• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.127-132
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• 2013

Ginsenosides, one of the active ingredients of Panax ginseng, show various pharmacological and physiological effects, and they are converted into compound K (CK) or protopanaxatriol (M4) by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. The ${\gamma}$-aminobutyric acid $receptor_C$ ($GABA_C$) is primarily expressed in retinal bipolar cells and several regions of the brain. However, little is known of the effects of ginsenoside metabolites on $GABA_C$ receptor channel activity. In the present study, we examined the effects of CK and M4 on the activity of human recombinant $GABA_C$ receptor (${\rho}$ 1) channels expressed in Xenopus oocytes by using a 2-electrode voltage clamp technique. In oocytes expressing $GABA_C$ receptor cRNA, we found that CK or M4 alone had no effect in oocytes. However, co-application of either CK or M4 with GABA inhibited the GABA-induced inward peak current ($I_{GABA}$). Interestingly, pre-application of M4 inhibited $I_{GABA}$ more potently than CK in a dose- dependent and reversible manner. The half-inhibitory concentration ($IC_{50}$) values of CK and M4 were $52.1{\pm}2.3$ and $45.7{\pm}3.9{\mu}M$, respectively. Inhibition of $I_{GABA}$ by CK and M4 was voltage-independent and non-competitive. This study implies that ginsenoside metabolites may regulate $GABA_C$ receptor channel activity in the brain, including in the eyes.

• Journal of Ginseng Research
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• v.42 no.2
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• pp.165-174
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• 2018

Background: Extended endoplasmic reticulum (ER) stress may initiate apoptotic pathways in cancer cells, and ER stress has been reported to possibly increase tumor death in cancer therapy. We previously reported that caspase-8 played an important role in compound K-induced apoptosis via activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation in HL-60 human leukemia cells. The mechanisms leading to apoptosis in A549 and SK-MES-1 human lung cancer cells and the role of ER stress have not yet been understood. Methods: The apoptotic effects of compound K were analyzed using flow cytometry, and the changes in protein levels were determined using Western blot analysis. The intracellular calcium levels were monitored by staining with Fura-2/AM and Fluo-3/AM. Results: Compound K-induced ER stress was confirmed through increased phosphorylation of $eIF2{\alpha}$ and protein levels of GRP78/BiP, XBP-1S, and $IRE1{\alpha}$ in human lung cancer cells. Moreover, compound-K led to the accumulation of intracellular calcium and an increase in m-calpain activities that were both significantly inhibited by pretreatment either with BAPTA-AM (an intracellular $Ca^{2+}$ chelator) or dantrolene (an RyR channel antagonist). These results were correlated with the outcome that compound K induced ER stress-related apoptosis through caspase-12, as z-ATAD-fmk (a specific inhibitor of caspase-12) partially ameliorated this effect. Interestingly, 4-PBA (ER stress inhibitor) dramatically improved the compound K-induced apoptosis. Conclusion: Cell survival and intracellular $Ca^{2+}$ homeostasis during ER stress in human lung cancer cells are important factors in the induction of the compound K-induced apoptotic pathway.

• Food Science and Preservation
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• v.18 no.2
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• pp.178-183
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• 2011

The consumer awareness concerning coffee beverages has increased in Korea. The objective of this study was to optimize the roasting conditions of coffee bean for consumer's attribute. The optimal roasting conditions for Colombian coffee beans were analyzed by using a central composite design with a quadratic polynomial model by response surface methodology (RSM). The experimental conditions for coffee bean roasting were $194.82^{\circ}C{\sim}250.00^{\circ}C$ and 7.93~22.07 minutes. The responses of sensory attributes. physicochemical and physical properties were analyzed with RSM. The width. length and height of green beans increased when the beans were roasted. The higher degree of roasting gave the higher pH and solid contents but the lower total acidity and total phenolic compounds. In sensory tests, the roasting temperature and time had a significant effect on the flavor score. The optimum roasting condition of Colombian coffee bean predicted for maximizing the length, width, solid contents, total phenolic compounds and flavor score were 20 minutes at $225^{\circ}C$ by RSM.

• Food Science and Preservation
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• v.16 no.2
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• pp.155-159
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• 2009

Physicochemical properties of sponge cakes prepared using various amounts of rosemary powder were evaluated. Rosemary powder was used at 0, 0.1, 0.3, 0.5, and 0.7%(w/w). The second-stage specific densities of batter increased from 0.49 to 0.54 as the amount of rosemary powder rose from 0% to 0.7%(w/w). All specific densities were within the normal range. The pH of sponge cake batters increased as rosemary powder proportion rose, with statistical significance(p<0.05). The moisture contents of cake showed no difference on the first day but significantly decreased to 38.5-39.7% after 3 days. The acid values and peroxide values fell as the proportion of rosemary powder increased. With rising rosemary powder level, antioxidative capacity increased but physiological properties were not affected in the range of rosemary powder concentrations used in this study.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.315-324
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• 2016

Background: Biocontrol agents are regarded as promising and environmental friendly approaches as agrochemicals for phytodiseases that cause serious environmental and health problems. Trichoderma species have been widely used in suppression of soil-borne pathogens. In this study, an endophytic fungus, Trichoderma gamsii YIM PH30019, from healthy Panax notoginseng root was investigated for its biocontrol potential. Methods: In vitro detached healthy roots, and pot and field experiments were used to investigate the pathogenicity and biocontrol efficacy of T. gamsii YIM PH30019 to the host plant. The antagonistic mechanisms against test phytopathogens were analyzed using dual culture, scanning electron microscopy, and volatile organic compounds (VOCs). Tolerance to chemical fertilizers was also tested in a series of concentrations. Results: The results indicated that T. gamsii YIM PH30019 was nonpathogenic to the host, presented appreciable biocontrol efficacy, and could tolerate chemical fertilizer concentrations of up to 20%. T. gamsii YIM PH30019 displayed antagonistic activities against the pathogenic fungi of P. notoginseng via production of VOCs. On the basis of gas chromatography-mass spectrometry, VOCs were identified as dimethyl disulfide, dibenzofuran, methanethiol, ketones, etc., which are effective ingredients for antagonistic activity. T. gamsii YIM PH30019 was able to improve the seedlings' emergence and protect P. notoginseng plants from soil-borne disease in the continuous cropping field tests. Conclusion: The results suggest that the endophytic fungus T. gamsii YIM PH30019 may have a good potential as a biological control agent against notoginseng phytodiseases and can provide a clue to further illuminate the interactions between Trichoderma and phytopathogens.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.247-257
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• 2020

Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.126-133
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• 2021

Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the aglycone derivatives of major ginsenosides, has been shown to have an anticancer activity toward a variety of cancers. This study was initiated with an attempt to evaluate its anti-cancer activity toward human endometrial cancer by cell and xenograft mouse models. Methods: Human endometrial cancer (HEC)-1A cells were incubated with different 20(S)-PPD concentrations. 20(S)-PPD cytotoxicity was evaluated using MTT assay. Apoptosis was detected using the annexin V binding assay and cell cycle analysis. Cleaved poly (ADP-ribose) polymerase (PARP) and activated caspase-9 were assessed using western blotting. HEC-1A cell tumor xenografts in athymic mice were generated by inoculating HEC-1A cells into the flank of BALB/c female mice and explored to validate 20(S)-PPD anti-endometrial cancer toxicity. Results: 20(S)-PPD inhibited HEC-1A cell proliferation in a dose-dependent manner with an IC50 value of 3.5 μM at 24 h. HEC-1A cells morphologically changed after 20(S)-PPD treatment, bearing resemblance to Taxol-treated cells. Annexin V-positive cell percentages were 0%, 10.8%, and 58.1% in HEC-1A cells when treated with 0, 2.5, and 5 μM of 20(S)-PPD, respectively, for 24 h. 20(S)-PPD subcutaneously injected into the HEC-1A cell xenograft-bearing mice three times a week for 17 days manifested tumor growth inhibition by as much as 18% at a dose of 80 mg/kg, which sharply contrasted to controls that showed an approximately 2.4-fold tumor volume increase. These events paralleled caspase-9 activation and PARP cleavage. Conclusion: 20(S)-PPD inhibits endometrial cancer cell proliferation by inducing cell death via a caspase-mediated apoptosis pathway. Therefore, the 20(S)-PPD-like ginsenosides are endowed with ample structural information that could be utilized to develop other ginsenoside-based anticancer agents.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.376-384
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• 2023

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

• Journal of Ginseng Research
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• v.30 no.3
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• pp.137-152
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• 2006

This study is for chemical relationships between ginsengs(2, 3 and 4 yr) and soils from three representative soil types of Keumsan, shale(SL), phyllite(PH) and granite(GR). In the weathered soils, the GR is mainly high. Positive relationships are dominant, and negative correlations are shown in the Y-Nb and Nb-Ta pairs. In the field soils, the GR is high while the SL is low. Regardless of the localities, available correlation relationships are dominant in the GR, and dominant in the 3 year area. In the host rocks, high element contents are shown in the GR. Positive relationships, regardless of the localities, are shown in the Zr-Hf, Ta, Nb-Ta and Hf-Ta pairs. In the ginsengs, chemical contents are distinctive with the different ages. Positive relationships are shown in the Y-Nb pair of the SL, Rb-Y pair of the PH, and Rb-Sr pair of the GR. Relative ratios(GR/SL and GR/PH) of the ginsengs suggest that ginsengs from the GR are higher than those of SL and PH while in the comparisons between PH and SL, 2 year ginsengs are high in the SL and 4 year ginsengs are high in the PH. Relative ratios between weathered and field soils (weathered/field) suggest high element contents in the weathered soils from the SL and PH and in the relative ratios(weathered soil/host rock), high element contents in weathered soils. Relative ratios between field soils and ginsengs(field soil/ginseng), regardless of the ages, show several ten and hundred times, suggestive of high contents in the soils. Comparisons with the overall average contents of each area show differences of several ten to hundred times in the SL and PH, and of several to ten times in the GR. These relationships suggest that contents of the ginsengs from the GR are more similar to the soils relative to those of SL and PH.

• The Korean Journal of Mycology
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• v.24 no.1 s.76
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• pp.38-48
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• 1996

The survival or colonization of beneficial organsisms and suppression of root rot of ginseng (Panax ginseng) by two distinct bacteria, Pseudomonas cepacia, Bacillus cereus and three mycorrhiza in pot soil were investigated and compared with uninoculated root. In separate inoculation, colonization of roots by P. cepacia was maintained at 6.25 (log cfu/g root) during growth for 10 days under pot culture conditions comparing to $5.62{\sim}6.19$ by mixed treatment with other organisms. Colonizations of P. cepacia were gradually decreased from 6.25 (log cfu/g root) in 10 days growth to 3.01 (log cfu/g root) in 270 days incubation period. This reduction was also investgated in combination treatments by B. cereus or F. solani. The numbers of Fusarium spp. were colonized high number in rhizosphere soil from 3.33 to 3.67 (log cfu/g root) in control within $10{\sim}60$days after treatment of pathogen F. solani, but it's numbers were markedly decreased in 270 days cultivation of plant from 3.33 to 1.02 (log cfu/g root) after treatment. In treatment of beneficial strains of P. cepacia and B. cereus, P. cepacia significantly suppressed the development of root rot from 4.3 in control to 1.2 in treatment, whereas B. cereus alone had no effect on the rate of disease suppression. The disease index $(1.8{\sim}2.3)$ in combination of two bacteria was reduced in plants inoculated with both P. cepacia and B. cereus comparing to the index (4.3) of control. As an effect of inoculation with mycorrhiza on disease suppression, suppression of root rot by F. solani was reduced to $1.2{\sim}1.6$ in disease index in treatment of Glomus albidum and Acaulospora longular comparing to 4.3 of control. In the treatment of bacterial strain P. cepacia and mycorrhizal fungus Glomus albidum, the disease suppression was apparent to 1.2 and 1.2 comparing to 4.3 of control in disease index respectively.