• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2011년도 추계학술발표회
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• pp.31-45
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• 2011

The amyloid ${\beta}$-peptide ($A{\beta}$), which originates from the proteolytic cleavage of amyloid precursor protein (APP), plays a central role in the pathogenesis of Alzheimer's disease (AD). Mounting evidence indicates that different species of $A{\beta}$, such as $A{\beta}$ oligomers and fibrils, may contribute to AD pathogenesis via distinct mechanisms at different stages of the disease. Importantly, elevation and accumulation of soluble $A{\beta}$ oligomers closely correlate with cognitive decline and/or disease progression in animal models of AD. In agreement with these studies, oligomers of $A{\beta}$ have been shown to directly affect synaptic plasticity, a neuronal process that is known to be essential for memory formation. Our previous studies showed that $A{\beta}$ induces the breakdown of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a phospholipid that regulates key aspects of neuronal function. PI(4,5)P2 breakdown was found to be a key step toward synaptic and memory dysfunction in a mouse model of AD. To this end, we seek to identify small molecules that could elevate the levels of PI(4,5)P2 and subsequently block $A{\beta}$ oligomer-induced breakdown of PI(4,5)P2 and synaptic dysfunction.. We found that (20S)Rg3, an active triterpene glycoside from heat-processed ginseng, serves as an agonist for phosphatidylinositol 4-kinase IIalpha (PI4KIIalpha), which is a lipid kinase that mediates a rate-limiting step in PI(4,5)P2 synthesis. Consequently, (20S)Rg3 stimulates PI(4,5)P2 synthesis by directly stimulating the activity of PI4KIIalpha. Interestingly, treatment of a mouse model of AD with (20S)Rg3 leads to reversal of memory deficits. Our data suggest that the PI(4,5)P2-promoting effects of (20S)Rg3 may help mitigate the cognitive symptoms associated with AD.

• Journal of Ginseng Research
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• 제40권2호
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• pp.105-112
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• 2016

Background: Minor saponins or human intestinal bacterial metabolites, such as ginsenosides Rg3, F2, Rh2, and compound K, are more pharmacologically active than major saponins, such as ginsenosides Rb1, Rb2, and Rc. In this work, enzymatic hydrolysis of ginsenoside Rb1 was studied using enzyme preparations from cultured mycelia of mushrooms. Methods: Mycelia of Armillaria mellea, Ganoderma lucidum, Phellinus linteus, Elfvingia applanata, and Pleurotus ostreatus were cultivated in liquid media at $25^{\circ}C$ for 2 wk. Enzyme preparations from cultured mycelia of five mushrooms were obtained by mycelia separation from cultured broth, enzyme extraction, ammonium sulfate (30-80%) precipitation, dialysis, and freeze drying, respectively. The enzyme preparations were used for enzymatic hydrolysis of ginsenoside Rb1. Results: Among the mushrooms used in this study, the enzyme preparation from cultured mycelia of A. mellea (AMMEP) was found to convert ginsenoside Rb1 into compound K with a high yield, while those from G. lucidum, P. linteus, E. applanata, and P. ostreatus produced remarkable amounts of ginsenoside Rd from ginsenoside Rb1. The enzymatic hydrolysis pathway of ginsenoside Rb1 by AMMEP was $Rb1{\rightarrow}Rd{\rightarrow}F2{\rightarrow}$ compound K. The optimum reaction conditions for compound K formation from ginsenoside Rb1 were as follows: reaction time 72-96 h, pH 4.0-4.5, and temperature $45-55^{\circ}C$. Conclusion: AMMEP can be used to produce the human intestinal bacterial metabolite, compound K, from ginsenoside Rb1 with a high yield and without food safety issues.

• 한국식품조리과학회지
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• 제26권4호
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• pp.475-480
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• 2010

인삼과 팽화홍삼은 인삼의 가공방법에 따라 구분되어지며, 가공처리과정중 인삼의 효능을 나타내는 사포닌 함량의 변화가 생긴다. 본 연구에서는 인삼과 팽화홍삼을 이용하여 마우스 대식세포인 RAW 264.7세포에서 LPS에 의한 염증에 대한 항염 효과와 그 기전을 규명하고자 하였다. 본 연구를 통해서 인삼과 팽화홍삼 모두 LPS에 의한 NO의 생성을 억제시키는 것을 확인하였으며, TNF-$\alpha$ 및 INF-$\gamma$의 생성 또한 억제시키는 것을 알 수 있었다. 인삼과 팽화홍삼 모두 COX-2의 발현 및 LPS에 의한 $I{\kappa}B$의 인산화를 억제시킴으로써 NF-${\kappa}B$의 활성을 억제시키는 것임을 알 수 있었으나 인삼에 비하여 팽화홍삼의 항염 효과가 더욱 높았다. 그러므로 팽화홍삼이 인삼에 비하여 NO의 생성을 더 효과적으로 억제시키는 것은 팽화가공을 통하여 특정 진세노사이드($Rb_1,\;Rg_5+Rk_1$)의 증가에 의한 것으로 추정된다.

• Journal of Ginseng Research
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• 제34권3호
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• pp.227-236
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• 2010

The objective of this study was to evaluate the potential use of ginseng leaf as a cosmetic material. In this research, we employed enzymatic treated ginseng leaf by using Ultraflo L to improve the recovery of ginsenosides from the ginseng leaf and studied the biological activities and skin safety of the enzymatic treated ginseng leaf for use as a cosmetic material. The total ginsenoside contents of the non-enzymatic treated ginseng leaf (NEGL) and Ultraflo L treated ginseng leaf (UTGL) were 271 and 406 mg/g, respectively. The level of metabolite ginsenosides (sum of Rg2, Rg3, Rg5, Rk1, compound K, Rh1, Rh2, and F2) was higher in UTGL (93.1 mg) compared to NEGL (62.4 mg) in one gram ginseng leaf extract. The increase in amounts of ginsenoside types in UTGL compared to NEGL was generally 140% to 157%. UTGL exhibited relatively higher 2,2-diphenyl-2-picrylhydrazyl hydrate ($IC_{50}$, 2.8 mg/mL) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt ($IC_{50}$, 1.6 mg/mL) radical scavenging activities compared to NEGL (4.8 mg/mL and 2.2 mg/mL). The UTGL group showed normalized hydrogen peroxide, lipid peroxidation and visual wrinkling grade induced-UVB exposure. The UTGL did not induce any adverse reactions such as erythema and edema on intact skin sites; however, some guinea pigs treated with UTGL on abraded skin sites showed very slight erythema. The primary irritation index (PII) score of UTGL was 0.05 and it was classified as a practically non-irritating material (PII, 0 to 0.5). In skin sensitization tests with guinea pigs, UTGL had a positive rate of skin sensitization at 40%, and the mean evaluation score was 0.4.

• Molecules and Cells
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• 제27권5호
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• pp.591-599
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• 2009

Nicotinic acetylcholine receptors (nAChRs) play important roles in nervous system functions and are involved in a variety of diseases. We previously demonstrated that ginsenosides, the active ingredients of Panax ginseng, inhibit subsets of nAChR channel currents, but not ${\alpha}7$, expressed in Xenopus laevis oocytes. Mutation of the highly conserved Leu247 to Thr247 in the transmembrane domain 2 (TM2) channel pore region of ${\alpha}7$ nAChR induces alterations in channel gating properties and converts ${\alpha}7$ nAChR antagonists into agonists. In the present study, we assessed how point mutations in the Leu247 residue leading to various amino acids affect 20(S)-ginsenoside $Rg_3$ ($Rg_3$) activity against the ${\alpha}7$ nAChR. Mutation of L247 to L247A, L247D, L247E, L247I, L247S, and L247T, but not L247K, rendered mutant receptors sensitive to $Rg_3$. We further characterized $Rg_3$ regulation of L247T receptors. We found that $Rg_3$ inhibition of mutant ${\alpha}7$ nAChR channel currents was reversible and concentration-dependent. $Rg_3$ inhibition was strongly voltage-dependent and noncompetitive manner. These results indicate that the interaction between $Rg_3$ and mutant receptors might differ from its interaction with the wild-type receptor. To identify differences in $Rg_3$ interactions between wild-type and L247T receptors, we utilized docked modeling. This modeling revealed that $Rg_3$ forms hydrogen bonds with amino acids, such as Ser240 of subunit I and Thr244 of subunit II and V at the channel pore, whereas $Rg_3$ localizes at the interface of the two wild-type receptor subunits. These results indicate that mutation of Leu247 to Thr247 induces conformational changes in the wild-type receptor and provides a binding pocket for $Rg_3$ at the channel pore.

• 한국식품과학회지
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• 제35권5호
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• pp.1003-1006
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• 2003

시중에서 유통되고 있는 건조인삼제품인 백삼, 홍삼, 태극삼의 품질을 인삼산업법과 한국산업규격 등 국내 규격과 관련하여 조사하였다. 모든 제품이 일반품질기준인 수분함량 14.0% 이하, 회분함량 5.0% 이하, 물포화 n-부탄올 추출물함량 2.0% 이상에 적합하였다. 고려인삼의 유효성분인 진세노사이드 $Rb_1$, Rf, $Rg_1$도 HPLC 분석결과 관찰되었다. 그러나 홍삼제품을 제외하고는 단위포장내 개체중량의 균일성이 거의 지켜지지 않고 있는 것으로 나타났다.

• Journal of Ginseng Research
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• 제30권1호
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• pp.1-7
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• 2006

Ceramide has been involved in celt death and acted as a lipid mediator of stress responses. Elevation of ceramide level was reported to occur in oxidative stress and lead to cell death in many cell types. This study was undertaken to elucidate a protective role of ginsenoside Rgl in cell death induced by oxidative stress. When LLC-PK1 cells were treated with $H_2O_2$ at a concentration of $400{\mu}M$ for 5 hr, cell death was observed and a released LDH activity indicative of cytotoxicity was Increased. $H_2O_2$ exposure to LLC-PK1 cells was shown to elevate the content of total ceramide by approximately 200% compared to control cells. Ceramide level was hypothesized to be a key to a reversal of cell death to survival. Ginsenoside Rgl at the concentrations ranging from 12.5 to $250{\mu}M$ protected LLC-PK1 cells from cell death induced by $H_2O_2\;at\;400{\mu}M$ for 5 hr, and decreased the ceramide level relative to $H_2O_2$. Ginsenoside Rgl inhibited neutral human ceramidase by 71% of controls, while sphingomyelinase was not inhibited. These results suggest that ginsenoside Rgl show the protection against cell death via the modulation of ceramide metabolism, and ceramide may be a promising therapeutic target for human diseases related to cell death.

• 한국식품영양과학회지
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• 제45권12호
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• pp.1740-1746
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• 2016

본 연구는 산양삼의 이용가치를 높이고, 기능성 식품소재 개발을 위하여 산양삼의 이화학적 특성과 추출용매를 달리하여 추출한 각각의 추출물의 항산화 활성을 비교하였다. 산양삼의 일반성분은 수분 7.56%, 탄수화물 73.01%, 단백질 12.58%, 지질 1.99%, 회분 5.54%를 나타내었고, 총아미노산 함량은 16.17 mg/100 g이었으며, 그중 필수아미노산은 1.42 mg/100 g을 나타내었다. 총 ginsenoside 함량은 15.98 mg/g을 나타내었고, 그중 major ginsenoside($Rb_1$, $Rb_2$, $Rb_3$, Rc, Rd, Re, Rf, $Rg_1$)의 함량은 15.94 mg/g, minor ginsenoside($Rg_3$, $Rh_1$, $Rh_2$) 함량은 0.04 mg/g을 나타내었다. 1 mg/mL 농도로 조정한 증류수를 이용한 산양삼 추출물(KGW), 70% 에탄올을 이용한 산양삼 추출물(KGE)의 항산화 활성을 측정한 결과 KGE가 모든 항목에서 가장 높게 활성을 나타냈으며, 각각 8.93 mg/g(총폴리페놀 함량), 3.96 mg/g(총플라보노이드 함량), 57.57%(DPPH 라디칼 소거능), 70.73%(ABTS 라디칼 소거능), 44.12%(아질산염 소거능), 78.05%(SOD 유사활성), $1.08O.D_{700nm}$(환원력), 55.33%(ferrous ion chelating activity)를 나타내었다. 또한, 각각의 산양삼 추출물의 elastase, collagenase 및 tyrosinase 저해활성을 측정한 결과 역시 KGE가 모든 항목에서 가장 높은 활성을 나타내었으며, 각각 81.96%, 78.96%, 30.96%를 나타내었다.

• Journal of Ginseng Research
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• 제29권1호
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• pp.1-18
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• 2005

인삼(Panax ginseng C.A. Meyer)은 가공방법fl 따라 크게 백삼과 홍삼으로 분류된다. 가공 공정 면에서 홍삼은 생 인삼(수삼)을 그대로 건조한 백삼과는 다르게 일정한 온도조건 하에서 수증기로 쪄서 건조 한 인삼으로 두 종류의 인삼간에는 열처리 공정에 차이점이 있다. 품질 안정성 면에서 홍삼은 열처리과정에서 효소의 불 활성화와 자체 항산화 물질의 증가로 저장성이 양호하고, 호화전분이 되어 끓일 때 내용성분이 잘 우러나오고 소화 흡수도 양호한 것으로 여겨진다. 성분 면에서 홍삼제조 시 열처리(steaming처리)와 가수분해 반응에 의해 화학성분의 구조적 변환이 일어나 홍삼특유의 암세포증식억제 활성 성분인 $ginsenosides-Rh_2,\;-Rh_4,\;-Rs_3,\;-Rs_4,\;-Rg_5$, 암세포 전이 억제 및 혈관확장 효과 등을 나타내는 $ginsenoside-Rg_3$ 등이 생성된다는 것이 밝혀졌다. 또한 비사포닌계 생리활성물질로 암세포 증식억제 활성을 가진 polyacetylenic alcobol의 구조적 변환에 의해 panaxytriol 등이 생성되고, 그리고 maillard 반응 생성물로 항산화 활성 성분인 maltol과 당과 아미노산이 결합된 아미노산 유도체인 arginyl-fructsyl-glucose등이 생성된다. 한편 홍삼과 백삼 및 이들 제품의 수출과 관련하여 각 수출 대상국의 진세노사이드 수준의 품질관리기준에 대한 충분한 분석화학적 정보의 확보가 필요하며, 금후 이에 적합한 품질기준의 설정 보완이 필요할 것이다. 특히 홍삼의 경우 찌는 온도와 시간의 장단에 따라, 또는 그 농축액 제조 시 추출 및 농축 조건(온도와 시간)에 따라 인삼의 품질 지표 성분으로 이용되고 있는 ginsenosides를 비롯한 상당한 성분의 변환이 일어날 수 있으므로 이를 고려한 품질관리방법의 고안이 필요할 것으로 사료된다. 효능 면에서 홍삼과 백삼의 차별성에 대해서는 in vitro 혹은 in vivo 시험에서 노화억제효과와 관련된 항산화 활성을 비롯해서 혈액순환개선 효과, 암 발생 억제력 등의 약리 활성이 홍삼이 백삼보다 상대적으로 우수한 것으로 보고되었다. 아울러 한방의학에서 일반적으로 허를 보 하는 힘은 홍삼이 강한 것으로 인식되고 있다. 그러나 아직 실제 임상실험에 의한 비교 평가는 미흡한 실정이며, 특히 경구투여 후 체내 동태측면에서 그 효과의 차별성에 대한 연구는 거의 이루어지지 않았다. 금후 홍삼과 백삼의 효과 우열의 측면이 아닌 그 용도와 적응증에 차이가 있는지에 초점을 맞추어 보다 과학적 평가가 이루어져야 할 것이다. 결론적으로 가능한 동일한 재배조건에서 생산된 원료수삼으로 제조된 홍삼과 백삼의 원 생약과 그 추출 분획물, 또는 성분을 시료로 하여 화학성분 조성을 비교하고 이와 연계한 실험적 효능연구의 확충과 특히 임상적 효능 비교연구를 통해 과연 그 적응증에 차이가 있는지에 대한 보다 많은 과학적 검토가 이루어져야 할 것이다.

• 대한한의학회지
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• 제33권3호
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• pp.200-230
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• 2012

Objectives: Ginseng, Panax ginseng C. A., white ginseng, has been used for thousands of years in Traditional Korean Medicine. Red ginseng can be made by a steaming process of white ginseng changing a variety of ginsenosides and ingredients such as dencichine. This article reviews red ginseng for mechanisms for pharmacodynamics and toxicity based on the content of ginseng's active ingredients, ginsenoside changed by steaming. Methods: The following electronic databases were searched: PubMed, Science Direct and Chinese Scientific Journals full text database (CQVIP), and KSI (Korean Studies Information) from their respective inceptions to June 2012. Results: Compared with unsteamed ginseng, the content of ginsenosides Rg2, Rg3, Rg5, Rh1, Rh2 and Rk1 called red ginseng-specific ginsenosides increased after the steaming process. Different ginsenosides have shown a wide variety of effects such as lowering or raising blood sugar and blood pressure or stimulating or sedating the nervous system. Especially, the levels of Rg2, Rg3, Rg5, Rh1, Rh2 and Rk1 were increased by the steaming process, showing a variety of pharmacodynamics in biological systems. Also, various processing methods such as puffing and fermentation have been developed in processing crude ginseng or red ginseng, affecting the content of ginseng's ingredients. The safety issue could be the most critical, specifically, on changed ginseng's ingredients such as dencichine. The level of dencichine was significantly reduced in red ginseng by the steaming process. In addition, the possible toxicity for red ginseng was affected by cytochrome P450, a herbal-drug interaction. Conclusions: The variety of pharmacological and toxicological properties should be changed by steaming process of Panax ginseng C. A., white ginseng. Even if it is not sure whether the steaming process of white ginseng would be better pharmacologically, it is sure that steaming reduces the level of dencichine causing a lower toxicity to the nervous system.