has been reported that G-Rg3 is metabolized to G-Rh2 and protopanaxadiol by the conditions of the gastric acid or intestinal bacteria, thereby these metabolites could be absorbed, suggesting its absolute bioavailability (2.63%) to be very low. Therefore, we reviewed the chemical, physical and biological transformation methods for the production on a large scale of G-Rg3 with various pharmacological effects. We also examined the influence of acid and heat treatment-induced potentials on for the preparation method of higher G-Rg3 content in ginseng and ginseng products. Futhermore, the microbial and enzymatic bio-conversion technologies could be more efficient in terms of high selectivity, efficiency and productivity. The present review discusses the available technologies for G-Rg3 production on a large scale using chemical and biological transformation.

• Journal of Ginseng Research
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• v.35 no.3
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• pp.375-383
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• 2011

In the previous report, we have demonstrated that ginsenoside Rc, one of major ginsenosides, is a major component for the restoration for normal growth of worms in cholesterol-deprived medium. In the present study, we further investigated the roles of minor ginsenosides, such as ginsenoside $Rh_1$ and $Rh_2$, ginsenoside metabolites such as compound K (CK), protopanaxadiol (PPD), and protopanaxatriol (PPT) and ginsenoside epimers such as 20(R)- and 20(S)-ginsenoside $Rg_3$ in cholesterol-deprived medium. We found that ginsenoside $Rh_1$ almost restored normal growth of worms in cholesterol-deprived medium in F1 generation. However, supplement of ginsenoside $Rh_2$ caused a suppression of worm growths in cholesterol-deprived medium. In addition, CK and PPD also slightly restored normal growth of worms in cholesterol-deprived medium but PPT not. In experiments using ginsenoside epimers, supplement of 20(S)- but not 20(R)-ginsenoside $Rg_3$ in cholesterol-deprived medium also almost restored worm growth. These results indicate that the absence or presence of carbohydrate component at backbone of ginsenoside, the number of carbohydrate attached at carbon-3, and the position of hydroxyl group at carbon-20 of ginsenoside might plays important roles in restoration of worm growth in cholesterol-deprived medium.

• Journal of Ginseng Research
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• v.44 no.4
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• pp.611-618
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• 2020

Background: It is well recognized that gut microbiota is involved in the biotransformation of ginsenosides by converting the polar ginsenosides to nonpolar bioactive ginsenosides. However, the roles of the gut microbiota on the pharmacokinetics of ginsenosides in humans have not yet been fully elucidated. Methods: Red ginseng (RG) or fermented red ginseng was orally administered to 34 healthy Korean volunteers, and the serum concentrations of the ginsenosides were determined using liquid chromatography-tandem mass spectrometry. In addition, the fecal ginsenoside Rd- and compound K (CK)eforming activities were measured. Then, the correlations between the pharmacokinetic profiles of the ginsenosides and the fecal ginsenoside-metabolizing activities were investigated. Results: For the RG group, the area under the serum concentratione-time curve values of ginsenosides Rd, F2, Rg3, and CK were 8.20 ± 11.95 ng·h/mL, 4.54 ± 3.70 ng·h/mL, 36.40 ± 19.68 ng·h/mL, and 40.30 ± 29.83 ng·h/mL, respectively. For the fermented red ginseng group, the the area under curve from zero to infinity (AUC_∞) values of ginsenosides Rd, F2, Rg3, and CK were 187.90 ± 95.87 ng·h/mL, 30.24 ± 41.87 ng·h/mL, 28.68 ± 14.27 ng·h/mL, and 137.01 ± 96.16 ng·h/mL, respectively. The fecal CK-forming activities of the healthy volunteers were generally proportional to their ginsenoside Rd-eforming activities. The area under the serum concentration-time curve value of CK exhibited an obvious positive correlation (r = 0.566, p < 0.01) with the fecal CK-forming activity. Conclusion: The gut microbiota may play an important role in the bioavailability of the nonpolar RG ginsenosides by affecting the biotransformation of the ginsenosides.

• Journal of Ginseng Research
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• v.20 no.4
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• pp.389-415
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• 1996

Panax ginseng C.A. Meyer(Araliaceae) has been traditionally used as an expensive and precious medicine in oriental countries for more than 5, 000 years. Ginseng saponin isolated from the root of Panax ginseng have been regarded as the main effective components responsible for the pharmacological and biological activities. Such as antiaging effects. antidiabetic effects anticancer effects. Protection against physical and chemical stress. Analgesic and antipyretic effects. Effects on the central nervous system, tranquilizing action and others. Thirty kinds of ginsenosides have been so far isolated from ginseng saponin and their chemical structures have been elucidated since 1960's. Among which protopanaxadiol type is 19 kinds. protopanaxatriol type. 10 kinds and oleanane type, one. Since ginsenosides are generally labile under acidic conditions ordinary acid hydrolysis is always accompanied by many side reactions, such as epimerization. hydroxylation and cyclization of side chain of the sapogenins Especially. it is well known that C-20 glycosyl linkage of ginsenoside was hydrolysed on heating with acetic acid to give an equilibrated mixture of 20(S) and 20(R) epimers. And also, the chemical transformations of the secondary metabolites have appeared during the steaming process to prepare red ginseng. Indicating demalonylation of malonyl ginsenosides, elimination of glycosyl residue at C-20 and isomerization of hydroxyl configuration at C-20. But these studies have not provided a comprehensive picture in explaning how these ginsenosides showed val'iotas pharmacological activities of ginseng. Though some of them have been involved in the mechanism of pharmacological actions. Recently, non-saponin components have received a great deal of attention for their antioxidant, anticancer antidiabetic, immunomodulating. anticomplementary activities and so on. To meet the demand for such wide applications, studies on the non-saponin components play an important role in providing a good evidence of pharmacological and biol ogical activities. Among the non-saponin constituents of Korean ginseng, polyacetylenes, phenols. Sesquiterpenes, alkaloids. polysaccharides oligosaccharides, oligopeptides and aminoglycosides together with ginsenosides of terrestrial part are mainly described.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.255-264
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• 2023

Background: Red ginseng (RG) alleviates psychiatric disorders. Fermented red ginseng (fRG) alleviates stress-induced gut inflammation. Gut dysbiosis causes psychiatric disorders with gut inflammation. To understand the gut microbiota-mediated action mechanism of RG and fRG against anxiety/depression (AD), we investigated the effects of RG, fRG, ginsenoside Rd, and 20(S)-β-D-glucopyranosyl protopanaxadiol (CK) on gut microbiota dysbiosis-induced AD and colitis in mice. Methods: Mice with AD and colitis were prepared by exposing to immobilization stress (IS) or transplanting the feces of patients with ulcerative colitis and depression (UCDF). AD-like behaviors were measured in the elevated plus maze, light/dark transition, forced swimming, and tail suspension tests. Results: Oral gavage of UCDF increased AD-like behaviors and induced neuroinflammation, gastrointestinal inflammation, and gut microbiota fluctuation in mice. Oral administration of fRG or RG treatment reduced UCDF-induced AD-like behaviors, hippocampal and hypothalamic IL-6 expression, and blood corticosterone level, whereas UCDF-suppressed hippocampal BDNF⁺NeuN⁺ cell population and dopamine and hypothalamic serotonin levels increased. Furthermore, their treatments suppressed UCDF-induced colonic inflammation and partially restored UCDF-induced gut microbiota fluctuation. Oral administration of fRG, RG, Rd, or CK also decreased IS-induced AD-like behaviors, blood IL-6 and corticosterone and colonic IL-6 and TNF-α levels, and gut dysbiosis, while IS-suppressed hypothalamic dopamine and serotonin levels increased. Conclusion: Oral gavage of UCDF caused AD, neuroinflammation, and gastrointestinal inflammation in mice. fRG mitigated AD and colitis in UCDF-exposed mice by the regulation of the microbiota-gut-brain axis and IS-exposed mice by the regulation of the hypothalamic-pituitary-adrenal axis.