• Archives of Pharmacal Research
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• v.27 no.8
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• pp.834-839
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• 2004

In human neuroblastoma SK-N-BE(2) cells undergoing apoptotic death induced by ginsenos-ide Rh2, a dammarane glycoside that was isolated from Panax ginseng C. A. Meyer, caspase-1 and caspase-3 were activated. The expression of Bax was increased in the cells treated with ginsenoside Rh2, whereas Bcl-2 expression was not altered. Treatment with caspase-1 inhibi-tor, Ac-YVAD-CMK, or caspase-3 inhibitor, Z-DEVD-FMK, partially inhibited ginsenoside Rh2-induced cell death but almost suppressed the cleavage of the 116 kDa PARP into a 85 kDa fragment. When the levels of p53 were examined in this process, p53 accumulated rapidly in the cells treated early with ginsenoside Rh2. These results suggest that activation of caspase-1 and -3 and the up-regulation of Bax are required in order for apoptotic death of SK-N-BE(2) cells to be induced by ginsenoside Rh2, and p53 plays an important role in the pathways to promote apoptosis.

• Journal of Ginseng Research
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• v.34 no.3
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• pp.227-236
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• 2010

The objective of this study was to evaluate the potential use of ginseng leaf as a cosmetic material. In this research, we employed enzymatic treated ginseng leaf by using Ultraflo L to improve the recovery of ginsenosides from the ginseng leaf and studied the biological activities and skin safety of the enzymatic treated ginseng leaf for use as a cosmetic material. The total ginsenoside contents of the non-enzymatic treated ginseng leaf (NEGL) and Ultraflo L treated ginseng leaf (UTGL) were 271 and 406 mg/g, respectively. The level of metabolite ginsenosides (sum of Rg2, Rg3, Rg5, Rk1, compound K, Rh1, Rh2, and F2) was higher in UTGL (93.1 mg) compared to NEGL (62.4 mg) in one gram ginseng leaf extract. The increase in amounts of ginsenoside types in UTGL compared to NEGL was generally 140% to 157%. UTGL exhibited relatively higher 2,2-diphenyl-2-picrylhydrazyl hydrate ($IC_{50}$, 2.8 mg/mL) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt ($IC_{50}$, 1.6 mg/mL) radical scavenging activities compared to NEGL (4.8 mg/mL and 2.2 mg/mL). The UTGL group showed normalized hydrogen peroxide, lipid peroxidation and visual wrinkling grade induced-UVB exposure. The UTGL did not induce any adverse reactions such as erythema and edema on intact skin sites; however, some guinea pigs treated with UTGL on abraded skin sites showed very slight erythema. The primary irritation index (PII) score of UTGL was 0.05 and it was classified as a practically non-irritating material (PII, 0 to 0.5). In skin sensitization tests with guinea pigs, UTGL had a positive rate of skin sensitization at 40%, and the mean evaluation score was 0.4.

• Journal of the Korean Applied Science and Technology
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• v.35 no.4
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• pp.1213-1223
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• 2018

This study was carried out to investigate extraction efficiency by microwave for extraction of pesticide residues and the bioconversion of ginsenosides of ginseng leaf by using various lactic acid bacteria in order to promote the utilization of ginseng leaf. The hexane extraction by microwave of tolclofos-methyl and azoxystrobin in ginseng leaf was efficient. The optimal condition for extraction of tolclofos-methyl and azoxystrobin in ginseng leaf by microwave was 50 to 95 watts of power supply, 3 minutes of extraction.The gisenosides Rg1 and Rb1 contents have decreased, while the Rh1, Rg3, Rk1 and Rh2 have increased due to fermentation. The ginsenosides Rg3 of the fermented ginseng leaf has increased and the contents were $70.62{\sim}77.61{\mu}g/g$(control $2.77{\mu}g/g$). The total phenolic acid content and electron donating ability of the ginseng leaf have totally decreased after 7 days of fermentation. The total phenolic acid contents of the fermented ginseng leaf with various lactic acid bacteria did not show any tendency as different strains.

• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.315-322
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• 2019

Seasonal ginsenoside flux in the leaves of 5-year-old Panax ginseng was analyzed from the field-grown ginseng, for the first time, to study possible biosynthesis and translocation of ginsenosides. The concentrations of nine major ginsenosides, Rg1, Re, Rh1, Rg2, R-Rh1, Rb1, Rc, Rb2, and Rd, were determined by UHPLC during the growth in between April and November. It was confirmed total ginsenoside content in the dried ginseng leaves was much higher than the roots by several folds whereas the composition of ginsenosides was different from the roots. The ginsenoside flux was affected by ginseng growth. It quickly increased to 10.99±0.15 (dry wt%) in April and dropped to 6.41±0.14% in May. Then, it slowly increased to 9.71±0.14% in August and maintained until October. Ginsenoside Re was most abundant in the leaf of P. ginseng, followed by Rd and Rg1. Ginsenosides Rf and Ro were not detected from the leaf. When compared to the previously reported root data, ginsenosides in the leaf appeared to be translocated to the root, especially in the early vegetative stage even though the metabolite translocated cannot be specified. The flux of ginsenoside R-Rh1 was similar to the other (20S)-PPT ginsenosides. When the compositional changes of each ginsenoside in the leaf was analyzed, complementary relationship was observed from ginsenoside Rg1 and Re, as well as from ginsenoside Rd and Rb1+Rc. Accordingly, ginsenoside Re in the leaf was proposed to be synthesized from ginsenoside Rg1. Similarly, ginsenosides Rb1 and Rc were proposed to be synthesized from Rd.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.366-374
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• 2016

Background: In this study, we screened and identified an endophyte JG09 having strong biocatalytic activity for ginsenosides from Platycodon grandiflorum, converted ginseng total saponins and ginsenoside monomers, determined the source of minor ginsenosides and the transformation pathways, and calculated the maximum production of minor ginsenosides for the conversion of ginsenoside Rb1 to assess the transformation activity of endophyte JG09. Methods: The transformation of ginseng total saponins and ginsenoside monomers Rb1, Rb2, Rc, Rd, Rg1 into minor ginsenosides F2, C-K and Rh1 using endophyte JG09 isolated by an organizational separation method and Esculin-R2A agar assay, as well as the identification of transformed products via TLC and HPLC, were evaluated. Endophyte JG09 was identified through DNA sequencing and phylogenetic analysis. Results: A total of 32 ${\beta}$-glucosidase-producing endophytes were screened out among the isolated 69 endophytes from P. grandiflorum. An endophyte bacteria JG09 identified as Luteibacter sp. effectively converted protopanaxadiol-type ginsenosides Rb1, Rb2, Rc, Rd into minor ginsenosides F2 and C-K, and converted protopanaxatriol-type ginsenoside Rg1 into minor ginsenoside Rh1. The transformation pathways of major ginsenosides by endophyte JG09 were as follows: $Rb1{\rightarrow}Rd{\rightarrow}F2{\rightarrow}C-K$; $Rb2{\rightarrow}C-O{\rightarrow}C-Y{\rightarrow}C-K$; $Rc{\rightarrow}C-Mc1{\rightarrow}C-Mc{\rightarrow}C-K$; $Rg1{\rightarrow}Rh1$. The maximum production rate of ginsenosides F2 and C-K reached 94.53% and 66.34%, respectively. Conclusion: This is the first report about conversion of major ginsenosides into minor ginsenosides by fermentation with P. grandiflorum endophytes. The results of the study indicate endophyte JG09 would be a potential microbial source for obtaining minor ginsenosides.

• Korean Journal of Food Science and Technology
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• v.47 no.6
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• pp.757-764
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• 2015

Red ginseng was treated by subcritical water extraction (SWE) whose two parameters were the extraction temperature ($105-150^{\circ}C$) and time (5-20 min) under a high pressure. The oBrix value, solid content, color difference, and turbidity of the red ginseng extract increased with increasing extraction time and temperature, while the pH decreased. The total concentration of ginsenosides in the red ginseng extract was maximal at $120^{\circ}C$ and 20 min. The concentrations of ginsenosides Rg3 and Rh1 were maximal at $150^{\circ}C$ and 15 min. The concentrations of Rg3 and Rh1 were respectively 3.5-5 times and 2-2.5 times higher than those treated by conventional extraction methods with hot water, ethanol, and methanol. SWE is a particularly effective method for the selective extraction of less-polar ginsenosides such as Rg3 which is well known to exert strong anticancer effects.

• Journal of Microbiology and Biotechnology
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• v.23 no.12
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• pp.1802-1805
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• 2013

Ginsenosides are the most important ingredient of ginseng and are known to possess many pharmacological and biological effects. Rb1, a major protopanaxadiol ginsenoside, is the most abundant ginsenoside in Panax ginseng C.A Meyer and can be hydrolyzed into more pharmaceutically potent minor ginsenosides. To identify a microorganism that is capable of converting Rb1 into other ginsenosides, we screened 12 Microbacterium spp., and M. trichothecenolyticum was identified as a likely candidate. M. trichothecenolyticum converted Rb1 into Rd and then into Rh2 based on TLC and HPLC analyses of reaction products. This biotransformation method can be easily applied for mass production of Rd and Rh2 by using Rb1.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.211-217
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• 2011

Panax ginseng CA Meyer, a herb from the Araliaceae, has traditionally been used as a medicinal plant in Asian countries. Ginseng extract fermented by ginsenoside-${\beta}$-glucosidase treatment is enriched in ginsenosides such as Rh2 and Rg3. Here we show that a fermented ginseng extract, BST204, has anti-proliferative and anti-invasive effects on HT-29 human colon cancer cells. Treatment of HT-29 cells with BST204 induced cell cycle arrest at $G_1$ phase without progression to apoptosis. This cell cycle arrest was accompanied by up-regulation of tumor suppressor proteins, p53 and p21$^{WAF1/Cip1}$, down-regulation of the cyclin-dependent kinase/cyclins, Cdk2, cyclin E, and cyclin D1 involved in $G_1$ or $G_1/S$ transition, and decrease in the phosphorylated form of retinoblastoma protein. In addition, BST204 suppressed the migration of HT-29 cells induced by 12-O-tetradecanoylphorbol-13-acetate, which correlated with the inhibition of metalloproteinase-9 activity and extracellular signal-regulated kinase activity. The effects of BST204 on the proliferation and the invasiveness of HT-29 cells were similar to those of Rh2. Taken together, the results suggest that fermentation of ginseng extract with ginsenoside-${\beta}$-glucosidase enhanced the anti-proliferative and the anti-invasive activity against human colon cancer cells and these anti-tumor effects of BST204 might be mediated in part by enriched Rh2.

• Journal of Ginseng Research
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• v.33 no.4
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• pp.324-329
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• 2009

Cell-cell adhesion managed by various adhesion molecules is known to be one of pathophysiological phenomena found in numerous immunological diseases such as rheumatoid arthritis and allergic diseases. In this study, we examined the regulatory role of ginsenosides (G)- Rh1, reported to display anti-inflammatory and anti-allergic effects, on CD29-mediated cell adhesion. G-Rh1 significantly suppressed U937 cell-cell adhesion mediated by CD29 but not CD43. It also blocked U937 cell-fibronectin adhesion, mediated by activated CD29, up to 30%. In agreement, this compound also significantly decreased the surface level of CD29 but not CD43 as well as other costimulatory molecules such as CD69, CD80, and CD86. Therefore, these results suggest that G-Rh1 may have inhibitory function on CD29-mediated cell adhesion events, probably contributing to its anti-inflammatory and anti-allergic activities.

• Biotechnology and Bioprocess Engineering:BBE
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• v.11 no.5
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• pp.442-448
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• 2006

Human lactoferrin (hLf) is an iron-binding glycoprotein that has been considered to play many biological roles in the human, including the stimulation of the immune system, antimicrobial and anti-inflammatory effects, and regulation of iron absorption. We generated transgenic Siberian ginseng (Acanthopanax senticosus) cell cultures producing a functional hLf protein using the signal peptide sequence from the endoplasmic reticulum and driven by an oxidative stress-inducible SWPA2 promoter which is highly expressed in plant cell cultures. The production of hLf increased proportionally to cell growth and showed a maximal level (up to 3.6% of total soluble protein) at the stationary phase in suspension cultures. Full-length hLf protein was identified by immunoblot analysis in transgenic cell cultures of Siberian ginseng. Recombinant hLf (rhLf) was purified from suspension cells of Siberian ginseng by ammonium sulfate precipitation, cation-exchange and gel filtration chromatography. N-terminal sequences of rhLf were identical to native hLf (nhLf). The overall monosaccharide composition of rhLf showed the presence of plant specific xylose while sialic acid is absent. Antibacterial activity of purified rhLf was higher than that of nhLf. Taken together, we anticipate that medicinal Siberian ginseng cultured cells, as demonstrated by this study, will be a biotechnologically useful source for commercial production of functional hLf not requiring further purification.