• Journal of Ginseng Research
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• v.45 no.4
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• pp.465-472
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• 2021

Background: Ginseng can help regulate brain excitability, promote learning and memory, and resist cerebral ischemia in the central nervous system. Ginsenosides are the major effective compounds of Ginseng, but their protein targets in the brain have not been determined. Methods: We screened proteins that interact with the main components of ginseng (ginsenosides) by affinity chromatography and identified the 14-3-3 ζ protein as a potential target of ginsenosides in brain tissues. Results: Biolayer interferometry (BLI) analysis showed that 20(S)-protopanaxadiol (PPD), a ginseng saponin metabolite, exhibited the highest direct interaction to the 14-3-3 ζ protein. Subsequently, BLI kinetics analysis and isothermal titration calorimetry (ITC) assay showed that PPD specifically bound to the 14-3-3 ζ protein. The cocrystal structure of the 14-3-3 ζ protein-PPD complex showed that the main interactions occurred between the residues R56, R127, and Y128 of the 14-3-3 ζ protein and a portion of PPD. Moreover, mutating any of the above residues resulted in a significant decrease of affinity between PPD and the 14-3-3 ζ protein. Conclusion: Our results indicate the 14-3-3 ζ protein is the target of PPD, a ginsenoside metabolite. Crystallographic and mutagenesis studies suggest a direct interaction between PPD and the 14-3-3 ζ protein. This finding can help in the development of small-molecular compounds that bind to the 14-3-3 ζ protein on the basis of the structure of dammarane-type triterpenoid.

• The Korea Journal of Herbology
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• v.25 no.3
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• pp.123-130
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• 2010

Objectives & Method：We investigated adverse symptoms, toxicity, treatment and prevention against adverse effects of restoratives for invigorating qi(補氣藥) in order to use herbal medicines accurately. Result：Ginseng Radix(人參), Codonopsis Pilosulae Radix(黨參), Panacis Quinquefolii Radix(西洋參), Astragali Radix(黃芪), Atractylodis Rhizoma Alba(白朮), Dioscoreae Rhizoma(山藥), Dolichoris Semen(白扁豆), Glycyrrhizae Radix(甘草), Jujubae Fructus(大棗) and Mel(蜂蜜) may give rise to some side effects, allergic reaction or toxic symptoms in restoratives for invigorating qi(補氣藥). The representative methods of poisoning treatment in western medicines are stopping medication, washing out the stomach, promotion of vomiting, causing diarrhea, supplies of grape sugar and symptomatic treatment, etc. The representative methods of poisoning treatment in oriental medicine take advantage of various herbs. And Oriental medical doctor should meet symptoms as patients call for attention. In order to prevent against poisoning of restoratives for invigorating qi(補氣藥), the patients should keep usage, dosage and notes. Conclusion：We should pay attention to clinical using of Ginseng Radix(人參), Codonopsis Pilosulae Radix(黨參), Panacis Quinquefolii Radix(西洋參), Astragali Radix(黃芪), Atractylodis Rhizoma Alba(白朮), Dioscoreae Rhizoma (山藥), Dolichoris Semen(白扁豆), Glycyrrhizae Radix(甘草), Jujubae Fructus(大棗) and Mel(蜂蜜) in restoratives for invigorating qi(補氣藥).

• Journal of Ginseng Research
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• v.47 no.4
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• pp.572-582
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• 2023

Background: Free fatty acid-induced lipotoxicity is considered to play an important role in pancreatic β-cell dysfunction. The effect of ginsenosides on palmitic acid-induced pancreatic beta-cells cell death and failure of glucose-stimulated secretion of insulin (GSIS) was evaluated in this study. Methods: Enzyme-linked immunosorbent assay kit for a rat insulin was used to quantify glucose-stimulated insulin secretion. Protein expression was examined by western blotting analysis. Nuclear condensation was measured by staining with Hoechst 33342 stain. Apoptotic cell death was assessed by staining with Annexin V. Oil Red O staining was used to measure lipid accumulation. Results: We screened ginsenosides to prevent palmitic acid-induced cell death and impairment of GSIS in INS-1 pancreatic β-cells and identified protopanaxadiol (PPD) as a potential therapeutic agent. The protection effect of PPD was likely due to a reduction in apoptosis and lipid accumulation. PPD attenuated the palmitic acid-induced increase in the levels of B-cell lymphoma-2-associated X/B-cell lymphoma 2, poly (ADP-ribose) polymerase and cleaved caspase-3. Moreover, PPD prevented palmitic acid-induced impairment of insulin secretion, which was accompanied by an increase in the activation of phosphatidylinositol 3-kinase, peroxisome proliferator-activated receptor γ, insulin receptor substrate-2, serine-threonine kinase, and pancreatic and duodenal homeobox-1. Conclusion: Our results suggest that the protective effect of PPD on lipotoxicity and lipid accumulation induced by palmitic acid in pancreatic β-cells.

• Journal of Ginseng Research
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• v.44 no.3
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• pp.475-482
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• 2020

Background: Active natural ingredients, especially small molecules, have recently received wide attention as modifiers used to treat neurodegenerative disease by promoting neurogenic regeneration of neural stem cell (NSC) in situ. 20(S)-protopanaxadiol (PPD), one of the bioactive ingredients in ginseng, possesses neuroprotective properties. However, the effect of PPD on NSC proliferation and differentiation and its mechanism of action are incompletely understood. Methods: In this study, we investigated the impact of PPD on NSC proliferation and neuronal lineage differentiation through activation of the Wnt/glycogen synthase kinase (GSK)-3β/β-catenin pathway. NSC migration and proliferation were investigated by neurosphere assay, Cell Counting Kit-8 assay, and EdU assay. NSC differentiation was analyzed by Western blot and immunofluorescence staining. Involvement of the Wnt/GSK3β/β-catenin pathway was examined by molecular simulation and Western blot and verified using gene transfection. Results: PPD significantly promoted neural migration and induced a significant increase in NSC proliferation in a time- and dose-dependent manner. Furthermore, a remarkable increase in anti-microtubule-associated protein 2 expression and decrease in nestin protein expression were induced by PPD. During the differentiation process, PPD targeted and stimulated the phosphorylation of GSK-3β at Ser9 and the active forms of β-catenin, resulting in activation of the Wnt/GSK-3β/β-catenin pathway. Transfection of NSCs with a constitutively active GSK-3β mutant at S9A significantly hampered the proliferation and neural differentiation mediated by PPD. Conclusion: PPD promotes NSC proliferation and neural differentiation in vitro via activation of the Wnt/GSK-3β/β-catenin pathway by targeting GSK-3β, potentially having great significance for the treatment of neurodegenerative diseases.

• Nutrition Research and Practice
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• v.11 no.5
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• pp.365-372
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• 2017

BACKGROUND/OBJECTIVES: Owing to health concerns related to the consumption of traditional snacks high in sugars and fats, much effort has been made to develop functional snacks with low calorie content. In this study, a new recipe for Korean rice cookie, dasik, was developed and its antioxidative, lipid-lowering, and anti-inflammatory effects and related mechanisms were elucidated. The effects were compared with those of traditional rice cake dasik (RCD), the lipid-lowering effect of which is greater than that of traditional western-style cookies. MATERIALS/METHODS: Ginseng-added brown rice dasik (GBRD) was prepared with brown rice flour, fructooligosaccharide, red ginseng extract, and propolis. Mice were grouped (n = 7 per group) into those fed a normal AIN-76 diet, a high-fat diet (HFD), and HFD supplemented with RCD or GBRD. Dasik in the HFD accounted for 7% of the total calories. The lipid, reactive oxygen species, and peroxynitrite levels, and degree of lipid peroxidation in the plasma or liver were determined. The expression levels of proteins involved in lipid metabolism and inflammation, and those of antioxidant enzymes were determined by western blot analysis. RESULTS: The plasma and hepatic total cholesterol concentrations in the GBRD group were significantly decreased via downregulation of sterol regulatory element-binding protein-2 and 3-hydroxy-3-methylglutaryl-CoA reductase (P < 0.05). The hepatic peroxynitrite level was significantly lower, whereas glutathione was higher, in the GBRD group than in the RCD group. Among the antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx) were significantly upregulated in the GBRD group (P < 0.05). In addition, nuclear factor-kappaB (NF-${\kappa}B$) expression in the GBRD group was significantly lower than that in the RCD group. CONCLUSIONS: GBRD decreases the plasma and hepatic cholesterol levels by downregulating cholesterol synthesis. This new dasik recipe also improves the antioxidative and anti-inflammatory status in HFD-fed mice via CAT and GPx upregulation and NF-${\kappa}B$ downregulation. These effects were significantly higher than those of RCD.

• Journal of Ginseng Research
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• v.42 no.1
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• pp.50-56
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• 2018

Background: Saponins from Panax japonicus (SPJ) are the most abundant and main active components of P. japonicus, which replaces ginseng roots in treatment for many kinds of diseases in the minority ethnic group in China. Our previous studies have demonstrated that SPJ has the effects of anti-inflammation through the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-${\kappa}B$) signaling pathways. The present study was designed to investigate whether SPJ can modulate intestinal tight junction barrier in aging rats and further to explore the potential mechanism. Methods: Aging rats had been treated with different doses (10 mg/kg, 30 mg/kg, and 60 mg/kg) of SPJ for 6 mo since they were 18 mo old. After the rats were euthanized, the colonic samples were harvested. Levels of tight junctions (claudin-1 and occludin) were determined by immunohistochemical staining. Levels of proinflammatory cytokines (interleukin-$1{\beta}$ and tumor necrosis factor-${\alpha}$) were examined by Western blot. NF-${\kappa}B$ and phosphorylation of MAPK signaling pathways were also determined by Western blot. Results: We found that SPJ increased the expression of the tight junction proteins claudin-1 and occludin in the colon of aging rats. Treatment with SPJ decreased the levels of interleukin-$1{\beta}$ and tumor necrosis factor-${\alpha}$, reduced the phosphorylation of three MAPK isoforms, and inhibited the expression of NF-${\kappa}B$ in the colon of aging rats. Conclusion: The studies demonstrated that SPJ modulates the damage of intestinal epithelial tight junction in aging rats, inhibits inflammation, and downregulates the phosphorylation of the MAPK and $NF-{\kappa}B$ signaling pathways.

• Journal of Ginseng Research
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• v.48 no.4
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• pp.395-404
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• 2024

Background: Ginsenoside Rg₁ (Rg₁) is one of the main active components in Chinese medicines, Panax ginseng and Panax notoginseng. Research has shown that Rg₁ has a protective effect on the cardiovascular system, including anti-myocardial ischemia-reperfusion injury, anti-apoptosis, and promotion of myocardial angiogenesis, suggesting it a potential cardiovascular agent. However, the protective mechanism involved is still not fully understood. Methods: Based on network pharmacology, ligand-based protein docking, proteomics, Western blot, protein recombination and spectroscopic analysis (UV-Vis and fluorescence spectra) techniques, potential targets and pathways for Rg₁ against myocardial ischemia (MI) were screened and explored. Results: An important target set containing 19 proteins was constructed. Two target proteins with more favorable binding activity for Rg₁ against MI were further identified by molecular docking, including mitogen-activated protein kinase 1 (MAPK1) and adenosine kinase (ADK). Meanwhile, Rg₁ intervention on H9c2 cells injured by H₂O₂ showed an inhibitory oxidative phosphorylation (OXPHOS) pathway. The inhibition of Rg₁ on MAPK1 and OXPHOS pathway was confirmed by Western blot assay. By protein recombination and spectroscopic analysis, the binding reaction between ADK and Rg₁ was also evaluated. Conclusion: Rg₁ can effectively alleviate cardiomyocytes oxidative stress injury via targeting MAPK1 and ADK, and inhibiting oxidative phosphorylation (OXPHOS) pathway. The present study provides scientific basis for the clinical application of the natural active ingredient, Rg₁, and also gives rise to a methodological reference to the searching of action targets and pathways of other natural active ingredients.

• The Korea Journal of Herbology
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• v.30 no.5
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• pp.59-65
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• 2015

Objectives : Fermentation of herbs has been known to be helpful in improving the immune systems and protecting body against disease. The present study was conducted to evaluate anti-inflammatory effects of the fermentation extracts (FE) consisting of soybean, red ginseng andCitrus UnshiuPeel in lipopolysaccharide (LPS)-activated Raw264.7 cells.Methods : FE were prepared by the fermentation withBacillus Subtilisand then by extraction with ethanol (95%; prepared by the fermentation process). Cell viability was measured by MTT assay. Nitric oxide (NO) production was measured in culture media by Griess assay. The expression of nuclear factor (NF)-κB and inhibitory kappa B alpha (IκBα) was determined by Western blot.Results : LPS-induced production of NO and PGE₂was dose-dependently decreased by the treatment of FE in Raw264.7 cells. These suppressive effects of FE on NO and PGE₂production were related to the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. FE inhibited LPS-induced production of pro-inflammatory cytokines, TNF-α, IL-6, and IL-1βin a dose-dependent manner. Furthermore, FE inhibited the NF-κB signaling pathway through the prevention of LPS-induced degradation of IκBαin cytosol and the nuclear translocation of NF-κB.Conclusions : These findings suggest that FE could have anti-inflammatory effects on LPS-induced inflammatory responses in macrophages.

• The Journal of Korean Medical History
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• v.30 no.2
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• pp.63-71
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• 2017

Traditional Asian medicine has an extensive evidence base built upon thousands of years of experience within Asia, of curing various diseases. Only recently, within the past two centuries, have modern medical scientists developed interest in traditional Asian medicine. Asian Medicine seems to be regarded only as an adjunctive medicine and viewed as alargely un-proven alternative medicine to complement western medicine, used in some cases to establish a new paradigm of "integrative medicine". This article reviews how Korean herbal cosmetics emerged by applying traditional Asian medicine to the science of cosmetics. The characteristics of Korean herbal cosmetics are examined through examples of history, concepts and traditions. With the advancements in biotechnology, studies are now being conducted on the dermatological effects and processing methods of herbal ingredients, including ginseng. The authors explain the current research on the identification on the active ingredients of herbs, extraction methods, and bio-processing of ingredients to improve the biological efficacies of herbs on the skin. A summary of studies focused on modern reinterpretations of ageing theories, such as 'Seven year aging cycle', are provided. In conclusion, the development of Korean cosmetics products are based on the accumulated knowledge of thousands of years of experience including; 1) practical heritage of traditional Asian medicines such as Donguibogam; 2) excellent medicinal plants, such as ginseng, which are native to Korea; and 3) innovative attempts to modernize materials, processes, and principles.

• Advances in Traditional Medicine
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• v.8 no.4
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• pp.440-447
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• 2008

This study investigated the role of Panax ginseng (PG) on the phorbol myristate acetate (PMA) + calcium ionophore A23187-induced hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) activation, phosphorylation of the extracellular signal-regulated kinase (ERK), and inflammatory cytokine production from the human mast cell line, HMC-1. HIF-$1{\alpha}$ and phosphorylation of ERK were observed by Western blotting. The inflammatory cytokine production was determined by enzyme-linked immunosorbent assay. PG inhibited the PMA+A23187-induced HIF-$1{\alpha}$ expression and the subsequent production of vascular endothelial growth factor. In addition, PG suppressed PMA + A23187-induced phosphorylation of ERK. We also show that the increased cytokines interleukin (IL)-$1{\beta}$, IL-6, and tumour necrosis factor-${\alpha}$ level was significantly inhibited by treatment of PG. In the present study, we report for the first time that PG is an inhibitor of HIF-$1{\alpha}$ and cytokines on the mast cell-mediated inflammatory responses.