• Journal of Ginseng Research
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• 제35권3호
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• pp.344-351
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• 2011

Ginsenoside $Rb_1$ is the main component in ginsenosides. It is a protopanaxadiol-type ginsenoside that has a dammarane-type triterpenoid as an aglycone. In this study, ginsenoside $Rb_1$ was transformed into gypenoside XVII, ginsenoside Rd, ginsenoside $F_2$ and compound K by glycosidase from Leuconostoc mesenteroides DC102. The optimum time for the conversion was about 72 h at a constant pH of 6.0 to 8.0 and the optimum temperature was about $30^{\circ}C$. Under optimal conditions, ginsenoside $Rb_1$ was decomposed and converted into compound K by 72 h post-reaction (99%). The enzymatic reaction was analyzed by highperformance liquid chromatography, suggesting the transformation pathway: ginsenoside $Rb_1$ ${\rightarrow}$ gypenoside XVII and ginsenoside Rd${\rightarrow}$ginsenoside $F_2{\rightarrow}$compound K.

• 생약학회지
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• 제45권1호
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• pp.1-10
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• 2014

Ginsenoside Rg3 (G-Rg3) is one of protopanaxadiol ginsenosides characteristic of red ginseng, steamed and dried ginseng (Panax ginseng), which has recently attracted much attention for its antitumor properties in vitro and in vivo animal models. Experimental studies have demonstrated that it could promote cancer cell apoptosis, inhibit cancer cell growth, the apoptosis of cancer cells, adhesion, invasion and metastasis, and also prevent an angiogenetic formation in prostate, breast, ovarian, colorectal, gastric, liver and lung cancer etc. It has shown the antitumor activities by modulation of diverse signaling pathways, including regulation of cell proliferation mediators (CDKs and cyclins), growth factors (vascular endothelial growth factor), tumor suppressors (p53 and p21), cell death mediators (caspases, Bcl-2, Bax), inflammatory response molecules ($NF-{\kappa}B$ and COX-2), protein kinases (JNK, Akt, and AMP-activated protein kinase) and Wnt/${\beta}$-catenin signaling. In addition, the combination of Rg3 and chemotherapeutic agents have synergistically enhanced therapeutic efficacy and reduced antagonistically side effects. Furthermore, it can reverse the multidrug resistance of cancer cells, prolong the survival duration and improve life quality of cancer patients. Taken together, accumulating evidences could provide the potential of G-Rg3 in the treatment of cancers and the feasibility of further randomized placebo controlled clinical trials.

• Journal of Microbiology and Biotechnology
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• 제32권7호
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• pp.902-910
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• 2022

The ginsenoside compound K (C-K) is widely used in traditional medicines, nutritional supplements, and cosmetics owing to its diverse pharmacological activities. Although many studies on C-K production have been conducted, fermentation is reported to produce C-K with low concentration and productivity. In the present study, addition of an inducer and optimization of the carbon and nitrogen sources in the medium were performed using response surface methodology to increase the C-K production via fermentation by Aspergillus tubingensis, a generally recognized as safe fungus. The optimized inducer and carbon and nitrogen sources were 2 g/l rice straw, 10 g/l sucrose, and 10 g/l soy protein concentrate, respectively, and they resulted in a 3.1-fold increase in the concentration and productivity of C-K (0.22 g/l and 1.52 mg/l/h, respectively) compared to those used before optimization without inducer (0.071 g/l and 0.49 mg/l/h, respectively). The feeding methods of American ginseng extract (AGE), including feeding timing, feeding concentration, and feeding frequency, were also optimized. Under the optimized conditions, A. tubingensis produced 3.96 mM (2.47 g/l) C-K at 144 h by feeding two times with 8 g/l AGE at 48 and 60 h, with a productivity of 17.1 mg/l/h. The concentration and productivity of C-K after optimization of feeding methods were 11-fold higher than those before the optimization (0.22 g/l and 1.52 mg/l/h, respectively). Thus, the optimization for the feeding methods of ginseng extract is an efficient strategy to increase C-K production. To our knowledge, this is the highest reported C-K concentration and productivity via fermentation reported so far.

• Preventive Nutrition and Food Science
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• 제15권2호
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• pp.105-112
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• 2010

Thirty-four strains of Lactobacillus species were isolated from soil and eight of these isolates (M1-4 and P1-4) were capable of growing on red ginseng agar. The M1 and P2 strains were determined to be L. plantarum and other strains (M2, M3, M4, P1, P3 and P4) were determined to be L. brevis. Fermentation of red ginseng extract (RGE) with strains M1, M2, P2 and P4 resulted in a low level of total carbohydrate content (174.3, 170.0, 158.8 and 164.8 mg/mL, respectively). RGE fermented by M3 showed a higher level of uronic acid than the control. The polyphenol levels in RGE fermented by M1, P1 and P2 (964.9, 941.7 and $965.3\;{\mu}g/mL$, respectively) were higher than the control ($936.8\;{\mu}g/mL$). Total saponin contents in fermented RGE (except M1) were higher than the control. RGE fermented by M2 and M3 had the highest levels of total ginsenosides (31.7 and 32.7 mg/mL, respectively). The levels of the ginsenoside Rg3 increased from 2.6 mg/mL (control) to 3.0 mg/mL (M2) or 3.1 mg/mL (M3). RGE fermented by M2 and M3 also had the highest levels of Rg5+Rk1 (7.7 and 8.3 mg/mL, respectively). Metabolite contents of ginsenoside (sum of CK, Rh1, Rg5, Rk1, Rg3 and Rg2) of M2 (13.0 mg/mL) and M3 (13.9 mg/mL) were also at a high level among the fermented RGE. Protopanaxadiol and protopanaxatriol content of ginsenoside of M2 (10.9 and 5.4 mg/mL, respectively) and M3 (11.0 and 5.7 mg/mL, respectively) were at higher levels than other fermented RGE.

• Molecules and Cells
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• 제19권1호
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• pp.137-142
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• 2005

We showed recently that ginsenosides inhibit the activity of various types of ion channel. Here we have investigated the role of the carbohydrate component of ginsenoside $Rg_3$ in the inhibition of $Na^+$ channels. The channels were expressed in Xenopus oocytes by injecting cRNAs encoding rat brain Nav1.2 ${\alpha}$ and ${\beta}1$ subunits, and analyzed by the two-electrode voltage clamp technique. Treatment with $Rg_3$ reversibly inhibited the inward $Na^+$ peak current ($I_{Na}$) with an $IC_{50}$ of $32.2{\pm}4.5{\mu}M$, and the inhibition was voltage-dependent. To examine the role of the sugar moiety, we prepared a straight chain form of the second glucose and a conjugate of this glucose with 3-(4-hydroxyphenyl) propionic acid hydrazide (HPPH). Neither derivative inhibited $I_{Na}$. Treatment with the carbohydrate portion of ginsenoside $Rg_3$, sophorose [${\beta}-D-glucopyranosyl$ ($1{\rightarrow}2$)-${\beta}-glucopyranoside$], or the aglycone (protopanaxadiol), on their own or in combination had no effect on $I_{Na}$. These observations indicate that the carbohydrate portion of ginsenoside $Rg_3$ plays an important role in its effect on the $Na^+$ channel.

• Journal of Ginseng Research
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• 제27권2호
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• pp.56-61
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• 2003

복강 내당능 시험과 MLD STZ 당뇨를 유발시킨 rat에서 백삼, 홍삼, 화기삼의 항당뇨 활성을 비교한 결과를 요약하면 다음과 같다. 1. 복강 내당능 시험에서 백삼은 효과를 나타내지 못한 반면 홍삼과 화기삼은 대조군에 대하여 유의적인 변차를 나타내었다. MLD STZ로 당뇨를 유발시킨 SD계 흰쥐에 백삼, 홍삼, 화기삼을 2주간 투여 후 혈당강하 활성을 비교한 결과 홍삼 투여군의 혈당이 가장 낮았으며 백삼과 화기삼은 비슷한 크기의 활성을 나타내었다. 2. 백삼과 홍삼, 화기삼은 모두 고혈당에 의한 체중 감소 현상을 개선시켰으며 각 투여군 간에는 유의적인 차이는 없었다. 3. 당뇨의 대표적인 증상인 다식 (多食)과 다음 (多飮)현상이 백삼, 홍삼, 화기삼 투여에 의하여 개선되었으며 그 중 홍삼에 의한 효과가 가장 컸다. 4. 혈당강하 활성과 ginsenoside profile간의 상관관계를 살펴본 결과 PPT/PPD ratio가 가장 큰 홍삼의 혈당강하 활성이 백삼과 화기삼에 비해 높은 것으로 보아 PPT/PPD ratio가 혈당강하 활성의 key ratio가 아닌가 추측된다.

• Journal of Ginseng Research
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• 제44권1호
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• pp.86-95
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• 2020

Background: Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure. Purpose: The present study aimed to elucidate the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects of Rb1 based on regulation of microflora. Methods: A pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 were compared between conventional and PGF rats. The relative abundances of common probiotics were quantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressions of the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (α2, β2, and γ2) and GABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/R+Rb1 rat hippocampus and striatum were assessed to reveal the neuroprotective mechanism of Rb1. Results: The results showed that microbiota plays a key role in neuroprotection of Rb1. The relative abundance of Lactobacillus helveticus (Lac.H) increased 15.26 fold after pretreatment with Rb1. I/R surgery induced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were prevented by colonizing the rat gastrointestinal tract with Lac.H (1 × 10⁹ CFU) by gavage 15 d before I/R surgery. Both Rb1 and Lac.H upregulated expression of GABA receptors in I/R rats. Coadministration of a GABA_A receptor antagonist significantly attenuated neuroprotective effects of Rb1 and Lac.H. Conclusion: In sum, Rb1 exerts neuroprotective effects by regulating Lac.H and GABA receptors rather than through direct distribution to the target sites.

• 한국식품과학회지
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• 제50권3호
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• pp.349-355
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• 2018

본 연구에서는 상처치유(wound healing)와 같은 허혈성 심뇌혈관 질환의 잠재적 치료제로서 산양삼 추출물과 진세노사이드 Rg5의 가능성을 인간 제대정맥 내피세포인 HUVEC에서 확인하고자 하였다. 그 결과, 산양삼 추출물과 Rg5는 10-100 nM의 저농도에서 혈관신생 과정에서 발생하는 세포의 증식이나 이동, 관 형성과정을 유의적으로 증진시켰으며, 그 증가현상은 산양삼 추출물과 Rg5가 유사한 수준으로 발생하였다. 따라서 Rg5를 이용하여 혈관신생 과정에 관여하는 신호전달 메커니즘을 확인한 결과, Akt/eNOS와 ERK1/2의 인산화는 양성대조군으로 사용한 VEGF와 유사한 수준으로 증가되는 것을 확인하였다. 마지막으로 혈관 신생 유도인자이며 양성대조군인 VEGF의 혈관염증 관련 부작용이 Rg5의 혈관신생 효과에도 작용하는지 확인하기 위하여 혈관염증 관련 단백질인 ICAM-1과 VCAM-1의 발현량을 확인한 결과, ICAM-1과VCAM-1의 발현이 양성대조군인 VEGF에서는 유의적으로 증가하였으나 Rg5를 처리한 경우에는 일반 대조군과 유사한 수준으로 낮게 나타났다. 따라서 본 연구는 산양삼 추출물과 Rg5가 혈관신생 유도효과가 있으며, 이러한 현상은 Akt/eNOS와 ERK 관련 신호전달 메커니즘을 통해 진행되고 이러한 효과가 혈관염증은 유도하지 않는다는 것을 입증하였으며, 잠재적 치료제로서의 가능성을 확인하는 계기가 되었다.

• Journal of Ginseng Research
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• 제45권2호
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• pp.228-235
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• 2021

Backgroud: Ginsenoside compound K (GK) is a major metabolite of protopanaxadiol-type ginsenosides and has remarkable anticancer activities in vitro and in vivo. This work used an ionic cross-linking method to entrap GK within O-carboxymethyl chitosan (OCMC) nanoparticles (Nps) to form GK-loaded OCMC Nps (GK-OCMC Nps), which enhance the aqueous solubility and stability of GK. Methods: The GK-OCMC Nps were characterized using several physicochemical techniques, including x-ray diffraction, transmission electron microscopy, zeta potential analysis, and particle size analysis via dynamic light scattering. GK was released from GK-OCMC Nps and was conducted using the dialysis bag diffusion method. The effects of GK and GK-OCMC Nps on PC3 cell viability were measured by using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Fluorescent technology based on Cy5.5-labeled probes was used to explore the cellular uptake of GK-OCMC Nps. Results: The GK-OCMC NPs had a suitable particle size and zeta potential; they were spherical with good dispersion. In vitro drug release from GK-OCMC NPs was pH dependent. Moreover, the in vitro cytotoxicity study and cellular uptake assays indicated that the GK-OCMC Nps significantly enhanced the cytotoxicity and cellular uptake of GK toward the PC3 cells. GK-OCMC Nps also significantly promoted the activities of both caspase-3 and caspase-9. Conclusion: GK-OCMC Nps are potential nanocarriers for delivering hydrophobic drugs, thereby enhancing water solubility and permeability and improving the antiproliferative effects of GK.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2007년도 춘계 학술대회
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• pp.23-24
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• 2007

Purpose: 인삼이 항당뇨 활성을 가진다는 연구가 많은 연구자들에 의해 진행되었고, 이는 인삼의 구성 성분 중 ginsenoside에 기인한다는 보고가 있다. 본 연구는 ginsenoside의 항당뇨 작용기전을 in vitro에서 알아보고자 3T3-L1 지방세포에서 glucose uptake와 췌장 베타세포인 HIT-T15 세포에서 insulin 분비 효과를 확인하였다. 이를 위하여 인삼을 식초로 처리한 긴삼의 70% MeOH 분획으로부터 protopanaxadiol 계인 ginsenoside $Rb_2$, $Rg_3$ 그리고 protopanaxtriol 계인 $Rg_2$를 분리하여 본 실험에 사용하였다. Method: Ginsenoside $Rb_2$, $Rg_2$, $Rg_3$가 지방 세포에서 glucose uptake에 미치는 효과를 확인하기 위하여 3T3-L1 세포를 DMEM (Dulbecco's Modified Eagle's Medium) 배지에서 분화 유도시켰으며 3T3-L1 preadipocyte가 80% 정도 자라면 분화 유도 배지 (5% fetal bovine serum (FBS), 0.5 mM isobutylmethylxanthine (IBMX), 1 mM dexamethasone 그리고 $10{\mu}g/ml$ insulin가 포함된 DMEM)로 4일, $10{\mu}g/ml$ insulin가 포함된 DMEM으로 2일, FBS만 포함된 DMEM으로 2일 배양하여 총 8일 동안 분화를 유도하였다. 분화 유도된 3T3-L1 adipocytes 에 각각 $Rb_2$, $Rg_2$, $Rg_3$를 $20{\mu}M$로 처리하여 16시간 배양하여 low glucose DMEM에서 3시간 배양한 후에 $37^{\circ}C$에서 insulin 10 ng/ml 과 각각 $Rb_2$, $Rg_2$, $Rg_3$가 포함된 Krebs Ringer Hepes buffer(KRP buffer)에서 20분간 배양하였다. 2-deoxy-D-[$^3H$]-glucose를 넣고 10분 후에 차가운 PBS로 반응을 종결시켜 lysis buffer로 cell을 모은 후 scintillation counter를 이용하여 glucose를 측정하였다. Insulin 분비 효과는 HIT-T15 세포와 일차 배양한 흰쥐 소도세포(islets)를 사용하여 확인하였다. HIT-T15 세포는 24 well plate에 well 당 $2{\times}10^5$ 개씩 분주하여 24시간 동안 배양한 후 시료를 처리하였으며 소도 세포는 Sprague-Dawley rat의 췌장에 collagenase가 포함된 Hanks' Balanced Salt Solution(HBSS)을 주입하여 분리하고 islets을 얻었다. 분리한 소도세포를 $1{\sim}2$일 동안 배양하여 $Rb_2$, $Rg_2$, $Rg_3$가 각각 $20{\mu}M$의 농도로 첨가된 insulin 측정용 buffer인 Krebs-Ringer buffer (KRB+0.3% BSA, KRBB)에 $37^{\circ}C$에서 1시간 incubation 시킨 후 배양액으로 분비된 인슐린의 양을 측정하였다. 한편 ginsenoside의 인슐린 분비 촉진 기전을 알아보기 위한 실험에서는 ATP-sensitive $K^+$ channel opener인 diazoxide (0.5 mM)가 ginsenoside에 의해 촉진된 인슐린 분비를 억제하는지 살펴보았다. Result: glucose uptake assay 에서는 $Rg_2$가 가장 크게 glucose uptake를 증가시켰고 $Rb_2$, $Rg_3$는 그 활성이 크지 않았다. 한편 Insulin 분비 효과는 diol계인 $Rg_3$에서 용량 의존적으로 인슐린의 분비를 촉진시켰으며 $20{\mu}M$ 농도에서 대조군과 비교해 1.5배 이상의 분비 촉진 효과를 보였고 triol계인 $Rg_2$ 에서는 이러한 효과가 나타나지 않았다. $Rg_3$의 인슐린 분비 촉진 기전을 0.5 mM 의 diazoxide를 이용하여 확인한 결과 $Rg_3$에 의해 촉진된 인슐린 분비를 감소시켰다. 이로 미루어보아 $Rg_3$의 인슐린 분비 촉진 기전은 ATP-sensitive $K^+$ 채널의 봉쇄에 의한 것임을 확인할 수 있었다.