[6]-Gingerol이 인체 유방암세포 MDA-MB-231에서 Bcl-2와 Bax 발현에 미치는 영향

서은영(Eun-Young Seo),김우경(Woo-Kyung Kim) 한국식품영양과학회 2006 한국식품영양과학회지 Vol.35 No.6

본 연구는 생강의 대표적인 비휘발성 매운맛 성분인 [6]-gingerol이 인체 유방암세포 MDA-MB-231에서 세포사멸에 미치는 영향을 살펴보았으며 그 결과는 다음과 같다. 세포사멸을 억제하는 단백질인 Bcl-2의 발현은 [6]-gingerol의 농도가 증가할수록 발현이 감소되었으며, mRNA 수준에서도 같은 양상을 보였다. 세포사멸을 유도하는 Bax의 단백질 발현은 [6]-gingerol의 농도가 증가되어도 유의적인 차이는 나타나지 않았으며 mRNA 수준에도 별 영향을 미치지 않았다. 그러나 세포사멸의 지표로 사용되는 Bcl-2/Bax의 비율은 [6]-gingerol의 농도가 증가할수록 감소를 보였다. 그리고 [6]-gingerol의 농도가 증가할수록 caspase-3의 활성이 증가하였다. 이상의 결과들로 볼 때, 인체 유방암 세포인 MDA-MB-231에서 [6]-gingerol은 암세포의 증식을 억제하고, 세포사멸을 유도하는 효과가 있는 것으로 사료된다. We investigated the effect of gingerol (Zingiber officinale Roscoe, Zingiberaceae) on Bcl-2 and Bax expression in MDA-MB-231 human breast cell lines. The oleoresin from rhizomes of ginger contains [6]- gingerol (1-[4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone). We previously reported that [6]- gingerol inhibits cell proliferation in MDA-MB-231 human breast cancer cell lines. In this study, we examined protein and mRNA expression associated with cell apoptosis in MDA-MB-231 human breast cancer cell lines. We cultured MDA-MB-231 cells in presence of various concentrations 0, 2.5, 5 and 10 μM of [6]-gingerol. Bcl-2 protein and its mRNA levels were decreased dose-dependently in cells treated with [6]-gingerol, but Bax protein and its mRNA levels were unchanged by [6]-gingerol treatment. Bcl-2/Bax ratio was decreased in a dose dependent manner treated with [6]-gingerol. Caspase-3 activity was significantly increased dose-dependently in cell treated with [6]-gingerol (p<0.05). In conclusion, we have shown that [6]-gingerol induces apoptosis in MDA-MB-231 human breast cancer cell lines.

Apoptotic Effects of 6-Gingerol in LNCaP Human Prostate Cancer Cells

김현우,오덕희,정채용,권동득,임영채 순천향대학교 순천향의학연구소 2011 Journal of Soonchunhyang Medical Science Vol.17 No.2

Objective: 6-Gingerol, one component of ginger (Zingiber officinale) compound, has been known to possess anti-inflammatory, analgesic,anti-emetic, and anti-cancer effects. In this study, the apoptotic ability of 6-gingerol was investigated in human prostate cancer cells. Methods: 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide (MTT) assay, flow cytometry, and western blot analysis were done in LNCaP human prostate cancer cell lines treated with the various doses of 6-gingerol for the different durations of drug exposure. Results: 6-Gingerol in doses ranging from 100 to 300 μM induced dose- and time-dependent inhibition of cell viability in prostate cancer cells by using MTT assay. Maximal inhibition of cell viability was observed at 300 μM of 6-gingerol for 48 hours treatment in LNCaP cells. 6-Gingerol at the dose of 100 μM did not produce any significant change in apoptotic cells in flow cytometry analysis. However, significant increase in sub-G0/G1 phase was observed in cells treated with 200 and 300 μM of 6-gingerol. Any significant cell cycle arrest was not induced by 6-gingerol. In western blotting analysis, expression of caspase-3 was not evident in cells treated with 6-gingerol for 24 hours. However, 48 hours treatment with 6-gingerol altered the expression of caspase-3 in LNCaP cells. Expression of cleaved poly showed the dose-dependent fashion in both 24 hours and 48 hours treatment of 6-gingerol. Conclusion: These observations suggest that 6-gingerol may induce apoptosis in LNCaP human prostate cancer cells.

Apoptotic Effects of 6-Gingerol in LNCaP Human Prostate Cancer Cells

Hyun-Woo Kim,Deuk-Hee Oh,Chaeyong Jung,Dong-Deuk Kwon,Young-Chai Lim 순천향대학교 순천향의학연구소 2011 Journal of Soonchunhyang Medical Science Vol.17 No.2

Objective: 6-Gingerol, one component of ginger (Zingiber officinale) compound, has been known to possess anti-inflammatory, analgesic, anti-emetic, and anti-cancer effects. In this study, the apoptotic ability of 6-gingerol was investigated in human prostate cancer cells. Methods: 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide (MTT) assay, flow cytometry, and western blot analysis were done in LNCaP human prostate cancer cell lines treated with the various doses of 6-gingerol for the different durations of drug exposure. Results: 6-Gingerol in doses ranging from 100 to 300 μM induced dose- and time-dependent inhibition of cell viability in prostate cancer cells by using MTT assay. Maximal inhibition of cell viability was observed at 300 μM of 6-gingerol for 48 hours treatment in LNCaP cells. 6-Gingerol at the dose of 100 μM did not produce any significant change in apoptotic cells in flow cytometry analysis. However, significant increase in sub-G0/G1 phase was observed in cells treated with 200 and 300 μM of 6-gingerol. Any significant cell cycle arrest was not induced by 6-gingerol. In western blotting analysis, expression of caspase-3 was not evident in cells treated with 6-gingerol for 24 hours. However, 48 hours treatment with 6-gingerol altered the expression of caspase-3 in LNCaP cells. Expression of cleaved poly showed the dose-dependent fashion in both 24 hours and 48 hours treatment of 6-gingerol. Conclusion: These observations suggest that 6-gingerol may induce apoptosis in LNCaP human prostate cancer cells.

아임계수 추출에서 6-gingerol의 6-shogaol 전환을 위한 생강 건조 조건 최적화

고민정,남화현,정명수 한국식품과학회 2019 한국식품과학회지 Vol.51 No.5

6-gingerol can be converted to 6-shogaol, one of the predominant active compounds found in ginger, via processing such as drying and extraction. Subcritical water extraction is the environmentally friendly method of extraction of bioactive compounds using only purified water as a solvent. This study investigated subcritical water extraction (190oC, 15 min) of 6-gingerol, and 6-shogaol from dried ginger (Zingiber officinale) including drying conditions such as temperature (room temperature, 60, 80oC, and freeze drying) and time duration for drying (1-4 h). The amount of 6- gingerol was found to be reduced, and that of 6-shogaol was found to be increased depending upon the water content of dried ginger. Upon oven-drying ginger at 60oC for 2 h, the maximum yields of 6-gingerol (0.18±0.02 mg/g fresh weight), and 6-shogaol (0.47±0.02 mg/g fresh weight) were obtained upon subcritical water extraction.

Inhibitory Effects of 6-Gingerol on Cytochrome P450 in Human Liver Microsomes

주수연,임영채 대한임상약리학회 2011 Translational and Clinical Pharmacology Vol.19 No.1

a 배경: 일상 식이 생활에서 흔히 쓰이는 생강(ginger)의 한 성분인 6-gingerol은 질병 치료 과정 중에 사용하는 약물과 상호 작용을 일으킬 수 있다. 그러나 인체 간 대사 효소인 시토크롬 P450 활성도에 대한 6- gingerol의 효과는 아직 알려져 있지 않다. 본 연구에서는 인체 간 미세소체에서 6-gingerol이 시토크롬 P450대사 효소에 미치는 억제 효과를 연구하고자 하였다. 방법: 인체 간 미세소체 모델을 이용하여 다양한 농도의 6-gingerol과 각각의 CYP450에 특이적인 기질을 함께 배양하였으며, 각각의 대사물을 HPLC로 측정하였다. 본 연구에서 사용된 CYP효소에 의해 촉매 되는 반응에는 CYP1A2에 의한 phenacetin O-deethylation, CYP2C9에 의한 tolbutamide 4-hydroxyltion, CYP2C 19에 의한 S-mephenytoin 4’-hydroxylation, CYP2D6에 의한 dextromethorphan O-demethylation, CYP2E1에 의한 chlorzoxazone 6-hydroxylation, 그리고 CYP3A4에 의한 midazolam 1-hydroxylation이었다. 결과: 6-gingerol은 IC_50가 100 μM을 상회할 정도로 CYP2C9, CYP2D6, CYP2E1 그리고 CYP3A4의 활성도에 큰 영향을 미치지 않았다. 그러나 6-gingerol은 CYP 2C19과 CYP 1A2에 대하여 Ki 수치가 각각 13 μM과 29 μM이 될 정도로 강한 억제 효과를 나타내었다. CYP1A2에 대하여 6-gingerol은 상경적인 형태의 억제를 초래하였다. 결론: 이러한 결과는 6-gingerol이 CYP1A2과 CYP2C19의 활성도를 잠재적으로 억제할 수 있음을 시사하였다.

Conversion of 6-gingerol to 6-shogaol in ginger (<i>Zingiber officinale</i>) pulp and peel during subcritical water extraction

Ko, Min-Jung,Nam, Hwa-Hyun,Chung, Myong-Soo Elsevier 2019 Food chemistry Vol.270 No.-

<P><B>Abstract</B></P> <P>Subcritical water extraction is an eco-friendly method for the extraction of less polar compounds without the use of organic solvents. This study determined the extraction conditions that maximize the contents of 6-gingerol and 6-shogaol obtained from ginger pulp and peel. The highest yields of 6-gingerol (0.68 ± 0.08 mg/g), and 6-shogaol (0.39 ± 0.03 mg/g) were obtained from ginger pulp at the extraction conditions of 130 °C/25 min, and 190 °C/15 min. 6-Shogaol content increased with the increasing extraction temperature and extraction time due to the conversion of 6-gingerol to 6-shogaol by thermal cracking. The antioxidant activity of ginger extracts were increased depending on the increasing of 6-shogaol content.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Extraction of 6-gingerol and 6-shogaol from ginger was conducted by using subcritical water. </LI> <LI> The contents of 6-gingerol and 6-shogaol from the peel were smaller than pulp. </LI> <LI> 6-Gingerol can be converted to 6-shogaol via processes of subcritical water extraction. </LI> <LI> The antioxidant activity was increased depending on the 6-shogaol content. </LI> </UL> </P>

가압조건에서 생강 유래 6-shogaol 변환을 위한 가열 조건 최적화

박호영(Ho-Young Park),하상근(Sang Keun Ha),최지원(Jiwon Choi),최희돈(Hee-don Choi),김윤숙(Yoonsook Kim),박용곤(Yongkon Park) 한국식품과학회 2014 한국식품과학회지 Vol.46 No.5

본 연구는 다진 생강에 다량 함유된 6-gingerol을 뇌질환 개선등의 기능성이 보고된 6-shogaol로 변환시키기 위하여 CO₂를 이용한 6.4㎫의 가압조건에서 가열 온도와 시간을 변수로 두고 중심합성설계법을 이용한 최적반응표면분석법을 적용하였다. 적용 온도 70-130℃ (X₁)와 적용 시간 95-265분(X₂)을 독립변수로, 6-gingerol함량(Y₁, ㎎/g dried ginger)와 6-shogaol함량(Y₂, ㎎/g dried ginger)을 종속변수로 설정하였다. 그 결과 온도와 시간이 대체적으로 증가할수록 6-gingerol은 감소하였으며 반대로 6-shogaol은 증가하였다. 도출된 반응표면 설계를 분석한 결과 압력이 6.4 ㎫일 경우 적용 온도(X₁)는 130oC, 적용 시간(X₂)는 204분이었다. 최적반응표면분석 결과 예측된 6-gingerol과 6-shogaol 함량은 각각 건조시킨 생강을 기준으로 0.13, 3.85 ㎎/g이며, 이때 만족도는 0.991이었다. 본 실험 결과를 통하여 도출된 가압조건에서의 열처리 방법은 스팀 등을 이용한 물리적 열처리 기술에 비해 소요 시간과 소모되는 에너지를 줄일 수 있었고, 6-gingerol에서 6-shogaol로의 변환율이 탁월하기 때문에 친환경적이고 효율적인 6-shogaol을 얻을 수 있는 기술임을 확인할 수 있었다. Under optimized condition mild pressure in combination with specific temperature for heat treatment transform the 6-gingerol into 6-shogaol. The purpose of this study was to optimize the conditions used for heat treatment under pressure for increasing 6-shogaol content in ginger (Zingiber officinale Roscoe). A central composite experimental design was used to evaluate the effects of application temperature (70-130℃) and temperature-holding time (95-265 min) on the transformation of 6-shogaol. The experimental values were shown to be in significantly good agreement with the predicted values (adjusted determination coefficient, R²<SUB>Adj</SUB>=0.9857). 6-Shogaol content increased as the application temperature and temperature-holding time increased. By analyzing the response surface plots, the optimum conditions of heat treatment (temperature and time) for increasing 6-shogaol content were found to be 127℃ and 109 min, respectively. Under these optimal conditions, the predicted 6-shogaol content was 3.98 ㎎/g dried ginger. The adequacy of the model equation for predicting the optimum response values was effectively verified by the validation data.

Control of membrane biofouling by 6-gingerol analogs: Quorum sensing inhibition

Ham, So-Young,Kim, Han-Shin,Jang, Yongsun,Sun, Peng-Fei,Park, Jeong-Hoon,Lee, John Seungwu,Byun, Youngjoo,Park, Hee-Deung Elsevier 2019 Fuel Vol.250 No.-

<P><B>Abstract</B></P> <P>Biofouling is a major problem in operating reverse osmosis (RO) processes. Although biocides such as chlorine are commonly used to reduce biofouling, their strong oxidative activity and toxicity negatively affect the operation of RO processes. 6-gingerol analogs, structural derivatives of the main component of ginger, are quorum sensing (QS) inhibitors. In this study, 6-gingerol analogs were applied to reduce biofouling in RO processes. The 6-gingerol analogs could inhibit <I>Pseudomonas aeruginosa</I> biofilm formation at low concentrations via QS disrupting activities without affecting the growth of the species. Notably, 6-gingerol analogs increased the permeate flux 36–52% in the operation of a model RO unit, with no damage to the membrane surface physically and chemically. Therefore, the results of this study clearly demonstrated that 6-gingerol analogs are effective biofilm inhibitors that could be used to mitigate biofouling in RO processes.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 6-Gingerol analogs reduced biofilm formation without bacterial growth inhibition. </LI> <LI> 6-Gingerol analogs did not affect morphology and chemical structure of RO membranes. </LI> <LI> Permeate flux was increased by treatment of 6-gingerol analogs. </LI> <LI> 6-Gingerol analogs could control biofouling by regulating the expression of QS related genes. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Optimization of Extraction Conditions for the 6-Shogaol-rich Extract from Ginger (Zingiber officinale Roscoe)

Ok, Seon,Jeong, Woo-Sik The Korean Society of Food Science and Nutrition 2012 Preventive Nutrition and Food Science Vol.17 No.2

6-Shogaol, a dehydrated form of 6-gingerol, is a minor component in ginger (Zingiber officinale Roscoe) and has recently been reported to have more potent bioactivity than 6-gingerol. Based on the thermal instability of gingerols (their dehydration to corresponding shogaols at high temperature), we aimed to develop an optimal process to maximize the 6-shogaol content during ginger extraction by modulating temperature and pH. Fresh gingers were dried under various conditions: freeze-, room temperature (RT)- or convection oven-drying at 60 or $80^{\circ}C$, and extracted by 95% ethanol at RT, 60 or $80^{\circ}C$. The content of 6-shogaol was augmented by increasing both drying and extraction temperatures. The highest production of 6-shogaol was achieved at $80^{\circ}C$ extraction after drying at the same temperature and the content of 6-shogaol was about 7-fold compared to the lowest producing process by freezing and extraction at RT. Adjustment of pH (pH 1, 4, 7 and 10) for the 6-shogaol-richest extract (dried and extracted both at $80^{\circ}C$) also affected the chemical composition of ginger and the yield of 6-shogaol was maximized at the most acidic condition of pH 1. Taken together, the current study shows for the first time that a maximized production of 6-shogaol can be achieved during practical drying and extraction process of ginger by increasing both drying and extracting temperatures. Adjustment of pH to extraction solvent with strong acid also helps increase the production of 6-shogaol. Our data could be usefully employed in the fields of food processing as well as nutraceutical industry.

Optimization of Extraction Conditions for the 6-Shogaol-rich Extract from Ginger (Zingiber officinale Roscoe)

Seon Ok,Woo-Sik Jeong 한국식품영양과학회 2012 Preventive Nutrition and Food Science Vol.17 No.2

6-Shogaol, a dehydrated form of 6-gingerol, is a minor component in ginger (Zingiber officinale Roscoe) and has recently been reported to have more potent bioactivity than 6-gingerol. Based on the thermal instability of gingerols (their dehydration to corresponding shogaols at high temperature), we aimed to develop an optimal process to maximize the 6-shogaol content during ginger extraction by modulating temperature and pH. Fresh gingers were dried under various conditions: freeze-, room temperature (RT)- or convection oven-drying at 60 or 80oC, and extracted by 95% ethanol at RT, 60 or 80oC. The content of 6-shogaol was augmented by increasing both drying and extraction temperatures. The highest production of 6-shogaol was achieved at 80oC extraction after drying at the same temperature and the content of 6-shogaol was about 7-fold compared to the lowest producing process by freezing and extraction at RT. Adjustment of pH (pH 1, 4, 7 and 10) for the 6-shogaol-richest extract (dried and extracted both at 80oC) also affected the chemical composition of ginger and the yield of 6-shogaol was maximized at the most acidic condition of pH 1. Taken together, the current study shows for the first time that a maximized production of 6-shogaol can be achieved during practical drying and extraction process of ginger by increasing both drying and extracting temperatures. Adjustment of pH to extraction solvent with strong acid also helps increase the production of 6-shogaol. Our data could be usefully employed in the fields of food processing as well as nutraceutical industry.