Sang Yoon Choi

Ginsenoside Rh2 induces cell cycle arrest and differentiation in human leukemia cells by upregulating TGF-β expression

The triterpene saponin ginsenoside Rh2 has been shown to have antiproliferative effects on various cancer cells. However, the effect of Rh2 on the cell cycle and its underlying molecular mechanism in human leukemia cells are not fully understood. In this study, we found that Rh2 inhibited the proliferation of human leukemia cells concentration- and time-dependently with an IC(50) of ~38 µM. DNA flow cytometric analysis indicated that Rh2 blocked cell cycle progression at the G(1) phase in HL-60 and U937 cells, and this was found to be accompanied by the downregulations of cyclin-dependent kinase (CDK) 4, CDK6, cyclin D1, cyclin D2, cyclin D3 and cyclin E at the protein level. However, CDK inhibitors (CDKIs), such as p21(CIP1/WAF1) and p27(KIP1), were gradually upregulated after Rh2 treatment at the protein and messenger RNA (mRNA) levels. In addition, Rh2 markedly enhanced the bindings of p21(CIP1/WAF1) and p27(KIP1) to CDK2, CDK4 and CDK6, and these bindings reduced CDK2, CDK4 and CDK6 activities. Furthermore, Rh2 induced the differentiation of HL-60 cells as demonstrated by biochemical assays and the expression levels of cell surface antigens. In addition, treatment of HL-60 cells with Rh2 significantly increased transforming growth factor-β (TGF-β) production, and cotreatment with TGF-β neutralizing antibody prevented the Rh2-induced downregulations of CDK4 and CDK6, upregulations of p21(CIP1/WAF1) and p27(KIP1) levels and the induction of differentiation. These results demonstrate that the Rh2-mediated G(1) arrest and the differentiation are closely linked to the regulation of TGF-β production in human leukemia cells.

Isolation and Anti-Inflammatory Activity of Bakuchiol from Ulmus davidiana var. japonica

The bark of the root and stem of Ulmus davidiana var. japonica has been used as a traditional Korean medicine to treat inflammatory disorders. This plant reportedly exhibits antioxidant, anticancer, and anti-inflammatory effects. A search for biologically active compounds in U. davidiana var. japonica extracts yielded bakuchiol, which we structurally identified on the basis of spectral data, including two-dimensional nuclear magnetic resonance spectroscopy and distortionless enhancement by polarization transfer. In our study, bakuchiol (50 microM) inhibited lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production in RAW 264.7 macrophages by 53.7% and 84.2%, respectively. These results suggested that bakuchiol is one of the potent anti-inflammatory components of U. davidiana var. japonica.

The Changes of Ginsenoside Patterns in Red Ginseng Processed by Organic Acid Impregnation Pretreatment

In order to enhance bioactive functionalities of ginseng, an acid impregnation processing was applied as a pre-treatment in producing red ginseng. Acid impregnation studies were conducted, and acids (ascorbic, malic, and citric acid) were selected. The optimal concentration of each acid was investigated in this study in terms of ginsenoside contents. The most concerned ginsenoside, Rg3 was increased by ascorbic, malic, and citric acid pre-treated red ginseng up to 1 M acid concentration. In the case of ascorbic acid pre-treated red ginseng, Rg2 concentration was increased depending on acid concentrations. Citric acid pre-treatment enhanced Rg2, Rg3, and Rh1+Rh2 formation in red ginseng. Therefore, ginsenoside patterns in red ginseng could be changed by acid impregnation pre-treatment depending on acid concentration and acid types. This research is expected to contribute to the development of the ginseng industry via new red ginseng products with selective and intensified functionality.

Identification of a potent and noncytotoxic inhibitor of melanin production

On the basis of a hit from random screening, biaryl amide derivatives were prepared in a combinatorial manner via parallel solution-phase synthesis, and their effects on melanocytes were investigated to discover new effective skin depigmenting agents. Among the 120 derivatives prepared, five members exhibited a >30% reduction of melanin production at 30 microM with a cell viability of >90%. In particular, compound A(3)/B(5) exhibited effective inhibitory activity on melanin synthesis. Although the inhibition percentage of A(3)/B(5) was slightly lower than that of the positive reference compound, phenylthiourea (PTU), A(3)/B(5) demonstrated a much better cell viability than PTU. In vivo evaluation of A(3)/B(5) also showed a significant decrease of melanin pigments. In addition, the in silico classification model was built based on the experimental data of library members. Our results suggest that these biaryl amide derivatives may act as potent skin depigmenting agents.

Comparison of Ginsenoside and Phenolic Ingredient Contents in Hydroponically-cultivated Ginseng Leaves, Fruits, and Roots

In this study, hydroponically-cultivated ginseng leaves, fruits, and roots were respectively extracted with ethanol. The contents of 12 ginsenosides and three phenolics in the extracts were quantitatively analyzed and the free radical scavenging activities were measured and compared. Hydroponically-cultivated ginseng leaves contained higher levels of gensenosides (Rg1, Rg2+Rh1, Rd, and Rg3) and p-coumaric acid than the other parts of the ginseng plants. The 2,2’-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid radical scavenging activities of leaves were also the highest. Accordingly, hydroponically-grown ginseng leaves were shown to hold promise for use as an environmentally-friendly natural anti-oxidant.

Influence of ginsenoside Rb1 on brain neurosteroid during acute immobilization stress

This study examined whether or not acute stress is linked to increases in the neurosteroid levels, which is a well-known neurotransmitters associated with stress stimuli. The ginsenoside, Rb1, was tested in order to better understand its potential effects on altering the neurosteroid levels and ultimately attenuating stress. The optimal stressed condition was checked by measuring the 5a-dihydroprogesterone (DHP) and allopregnanolone (THP) levels in the brain after immobilization stress at various times. Based on this result, an acute stress model was set up to give 30 min of immobilization stress. The DHP and THP brain levels of the stressed mice were then investigated after administering Rb1 orally (10 mg/kg). These results were compared with the neurosteroid level in the stressed mice not given Rb1. Saline was administered orally to the nonstressed mice to check the placebo effect. Acute immobilization stress induced an increase in the THP and DHP concentration in the frontal cortex and cerebellum. When Rb1 was administered orally prior to immobilization stress, the THP level in the frontal cortex and cerebellum was significantly lower than that in the stressed animals not given Rb1. On the other hand, the DHP level was lower in the cerebellum only. This suggests that the metabolism of the brain neurosteroids in linked to psychological stress, and Rb1 attenuates the stress-induced increase in neurosteroids.

Bioconversion of isoflavones during the fermentation of Samso-Eum with Lactobacillus strains

In this study, the possible application of Lactobacillus strains as a functional starter culture to ferment Samso-Eum (SE), an oriental herbal medicine formula, and the production of bioactive isoflavones (daidzein, genistein) were investigated. Four strains of Lactobacillus (Lactobacillus plantarum KFRI 144, L. amylophilus KFRI 161, L. curvatus KFRI 166, and L. bulgaricus KFRI 344) were used for SE fermentation. Declines in pH and in viable cell counts during fermentation were investigated and the quantification of isoflavones using HPLC were performed after fermentation at 37°C for 48 h. All the tested Lactobacillus strains lowered the pH level to approximately 3.6 after 48 h and showed the highest level of growth at 24 h during SE fermentation. During the SE fermentation of the four Lactobacillus strains, the conversion of isoflavone glycosides (daidzin, genistin) into bioactive aglycones (daidzein, genistein) was observed in all of the fermentations, but with different rates depending on the strains. L. plantarum KFRI 144 and L. amylophilus KFRI 161 exhibited the highest bioconversion rate of isoflavone glycosides into their bioactive aglycones. These results demonstrate that L. plantarum KFRI 144 and L. amylophilus KFRI 161 have potentials as functional starter cultures for manufacturing fermented SE with higher isoflavone bioavailability.

Characteristic study on the chemical components of Korean curved ginseng products

Dried ginseng (DG) is in fact the representing ginseng product in the worldwide market. Although it is made in various packages depending on the processing method, size and age of DG, basic scientific data reporting the chemical components are limited. In this study, 4-year-old curved ginseng (CG), one of the domestic DG products, was selected for further investigation. Eighty-six samples of 30 and 50 piece-grade CG, which are the most widely distributed in the market, were collected for 5 yr. Their major components, such as moisture, total sugar, acidic polysaccharides, total phenolic compounds, and saponins, were analyzed to figure out the standard quality characteristics. The moisture content of all CG samples was less than 15%. The total water-soluble sugar contents were 22.9% to 47.8% and 23.2% to 49.5% in the 30 and 50 piece-grade CG, respectively. The acidic polysaccharide contents were 3.6% to 6.7% and 2.9% to 6.9% in the 30 and 50 piece-grade CG, respectively. The total phenolic compound content was 0.4% to 0.5% in CG, regardless of the piece-grade. The crude saponin content, which represents the active component of ginseng, was over 2% in all samples. In 30 piece-grade CG samples, the contents of major ginsenosides, Rb1, Rf, and Rg1, were 2.2 to 4.7 mg/g, 0.4 to 1.3 mg/g, and 1.6 to 4.0 mg/g, respectively. The ginsenoside contents in 50 piece-grade CG samples were 2.1 to 3.9 mg/g (Rb1), 0.5 to 1.2 mg/g (Rf), and 1.3 to 3.4 mg/g (Rg1). Overall, since there were relatively high standard deviation and coefficient of variation in all the chemical component contents that were assessed, we found some difficulties in showing the CG standard chemical component characteristics by average, standard deviation, and other statistical analysis factors.

Anti-Fatigue Effects of Fermented Rhodiola rosea Extract in Mice

Rhodiola rosea is a perennial plant which grows in the alpine regions of Europe and Asia. Although the protective effects of R. rosea extract from fatigue due to exercise stress have been reported, studies on fermented R. rosea extract remain insufficient to date. Therefore, this study was conducted to examine the protective effects of fermented R. rosea extract against fatigue and exercise stress. As a result, fermented R. rosea extract was found to significantly increase swimming time, hepatic superoxide dismutase content, and serum lactate dehydrogenase in mice, while decreasing serum blood urea nitrogen content compared to R. rosea extract. Given the above results, it is considered that fermented R. rosea extract effectively protects against fatigue caused by strenuous exercise.

Inhibitory effects of ginseng seed on melanin biosynthesis

Background: Ginseng root has been traditionally used for the treatment of many diseases in Korea. However, so far ginseng seed has been mostly unused and discarded. As part of our ongoing research on the ginseng seeds, the inhibitory effect of ginseng seeds on melanin production was verified to assess their potential as a skin depigmenting substance. Materials and Methods: The present study measured the inhibitory effect of ginseng seeds on melanin production through the tyrosinase inhibitory effect and analyzed their effects on melanin production in melan-a-cells. Results: Ethanol extract of ginseng seed was applied to melan-a-cells at a concentration of 100 ppm and melanin production was reduced by 35.1% without cytotoxicity. In addition, the ethanol extract of ginseng seed was shown to reduce tyrosinase activity. Conclusion: Because the results showed excellent melanin inhibitory activity compared with that obtained by arbutin, ethanol extracts of ginseng leaf and ginseng root at the same concentration, it can be concluded that ginseng seeds show great potential as a skin depigmenting substance.