• Journal of Ginseng Research
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• 제45권4호
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• pp.473-481
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• 2021

Background: Mitochondrial dysfunction is one of the significant reasons for Alzheimer's disease (AD). Ginsenosides, natural molecules extracted from Panax ginseng, have been demonstrated to exert essential neuroprotective functions, which can ascribe to its anti-oxidative effect, enhancing central metabolism and improving mitochondrial function. However, a comprehensive analysis of cellular mitochondrial bioenergetics after ginsenoside treatment under Aβ-oxidative stress is missing. Methods: The antioxidant activities of ginsenoside Rb₁, Rd, Re, Rg₁ were compared by measuring the cell survival and reactive oxygen species (ROS) formation. Next, the protective effects of ginsenosides of mitochondrial bioenergetics were examined by measuring oxygen consumption rate (OCR) in PC12 cells under Aβ-oxidative stress with an extracellular flux analyzer. Meanwhile, mitochondrial membrane potential (MMP) and mitochondrial dynamics were evaluated by confocal laser scanning microscopy. Results: Ginsenoside Rg₁ possessed the strongest anti-oxidative property, and which therefore provided the best protective function to PC12 cells under the Aβ oxidative stress by increasing ATP production to 3 folds, spare capacity to 2 folds, maximal respiration to 2 folds and non-mitochondrial respiration to 1.5 folds, as compared to Aβ cell model. Furthermore, ginsenoside Rg1 enhanced MMP and mitochondrial interconnectivity, and simultaneously reduced mitochondrial circularity. Conclusion: In the present study, these results demonstrated that ginsenoside Rg₁ could be the best natural compound, as compared with other ginsenosides, by modulating the OCR of cultured PC12 cells during oxidative phosphorylation, in regulating MMP and in improving mitochondria dynamics under Aβ-induced oxidative stress.

• Mass Spectrometry Letters
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• 제7권4호
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• pp.106-110
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• 2016

Ginseng, a traditional herbal drug, has been used in Eastern Asia for more than 2000 years. Various ginsenosides, which are the major bioactive components of ginseng products, have been shown to exert numerous beneficial effects on the human body when co-administered with drugs. However, this may give rise to ginsenoside-drug interactions, which is an important research consideration. In this study, acassette assay was performed the inhibitory effects of 12 ginsenosides on seven cytochrome P450 (CYP) isoforms in human liver microsomes (HLMs) using LC-MS/MS to predict the herb-drug interaction. After incubation of the 12 ginsenosides with seven cocktail CYP probes, the generated specific metabolites were quantified by LC-MS/MS to determine their activities. Ginsenoside Rb1 and F2 showed strong selective inhibitory effect on CYP2C9-catalyzed diclofenac 4'-hydroxylation and CYP2B6-catalyzed bupropion hydroxylation, respectively. Ginsenosides Rd showed weak inhibitory effect on the activities of CYP2B6, 2C9, 2C19, 2D6, 3A4, and compound K, while ginsenoside Rg3 showed weak inhibitory effects on CYP2B6. Other ginsenosides, Rc, Rf, Rg1, Rh1, Rf, and Re did not show significant inhibitory effects on the activities of the seven CYPs in HLM. Owing to the poor absorption of ginsenosides after oral administration in vivo, ginsenosides may not have significant side effects caused by interaction with other drugs.

• 한국식품저장유통학회지
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• 제20권4호
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• pp.573-582
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• 2013

본 연구에서는 ${\beta}$-glucosidase 활성이 있는 유산균주를 이용하여 발효인삼의 ginsenoside 유용 유도체의 전환 검토 및 품질특성 알아보고자 하였다. ${\beta}$-glucosidase 활성 유산균주를 검색하여 인삼 및 홍삼 발효에 따른 TLC 패턴, ginsenoside 함량 변화, 총 페놀성 화합물 함량, 전자공여능 및 총당 함량을 분석하였다. $37^{\circ}C$에서 65시간 발효 후 Rg2r, Rh2s, Rh2r은 모두 불검출되었으며, 인삼 및 홍삼 추출물 발효에서 발효전과 비교하여 Rg1, Re는 감소한 반면, Rh1, Rg2s, Rd, Rg3r, Rg3s는 발효 후 모두 증가한 것으로 나타났다. 홍삼에서 대표적인 성분으로 알려져 있는 Rg3의 경우 홍삼액 발효전 $104.56{\mu}g/mL$에서 발효 후 균주 종류에 따라 $114.83{\sim}131.68{\mu}g/mL$으로 증가하였다. 7일간 발효 후 홍삼액의 총 페놀성 화합물 및 전자공여능은 일부 균주에서는 발효전과 비교하여 감소하다가 다시 증가하는 경향을 나타내기도 하였으나, 발효가 0~7일차까지 진행됨에 따라 전반적으로 약간 감소되는 경향을 나타내었다. 전자공여능은 인삼 추출물 발효액은 발효 후 균주 종류에 따라 증가하는 경향을 보였으나, 홍삼 추출액은 발효 후 낮아지는 경향을 보였다. 인삼 및 홍삼 추출액을 첨가하여 유산균주별로 발효를 실시한 결과 총당 함량은 발효에 따라 감소하는 것으로 나타났다.

• Biotechnology and Bioprocess Engineering:BBE
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• 제10권2호
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• pp.162-165
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• 2005

A series of fluorine and hydroxyl containing jasmonate derivatives, which were chemically synthesized in our institute, were investigated for their effects on the biosynthesis and heterogeneity of ginsenosides in suspension cultures of Panax notoginseng cells. Com-pared to the control (without addition of elicitors), $100{\mu}M$ of each of the jasmonate was added on day 4 to the suspension cultures of P. notoginseng cells. It was observed that, jasmonates greatly enhanced the ginsenoside content and the ratio of Rb group to Rg group (i.e. $(Rb_1\;+\;Rd)/(Rg_1\;+\;Re)$ in the P. notoginseng cells. Some of the synthetic jasmonates, such as pentafluoropropyl jasmonate (PFPJA), 2-hydroxyethyl jasmonate (HEJA) and 2-hydroxye-thoxyethyl jasmonate (HEEJA), could promote the ginsenoside content to $2.55\;\pm\;0.11,\;3.65\;\pm\;0.13\;and\;2.94\;\pm\;0.06$mg/100 mg DW, respectively, compared to that of $0.64\;\pm\;0.06$mg/100 mg DW for the control and $2.17\;\pm\;0.04$ mg/100 mg DW by the commercially available methyl jasmonate (MJA); and they could change the respective Rb:Rg ratio to $1.60\;\pm\;0.04,\;1.87\;\pm\;0.01\;and\;1.56\;\pm\;0.05$, compared to that of $0.47\;\pm\;0.01$ for the control and $1.42\;\pm\;0.06$ by MJA. The results suggest that suitable esterification of MJA with fluorine or hydroxyl group could in-crease the elicitation activity to induce plant secondary metabolism. The information obtained from this study is useful for hyper-production of heterogeneous products by plant cell cultures.

• Journal of Ginseng Research
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• 제37권3호
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• pp.332-340
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• 2013

In this study, gamma rays were used to irradiate embryogenic calli induced from cotyledon explants of Panax ginseng Meyer. After the embryogenic calli were irradiated, they were transferred to adventitious roots using an induction medium; next, mutated adventitious root (MAR) lines with a high frequency of adventitious root formations were selected. Two MAR lines (MAR 5-2 and MAR 5-9) from the calli treated with 50 Gy of gamma rays were cultured on an $NH_4NO_3$-free Murashige and Skoog medium with indole-3-butyric acid 3 mg/L. The expression of genes related to ginsenoside biosynthesis was analyzed using reverse transcription polymerase chain reaction with RNA prepared from native ginseng (NG), non-irradiated adventitious root (NAR) and 2 MAR lines. The expression of the squalene epoxidase and dammarenediol synthase genes was increased in the MAR 5-2 line, whereas the phytosterol synthase was increased in the MAR 5-9 line. The content and pattern of major ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1) were analyzed in the NG, NAR, and 2 MAR lines (MAR 5-2 and MAR 5-9) using TLC and HPLC. In the TLC analysis, the ginsenoside patterns in the NG, NAR, and 2 MAR lines were similar; in contrast, the MAR 5-9 line showed strong bands of primary ginsenosides. In the HPLC analysis, compared with the NG, one new type of ginsenoside was observed in the NAR and 2 MAR lines, and another new type of ginsenoside was observed in the 2 MAR lines irradiated with gamma rays. The ginsenoside content of the MAR 5-9 line was significantly greater in comparison to the NG.

• 한국미생물·생명공학회지
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• 제50권3호
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• pp.395-403
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• 2022

본 연구에서는 한국형 프로바이오틱스와 홍삼을 발효하여 저분자 진세노사이드인 compound K (CK)로 생물전환되는지를 확인하였다. 프로바이오틱스 19종의 유전체 분석결과, 진세노사이드 Rb1에서 CK로 전환에 관련된 β-glucosidase는 19종 모든 균주에서 확인되었고, α-arabinofuranosidase 유전자는 3종의 균주, β-xylosidase는 6종 균주, α-rhamnosidase는 8종의 균주에서 확인되었다. 이 중 B. longum CBT BG7는 Rb1으로부터 CK까지 전환시켜, CK 함량을 증가시켰다. 또한, B. breve CBT BR3와 B. lactis CBT BL3은 Rb1을 Rd로 전환시켰다. 균체를 파쇄 또는 미파쇄하여 진세노사이드 전환 반응을 비교했을 때 미파쇄물이 F2와 CK로의 높은 전환량과 수율을 보였다. CBT BG7 + BL3와 BG7 + BR3 혼합균주는 CBT BG7 단독보다 진세노사이드 F2의 함량을 증가시켰다. CBT BG7과 α-amylase 효소를 함께 반응하였을 때에 F2 함량이 증가되었다. 본 연구는 한국형 프로바이오틱스인 CBT BG7, BR3, BL3와 홍삼을 함께 섭취할 경우, 건강에 도움을 주는 생리활성물질인 CK의 생산을 확인하였다. 추후 부탄올 등 다양한 추출용매를 활용하여 생물전환 효율 및 CK로의 전환율에 대한 추가 연구가 필요해 보인다.

• 한국식품과학회지
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• 제14권3호
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• pp.197-202
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• 1982

인삼제품제조용(人蔘製品製造用)엑기스의 숙성중(熟成中)에 일어나는 ginsenosides의 분해(分解)에 미치는 온도(溫度)의 영향(影響)을 구명(究明)하기 위하여 숙성온도(熟成溫度) 및 시간(時間)에 따른 ginsenosides의 함량변화(含量變化)로써 분해속도상수(分解速度常數) 및 반감기(牛減期)를 구(求)하였고 분해속도상수(分解速度常數)와 온도(溫度)에 대(對)한 Arrhenius plot에 의하여 활성화(活性化)에너지 및 $Q_{10}$ value를 구(求)하여 ginsenosides의 분해속도상수(分解速度常數)의 온도의존성(溫度依存性)에 대(對)한 관계식(關係式)을 설정(設定)하였다. 가. ginsenosides의 분해반응(分解反應)은 1차반응(次反應)을 나타냈으며 분해시(分解時)의 반감기(半減期)가 $100^{\circ}C$에서 34시간(時間), $90^{\circ}C$에서 70시간(時間), $80^{\circ}C$에서는 131시간(時間)이므로 ginsenosides의 함량변화(含量變化)만을 고려(考慮)한다면 $80^{\circ}C$이하(以下)의$70^{\circ}C$ 부근에서 숙성(熟成)함이 바람직하다. 나. 숙성중(熟成中)에 ginsenoside-Re가 감소(減少)하는 대신 $ginsenoside-Rg_2$가 증가(增加)하고 $ginsenoside-Rg_1$이 감소(減少)하는 대신 $ginsenoside-Rh_1$이 증가(增加)하므로 ginsenosides의 상호변환관계(相互變換關係)가 인정(認定)되었다. 다. ginsenosides의 분해시(分解時)의 온도상화(速度常數)가 $80^{\circ}C$에서 $5.30{\times}10^{-3}\;hr^{-1}$, $90^{\circ}C$에서 $9.90{\times}10^{-3}\;hr^{-1}$, 100"C에서는 $20.50{\times}10^{-3}\;hr^{-1}$으로서 숙성온도(熟成溫度)가 $10^{\circ}C$높아질 때마다 분해속도상수(分解速度常數)가 약(約) 2배(培) 증가(增加)하였고 또 $Q_{10}$ value도 $2.01{\sim}3.49$로서 숙성온도(熟成溫度)가 높아질수록 ginsenosides는 상대적(相對的)으로 불안정(不安定)하였다. 라. ginsenosides분해시(分解時)의 활성화(活性化)에너지 ($E_a$)는 $16.8{\sim}30.1$ kcal/mole의 범위 안에 있으며 ginsenoside-Re 및 $-Rg_1$이 $ginsenoside-Rb_1,\;-Rb_2$, -Rc 및 -Rd 보다 훨씬 높으므로 troil saponin이 diol saponin보다 온도(溫度)의 영향(影響)을 더 많이 받고 있었다. 마. total ginsenosides의 분해반응시(分解反應時)의 활성화(活性化)에너지($E_a$)는 17.7kcal/mole이었고 분해속도상수(分解速度常數)의 온도의존성(溫度依存性)은 $k=4.574{\times}10^8{\exp}(-8898.8/T)$의 관계식(關係式)으로 표시(表示)할 수 있다

• Food Science and Biotechnology
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• 제16권4호
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• pp.636-640
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• 2007

In order to investigate the major metabolite patterns of aged Panax ginseng C.A. Meyer roots, the ginsenoside contents for white ginseng roots of various ages were compared. The 1-year to 6-year old roots were extracted with methanol, and then the methanol-soluble metabolites were analyzed by high performance liquid chromatography (HPLC). The metabolite contents of the 1-year and 2-year roots, including the ginsenosides and minor components, were not different, but the $Rg_1$, Re, and Rc ginsenoside contents between the 2-year and 3-year roots showed significant differences. $Rg_1$ and Rc increased significantly in the 1-year to 2-year roots, and Re increased significantly from the 3-year root age. Rd increased slightly until the 2-year age and decreased from the 3-year age. Based on the ginsenoside distributions and contents at various root ages, we have suggested 2 biogenesis schemes using the ginsenosides that have been isolated from the roots of P. ginseng so far.

• 생명과학회지
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• 제26권2호
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• pp.247-252
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• 2016

산양삼은 식품 또는 약초로써 많이 사용되고 있다. 이번 연구의 목표는 high performance liquid chromatography (HPLC) - charged aerosol detection (CAD)에 의해 산양삼의 추출물에 사포닌들의 분석을 최적화 하는 것이다. CAD는 물리적인 특성은 물론이고 입자크기, 스펙트럼 특성과는 무관하게 비휘발성 물질도 분석할 수 있다. 산양삼 추출물 중 Gensenoside Rb1, Rd, Rg1, Rf, Re 및 Rh1을 분석하였다. HPLC-CAD분석을 위한 사포닌 추출물은 건조 산양삼 10 g에 95% 에탄올 100 ml을 넣어 80℃에서 24시간 동안 추출하여 사포닌을 얻었다. 6개의 주요한 사포닌을 정량화하였을 경우 값은 다음과 같다. 사포닌들의 함량은 Rb1 (5.48±0.12 mg/g), Rd (5.33±0.14 mg/g), Rg1 (12.80±0.05 mg/g), Rf (19.08±0.68 mg/g), Re (19.87± 0.05 mg/g), 및 Rh1 (16.47±0.16 mg/g)로 확인하였다. 대체적으로 산양삼 추출물의 사포닌은 protopanaxatriol (Rg1, Rf, Re, Rh1)의 값이 protopanaxadiol (Rb1, Rd)보다 높게 확인 되었다. 이번 연구에서는 산양삼 사포닌의 분석조건을 HPLC-CAD를 이용하여 최적화하였고 제품화를 위해 약리활성에 관한 연구도 매우 중요할 것이다.

• Journal of Ginseng Research
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• 제47권2호
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• pp.255-264
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• 2023

Background: Red ginseng (RG) alleviates psychiatric disorders. Fermented red ginseng (fRG) alleviates stress-induced gut inflammation. Gut dysbiosis causes psychiatric disorders with gut inflammation. To understand the gut microbiota-mediated action mechanism of RG and fRG against anxiety/depression (AD), we investigated the effects of RG, fRG, ginsenoside Rd, and 20(S)-β-D-glucopyranosyl protopanaxadiol (CK) on gut microbiota dysbiosis-induced AD and colitis in mice. Methods: Mice with AD and colitis were prepared by exposing to immobilization stress (IS) or transplanting the feces of patients with ulcerative colitis and depression (UCDF). AD-like behaviors were measured in the elevated plus maze, light/dark transition, forced swimming, and tail suspension tests. Results: Oral gavage of UCDF increased AD-like behaviors and induced neuroinflammation, gastrointestinal inflammation, and gut microbiota fluctuation in mice. Oral administration of fRG or RG treatment reduced UCDF-induced AD-like behaviors, hippocampal and hypothalamic IL-6 expression, and blood corticosterone level, whereas UCDF-suppressed hippocampal BDNF⁺NeuN⁺ cell population and dopamine and hypothalamic serotonin levels increased. Furthermore, their treatments suppressed UCDF-induced colonic inflammation and partially restored UCDF-induced gut microbiota fluctuation. Oral administration of fRG, RG, Rd, or CK also decreased IS-induced AD-like behaviors, blood IL-6 and corticosterone and colonic IL-6 and TNF-α levels, and gut dysbiosis, while IS-suppressed hypothalamic dopamine and serotonin levels increased. Conclusion: Oral gavage of UCDF caused AD, neuroinflammation, and gastrointestinal inflammation in mice. fRG mitigated AD and colitis in UCDF-exposed mice by the regulation of the microbiota-gut-brain axis and IS-exposed mice by the regulation of the hypothalamic-pituitary-adrenal axis.