• 생명과학회지
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• 제25권3호
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• pp.317-322
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• 2015

알코올에 의한 지방간(지방변성증)은 에탄올 대사에 의해 감소되는 당량의 과도한 발생에 의해 유발된다. 일반적으로 만성적인 에탄올 투여는 간 지질의 합성을 증가시키는 sterol regulatory element-binding protein 1c (SREBP-1c)를 조절함으로써 지방변성증을 유발시킨다. SPEBP-1c에서 에탄올의 영향은 간에서의 지방대사를 조절하는 NAD⁺ 의존적 단백질 탈아세틸화효소인 mammalian sirtuin-1 (SIRT-1)에 의해 조정된다. 홍삼은 항당뇨와 항비만 효과를 위해 아시아에서 광범위하게 사용되는 한약재이다. 홍삼의 약리학적 치료학적인 효과는 진세노사이드와 같은 생물활성 성분에 의해 주로 일어난다. 따라서 우리는 마우스 간세포주인 AML-12 세포에서 SREBP-1과 SIRT-1에대한 한국홍삼 추출물의 조절효과를 평가하였다. 알코올과 홍삼추출물(0-1,000 μg/ml)을 AML-12 세포주에 처리하고, 지방소립을 Oil red O 염색법으로 확인하고, western blots을 사용해 SIRT-1과 SREBP-1의 발현을 확인하였다. 에탄올을 처리한 세포에서 홍삼추출물은 SIRT-1과 SREBP-1c의 발현을 회복시켰다. 또한 에탄올이 처리된 세포에서 홍삼추출물과 진세노사이드 Rb₂와 Rd가 SREBP-1을 유의적으로 감소시키는 것으로 확인 되었다. 결과적으로 홍삼과 활성 진세노사이드 성분인 Rb₂와 Rd가 SIRT-1과 간 지질대사를 변화시키는 SREBP-1c의 아세틸화의 조절을 통해 알코올에 의한 간지방변성을 억제하는 것을 확인하였다.

• Journal of Ginseng Research
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• 제45권5호
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• pp.583-590
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• 2021

Background: Gintonin, isolated from ginseng, acts as a ginseng-derived lysophosphatidic acid (LPA) receptor ligand and elicits the [Ca²⁺]_i transient through six LPA receptor subtypes (LPARSs). However, the long-term effects of gintonin-enriched fraction (GEF) on the gene expression of six LPARSs remain unknown. We examined changes in the gene expression of six LPA receptors in the mouse whole brain, heart, lungs, liver, kidneys, spleen, small intestine, colon, and testis after long-term oral GEF administration. Methods: C57BL/6 mice were divided into two groups: control vehicle and GEF (100 mg/kg, p.o.). After 21-day saline or GEF treatment, total RNA was extracted from nine mouse organs. Quantitative-real-time PCR (qRT-PCR) and western blot were performed to quantify changes in the gene and protein expression of the six LPARSs, respectively. Results: qRT-PCR analysis before GEF treatment revealed that the LPA6 RS was predominant in all organs except the small intestine. The LPA2 RS was most abundant in the small intestine. Long-term GEF administration differentially regulated the six LPARSs. Upon GEF treatment, the LPA6 RS significantly increased in the liver, small intestine, colon, and testis but decreased in the whole brain, heart, lungs, and kidneys. Western blot analysis of the LPA6 RS confirmed the differential effects of GEF on LPA6 receptor protein levels in the whole brain, liver, small intestine, and testis. Conclusion: The LPA6 receptor was predominantly expressed in all nine organs examined; long-term oral GEF administration differentially regulated LPA3, LPA4, and LPA6 receptors in the whole brain, heart, lungs, liver, kidneys, small intestine, and testis.

• 동의생리병리학회지
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• 제25권3호
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• pp.521-527
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• 2011

Recently, Korean ginseng, as immuno-activator, was actively investigated on its effect and mechanism. But purified fermented red ginseng (PFRG) has not been researched enough compared to red ginseng (RG, steamed and dried root of Panax ginseng C. A. Meyer, family Araliaceae) and fermented red ginseng (FRG, fermented red ginseng by Lactobacillus brevis 13094). In this study, we examined RG, FRG and PFRG to compare their anti-inflammatory effect by LPS. According to the result, RAW 264.7 cells survival rates did not largely change by RG and FRG. Only PFRG expressed weak toxicity at 10 ug/ml. The expression of iNOS and production of Nitric Oxide (NO) decreased depending on the concentration of RG, FRG and PFRG. And the expression of COX-2 also decreased. We tried western blotting for detecting that the expression of iNOS, COX-2 was caused by NF-${\kappa}B$. The result supported that the inhibition of NF-${\kappa}B$ by RG, FRG and PFRG suppressed the expression of iNOS, COX-2 and affected the production of TNF-${\alpha}$. While the anti-inflammatory effect was confirmed from all three types of red ginseng (RG, FRG, PFRG), the effect of PFRG was superior to others. Further research is required on other effects of PFRG.

• Journal of Acupuncture Research
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• 제21권6호
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• pp.1-17
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• 2004

Objective : To compare and examine how adjustment of pH and electrolyte can affect the efficacy of cultivated wild ginseng distilled herbal acupuncture, we've administered pure cultivated wild ginseng distilled herbal acupuncture and pH and electrolyte adjusted cultivated wild ginseng distilled herbal acupuncture on A549 human lung cancer lines. Then mRNA and proteins which take parts in apoptosis were examined. Methods : Pure cultivated wild ginseng distilled herbal acupuncture treated group was set as the control group and pH and electrolyte adjusted cultivated wild ginseng distilled herbal acupuncture groups were administered on A549 human lung cancer lines. Cell toxicity was carefully examined and from the analysis of DNA fragmentation, RT-PCR, and Western blot, manifestation of mRNA and proteins which are associated with apoptosis were inspected. Results : The following results were obtained on apoptosis of A549 human lung cancer lines after administering pH and electrolyte adjusted cultivated wild ginseng distilled herbal acupuncture. 1. Measuring cell toxicity of lung cancer cells, higher cell toxicity was detected at pH and electrolyte adjusted groups and the results were concentration dependent. 2. Through DNA fragmentation, we were able to confirm cell destruction in all groups. 3. Experiment groups treated with cultivated wild ginseng distilled herbal acupuncture showed inhibition of Bcl-2 and COX-2 at mRNA and Protein level, whileas increase of Bax was shown. 4. Manifestation of p21, p53, Cyclin E, and Cyclin D1 were confirmed in all groups. 5. Extrication of Cytochrome C was detected at all groups, as well as increased activity of the enzyme caspase-3 and caspase-9, and PARP fragmentation were confirmed. Conclusions : From the above results, we can carefully deduce cell destruction of A549 human lung cancer lines were induced by Apoptosis. At the same concentration level, cell destruction efficacy was better with adjusted pH and electrolyte. Cultivated wild ginseng distilled herbal acupuncture also showed decrease of Bcl-2 and COX-2, as well as increase of Bax. Since cultivated wild ginseng distilled herbal acupuncture increases manifestation of p21, p53, Cyclin E, and Cyclin D1, it affects cellular cycle and through these phenomena, we can consider extrication of Cytochrome C, increase of caspase, and PARP fragmentation are the results.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2002년도 학술대회지
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• pp.1-19
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• 2002

The use of herbals has increased considerably while their efficacy and safety remain untested. This unsupported surge in demand has prompted a call for their clinical evaluation. One area in which evaluations are emerging is ginseng and diabetes. Growing evidence is accumulating from in vitro and animal models indicating that various ginseng species, American (Panax quinquefolius L), Asian (Panax ginseng C.A. Meyer), Korean Red, San-chi (Panax notoginseng [Burk.] P.R. Chen), and the non-panax species Siberian (Eleutherococcus senticossus) ginsing, and their fractions, saponins (ginsenosides) and peptidoglycans (panaxans for panax species and eleutehrans for Siberian ginseng), might affect carbohydrate metabolism and related signaling molecules. Recent human studies from our laboratory have also shown a blood glucose lowering effect of American ginseng (AG) and some other ginseng spices postprandially after acute administration and chronically after administration for 8-weeks in people with type 2 diabetes. Although generally encouraging, these data only indicate a need for more evaluations of ginsengs safety and efficacy. Because of poor industry standardization, it is not known whether all ginsengs will affect blood glucose. In this regards some ginseng batches have demonstrated null effects while others have even raised postprandial glycemia. Clinical research should therefore focus on components involved in its glucose lowering effects.

• Journal of Ginseng Research
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• 제43권1호
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• pp.125-134
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• 2019

Background: Excessive stress causes varied physiological and psychological disorders including male reproductive problems. Here, we attempted to investigate the protective effects of Korean Red Ginseng (Panax ginseng Meyer; KRG) against sub-acute immobilization stress-induced testicular damage in experimental rats. Methods: Male rats (age, 4 wk; weight, 60-70 g) were divided into four groups (n = 8 in each group): normal control group, immobilization control group, immobilization group treated with 100 mg/kg of KRG daily, and immobilization group treated with 200 mg/kg of KRG daily. Normal control and immobilization control groups received vehicle only. KRG (100 mg/kg and 200 mg/kg) was mixed in the standard diet powder and fed daily for 6 mo. Parameters such as organ weight, blood chemistry, sperm kinematic values, and expression levels of testicular-related molecules were measured using commercially available kits, Western blotting, and reverse transcription polymerase chain reaction. Results: Data revealed that KRG restored the altered testis and epididymis weight in immobilization stress-induced rats significantly (p < 0.05). Further, KRG ameliorated the altered blood chemistry and sperm kinematic values when compared with the immobilization control group and attenuated the altered expression levels of spermatogenesis-related proteins (nectin-2, cAMP responsive element binding protein 1, and inhibin-${\alpha}$), sex hormone receptors (androgen receptor, luteinizing hormone receptor, and follicle-stimulating hormone receptor), and antioxidant-related enzymes (glutathione S-transferase m5, peroxiredoxin-4, and glutathione peroxidase 4) significantly in the testes of immobilization stress-induced rats. Conclusion: KRG protected immobilization stress-induced testicular damage and fertility factors in rats, thereby indicating its potential in the treatment of stress-related male sterility.

• Journal of Ginseng Research
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• 제35권3호
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• pp.352-359
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• 2011

Korean red ginseng (KRG) is used worldwide as a popular traditional herbal medicine. KRG has shown beneficial effects on cardiovascular diseases, such as atherosclerosis, diabetes, and hypertension. Up-regulation of a cytoprotective protein, heme oxygenase (HO)-1, is considered to augment the cellular defense against various agents that may induce cytotoxic injury. In the present study, we demonstrate that KRG water extract induces HO-1 expression in human umbilical vein endothelial cells (HUVECs) and possible involvement of the anti-oxidant transcription factor nuclear factor-eythroid 2-related factor 2 (Nrf2). KRG-induced HO-1 expression was examined by western blots, reverse transcriptase polymerase chain reaction and immunofluorescence staining. Specific silencing of Nrf2 genes with Nrf2-siRNA in HUVECs abolished HO-1 expression. In addition, the HO inhibitor zinc protoporphyrin blunted the preventive effect of KRG on $H_2O_2$-induced cell death, as demonstrated by terminal transferase dUTP nick end labeling assay. Taken together, these results suggest that KRG may exert a vasculoprotective effect through Nrf2-mediated HO-1 induction in human endothelial cell by inhibition of cell death.

• Journal of Ginseng Research
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• 제42권1호
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• pp.68-74
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• 2018

Background: Ginsenosides have been reported to have many health benefits, including anti-inflammatory effects, and the resolution of inflammation is now considered to be an active process driven by M2-type macrophages. In order to determine whether ginsenosides modulate macrophage phenotypes to reduce inflammation, 11 ginsenosides were studied with respect to macrophage polarization and the resolution of inflammation. Methods: Mouse peritoneal macrophages were polarized into M1 or M2 phenotypes. Reverse transcription-polymerase chain reaction, Western blotting, and measurement of nitric oxide (NO) and prostaglandin $E_2$ levels were performed in vitro and in a zymosan-induced peritonitis C57BL/6 mouse model. Results: Ginsenoside $Rg_3$ was identified as a proresolving ginseng compound based on the induction of M2 macrophage polarization. Ginsenoside $Rg_3$ not only induced the expression of arginase-1 (a representative M2 marker gene), but also suppressed M1 marker genes, such as inducible NO synthase, and NO levels. The proresolving activity of ginsenoside $Rg_3$ was also observed in vivo in a zymosan-induced peritonitis model. Ginsenoside $Rg_3$ accelerated the resolution process when administered at peak inflammatory response into the peritoneal cavity. Conclusion: These results suggest that ginsenoside $Rg_3$ induces the M2 polarization of macrophages and accelerates the resolution of inflammation. This finding opens a new avenue in ginseng pharmacology.

• Journal of Ginseng Research
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• 제34권4호
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• pp.369-375
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• 2010

This study evaluated the protective effects of ginseng leaf extract (GLE) against high fat-diet-induced hyperglycemia and hyperlipidemia, and explored the potential mechanism underlying these effects in C57BL/6J mice. The mice were randomly divided into four groups: normal control, high fat diet control (HFD), GLE-treated at 250 mg/kg, and GLE-treated at 500 mg/kg. To induce hyperglycemic and hyperlipidemic states, mice were fed a high fat diet for 6 weeks and then administered GLE once daily for 8 weeks. At the end of the treatment, we examined the effects of GLE on plasma glucose, lipid levels, and the expression of genes related to lipogenesis, lipolysis, and gluconeogenesis. Both GLE groups lowered levels of plasma glucose, insulin, triglycerides, total cholesterol, and non-esterified fatty acids when compared to those in HFD group. Histological analysis revealed significantly fewer lipid droplets in the livers of GLE-treated mice compared with HFD mice. To elucidate the mechanism, Western blots and RT-PCR were performed using liver tissue. Compared with HFD mice, GLE-treated mice showed higher levels of phosphorylation of AMP-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase, but no differences in the expression of lipogenic genes such as sterol regulatory element-binding protein 1a, fatty acid synthase, sterol-CoA desaturase 1 and glycerol-3-phosphate acyltransferase. However, the expression levels of lipolysis and fatty acid uptake genes such as peroxisome proliferator-activated receptor-$\alpha$ and CD36 were increased. In addition, phosphoenolpyruvate carboxykinase gene expression was decreased. These results suggest that GLE ameliorates hyperglycemia and hyperlipidemia by inhibiting gluconeogenesis and stimulating lipolysis, respectively, via AMPK activation.

• Journal of Ginseng Research
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• 제42권4호
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• pp.429-435
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• 2018

Background: Recent studies have shown that Korean Red Ginseng (KRG) successfully protects against dopaminergic neuronal death in the nigrostriatal pathway of a Parkinson's disease (PD) mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration; however, the mechanism has yet to be identified. Therefore, in this study we used two-dimensional electrophoresis to investigate the effects of KRG on the changes in protein expression in the substantia nigra (SN) of MPTP-treated mice. Methods: Male C57BL/6 mice (9 wk old) were intraperitoneally administered MPTP (20 mg/kg) four times at 2-h intervals, after which KRG (100 mg/kg) was orally administered once a day for 5 d. Two hours after the fifth KRG administration, a pole test was conducted to evaluate motor function, after which the brains were immediately collected. Survival of dopaminergic neurons was measured by immunohistochemistry, and protein expression was measured by two-dimensional electrophoresis and Western blotting. Results: KRG alleviated MPTP-induced behavioral dysfunction and neuronal toxicity in the SN. Additionally, the expression of eight proteins related to neuronal formation and energy metabolism for survival were shown to have changed significantly in response to MPTP treatment or KRG administration. KRG alleviated the downregulated protein expression following MPTP administration, indicating that it may enhance neuronal development and survival in the SN of MPTP-treated mice. Conclusion: These findings indicate that KRG may have therapeutic potential for the treatment of patients with PD.