• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.397-404
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• 2009

For standardization of LMK02 quality, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelica gigas Nakai in the constituents of LMK02 were estimated as indicative components. From LMK02 water extract, has been used in vitro test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease (AD). $A{\beta}$ oligomer derived from proteolytic processing of the ${\beta}$-amyloid precursor protein (APP), including the amyloid-${\beta}$ peptide ($A{\beta}$), play a critical role in the pathogenesis of Alzheimer's dementia. We determined that oligomer amyloid-${\beta}$ ($A{\beta}$) have a profound attenuation in the increase in rat hippocampus H19-7 cells from. Experimental evidence indicates that LMK02 protects against neuronal damage from cells, but its cellular and molecular mechanisms remain unknown. Using a hippocampus cell line on $A{\beta}$ oligomer-induced neuronal cytotoxicity, we demonstrated that LMK02 inhibits formation of $A{\beta}$ oligomer, which are the behavior, and possibly causative, feature of AD. In the Red Ginseng, the average amounts of Ginsenoside Rg3 were $47.04{\mu}g/g$ and $42.3{\mu}g/g$, 90 % of its weight were set as a standard value. And, in the Angelica gigas Nakai, the average amounts of Decursin were 2.71 mg/g and 2.44mg/g, 90 % of its weight were also set as a standard value. The attenuated $A{\beta}$ oligomer in the presence of LMK02 was observed in the conditioned medium of this $A{\beta}$ oligomer-induced cells under in vitro. In the cells, LMK02 significantly activated antiapoptosis and decreased the production of ROS. These results suggest that neuronal damage in AD might be due to two factors: a direct $A{\beta}$ oligomer toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of $A{\beta}$ oligomer, underlie the neuroprotective effects of LMK02 treatment.

• Korean Journal of Soil Science and Fertilizer
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• v.19 no.1
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• pp.56-62
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• 1986

Fertilization response on production and quality of flue-cured tobacco as to different level of nitrogen, phosphorus, and potassium were studied in a field experiment. The results were summarized as follows: 1. Growth and yield of flue-cured tobacco were significantly better in higher nitrogen fertilization levels, regardless of soil fertility, but the negative correlation was recognized between the quality of leaves and the amounts of nitrogen application. While, both fertilizers of phosphorous and potassium did not have should little effect on the tobacco yield and quality. 2. The optimum ratio of N, P, and K fertilizer applications were decided by the appearance of the proper yield and the best quality of tobacco leaves. The proportion of N:P:K was 2:1:4. 3. The single effect (Complete plot minus Non-fertilized plot) of N, P, and K on yield and quality of cured leaf was greatly affected by nitrogen, but the combined effect (Nutrient deficiency plot minus Non-fertilzier plot) of that were only slightly affected by P and K.

• 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.40 no.4
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• pp.351-358
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• 2016

Background: This study was designed to investigate whether ginsenoside Rb1 (Rb1) and compound K (CK) ameliorated insulin resistance by suppressing endoplasmic reticulum (ER) stress-induced inflammation in adipose tissue. Methods: To induce ER stress, epididymal adipose tissue from mice or differentiated 3T3 adipocytes were exposed to high glucose. The effects of Rb1 and CK on reactive oxygen species production, ER stress, TXNIP/NLRP3 inflammasome activation, inflammation, insulin signaling activation, and glucose uptake were detected by western blot, emzyme-linked immunosorbent assay, or fluorometry. Results: Rb1 and CK suppressed ER stress by dephosphorylation of $IRE1{\alpha}$ and PERK, thereby reducing TXNIP-associated NLRP3 inflammasome activation in adipose tissue. As a result, Rb1 and CK inhibited IL-$1{\beta}$ maturation and downstream inflammatory factor IL-6 secretion. Inflammatory molecules induced insulin resistance by upregulating phosphorylation of insulin receptor substrate-1 at serine residues and impairing insulin PI3K/Akt signaling, leading to decreased glucose uptake by adipocytes. Rb1 and CK reversed these changes by inhibiting ER stress-induced inflammation and ameliorating insulin resistance, thereby improving the insulin IRS-1/PI3K/Akt-signaling pathway in adipose tissue. Conclusion: Rb1 and CK inhibited inflammation and improved insulin signaling in adipose tissue by suppressing ER stress-associated NLRP3 inflammation activation. These findings offered novel insight into the mechanism by which Rb1 and CK ameliorate insulin resistance in adipose tissue.

• Korean Journal of Food Science and Technology
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• v.33 no.1
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• pp.135-141
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• 2001

Of hot-water extracts prepared from 10 herbal components of Sip-Jeon-Dae-Bo-Tang, Atractylodes lancea DC. (ALR) and Panax ginseng C.A. Meyer (PG) showed the most potent bone marrow cell proliferation activity through intestinal immune system whereas other extracts did not have the activity except for Astragalus membranacues Bunge (ASR) and Angelica acutiloba Kitagawa (AR) having low activity. Especially, ALR had the potent activity irrespective of classes of ALR, a place of production and the condition of breeding. In addition, we found that hot-water extract from Atractylodes lancea DC rhizomes (ALR-0) contributed mainly to Peyer's patch cells mediated-hematopoietic response of Sip-Jeon-Dae-Bo-Tang. ALR-0 was further fractionated into MeOH-soluble fraction (ALR-1), MeOH-insoluble and EtOH-soluble fraction (ALR-2), and the crude polysaccharide fraction (ALR-3). Among these fractions, only ALR-3 showed potent stimulating activity for proliferation of bone marrow cells mediated by Peyer's patch cells, dose-dependently. In treatments of ALR-3 with $NaIO_4,\;NaClO_2$ and pronase, all significantly reduced the intestinal immune system modulating activity of ALR-3, and the activity of ALR-3 was much affected by $NaIO_4$ oxidation particularly. These results reveal that macromolecules, such as polysaccharide, rather than low-molecular-weight substances, are the potent intestinal immune system modulating compound of ALR.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.258-266
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• 2020

Background: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study. Methods: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein. Results: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (-6.426 kcal/mol), and the binding was stable. GRb1 significantl reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity in vitro, with a half-maximal effective concentration of ≈2.317 μM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells. Conclusion: GRb1 is a potential natural GR agonist that protects against oxidative stress-induced apoptosis of H9C2 cells.

• Korean Journal of Poultry Science
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• v.46 no.2
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• pp.95-103
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• 2019

This study investigated the effect of traditional medicinal plants on the quality characteristics of Samgyetang breast meat and broth. The traditional medicinal plants used in this study were roots of Panax ginseng, Codonopsis lanceolata, Platycodon grandiflorum, Salvia miltiorrhiza, Adenophora triphylla, and Allium hookeri. There was no significant difference (P>0.05) in the moisture, protein, ash content, water holding capacity, and cooking loss of Samgyetang meat with the addition of traditional medicinal plants. The color values (lightness, redness, and yellowness) of Samgyetang meat and broth were significantly different (P<0.05); the 2-thiobarbituric acid reactive substances and shear force of Samgyetang meat were significantly different (P<0.05); and the pH, turbidity, and viscosity of Samgyetang broth were also significantly different (P<0.05) with the addition of traditional medicinal plants. In the overall acceptability of Samgyetang meat, the addition of S. miltiorrhiza showed the highest score compared to that of other treatments (P<0.05). Thus, the addition of traditional medicinal plants in the production of Samgyetang were found to affect the lipid rancidity beneficially with plant species when compared to Samgyetang with Panax ginseng. In conclusion, with the development of Samgyetang using S. miltiorrhiza, it will be possible to develop products with superior quality characteristics in antioxidant, shear force, and overall acceptability.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.305-315
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• 2021

Background: Panax stipuleanatus represents a folk medicine for treatment of inflammation. However, lack of experimental data does not confirm its function. This article aims to investigate the analgesic and anti-inflammatory activities of triterpenoid saponins isolated from P. stipuleanatus. Methods: The chemical characterization of P. stipuleanatus allowed the identification and quantitation of two major compounds. Analgesic effects of triterpenoid saponins were evaluated in two models of thermal- and chemical-stimulated acute pain. Anti-inflammatory effects of triterpenoid saponins were also evaluated using four models of acetic acid-induced vascular permeability, xylene-induced ear edema, carrageenan-induced paw edema, and cotton pellet-induced granuloma in mice. Results: Two triterpenoid saponins of stipuleanosides R₁ (SP-R₁) and R₂ (SP-R₂) were isolated and identified from P. stipuleanatus. The results showed that SP-R₁ and SP-R₂ significantly increased the latency time to thermal pain in the hot plate test and reduced the writhing response in the acetic acid-induced writhing test. SP-R₁ and SP-R₂ caused a significant decrease in vascular permeability, ear edema, paw edema, and granuloma formation in inflammatory models. Further studies showed that the levels of inflammatory mediators, nitric oxide, malondialdehyde, tumor necrosis factor-α, and interleukin 6 in paw tissues were downregulated by SP-R₁ and SP-R₂. In addition, the rational harvest of three- to five-year-old P. stipuleanatus was preferable to obtain a higher level of triterpenoid saponins. SP-R₂ showed the highest content in P. stipuleanatus, which had potential as a chemical marker for quality control of P. stipuleanatus. Conclusion: This study provides important basic information about utilization of P. stipuleanatus resources for production of active triterpenoid saponins.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.295-304
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• 2021

Background: Acute promyelocytic leukemia (APL) is a hematopoietic malignancy driven by promyelocytic leukemia-retinoic acid receptor A (PML-RARA) fusion gene. The therapeutic drugs currently used to treat APL have adverse effects. 20(S)-ginsenoside Rh2 (GRh2) is an anticancer medicine with high effectiveness and low toxicity. However, the underlying anticancer mechanisms of GRh2-induced PML-RARA degradation and apoptosis in human APL cell line (NB4 cells) remain unclear. Methods: Apoptosis-related indicators and PML-RARA expression were determined to investigate the effect of GRh2 on NB4 cells. Z-VAD-FMK, LY294002, and C 87, as inhibitors of caspase, and the phosphatidylinositol 3-kinase (PI3K) and tumor necrosis factor-α (TNF-α) pathways were used to clarify the relationship between GRh2-induced apoptosis and PML-RARA degradation. Results: GRh2 dose- and time-dependently decreased NB4 cell viability. GRh2-induced apoptosis, cell cycle arrest, and caspase3, caspase8, and caspase9 activation in NB4 cells after a 12-hour treatment. GRh2-induced apoptosis in NB4 cells was accompanied by massive production of reactive oxygen species, mitochondrial damage and upregulated Bax/Bcl-2 expression. GRh2 also induced PML/PML-RARA degradation, PML nuclear bodies formation, and activation of the downstream p53 pathway in NB4 cells. Z-VAD-FMK inhibited caspase activation and significantly reversed GRh2-induced apoptosis and PML-RARA degradation. GRh2 also upregulated TNF-α expression and inhibited Akt phosphorylation. LY294002, an inhibitor of the PI3K pathway, enhanced the antitumor effects of GRh2, and C 87, an inhibitor of the TNF-α pathway, reversed NB4 cell viability, and GRh2-mediated apoptosis in a caspase-8-dependent manner. Conclusion: GRh2 induced caspase-dependent PML-RARA degradation and apoptosis in NB4 cells via the Akt/Bax/caspase9 and TNF-α/caspase8 pathways.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.418-425
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• 2022

Background: Sorafenib is effective in treating hepatoma, but most patients develop resistance to it. STAT3 signaling has been implicated in sorafenib resistance. Artesunate (ART) and 20(R)-ginsenoside Rg3 (Rg3) have anti-hepatoma effects and can inhibit STAT3 signaling in cancer cells. This study aimed to evaluate the effects of Rg3 in combination with ART (Rg3-plus-ART) in overcoming sorafenib resistance, and to examine the involvement of STAT3 signaling in these effects. Methods: Sorafenib-resistant HepG2 cells (HepG2-SR) were used to evaluate the in vitro anti-hepatoma effects of Rg3-plus-ART. A HepG2-SR hepatoma-bearing BALB/c-nu/nu mouse model was used to assess the in vivo anti-hepatoma effects of Rg3-plus-ART. CCK-8 assays and Annexin V-FITC/PI double staining were used to examine cell proliferation and apoptosis, respectively. Immunoblotting was employed to examine protein levels. ROS generation was examined by measuring DCF-DA fluorescence. Results: Rg3-plus-ART synergistically reduced viability of, and evoked apoptosis in HepG2-SR cells, and suppressed HepG2-SR tumor growth in mice. Mechanistic studies revealed that Rg3-plus-ART inhibited activation/phosphorylation of Src and STAT3 in HepG2-SR cultures and tumors. The combination also decreased the STAT3 nuclear level and induced ROS production in HepG2-SR cultures. Furthermore, overactivation of STAT3 or removal of ROS diminished the anti-proliferative effects of Rg3-plus-ART, and removal of ROS diminished Rg3-plus-ART's inhibitory effects on STAT3 activation in HepG2-SR cells. Conclusions: Rg3-plus-ART overcomes sorafenib resistance in experimental models, and inhibition of Src/STAT3 signaling and modulation of ROS/STAT3 signaling contribute to the underlying mechanisms. This study provides a pharmacological basis for developing Rg3-plus-ART into a novel modality for treating sorafenib-resistant hepatoma.