꽈리 추출물 투여가 마우스 간 Glutathione S-transferase 활성에 미치는 영향

Lee, Sang-il 啓明專門大學 産業開發硏究所 1999 啓明硏究論叢 Vol.17 No.2

천연물로부터 생리활성 물질을 검색하는 일환으로 우리나라에 널리 분포하는 꽈리를 대상으로 하여 여러단계를 거쳐 n-butanol 추출물을 얻고 실험동물에 용량별 및 기간별로 투여하면서 간조직 glutathione S-transferase의 활성 및 glutathione의 함량에 미치는 영향을 검토하여 다음과 같은 성적을 얻었다. 꽈리 n-butanol 추출물을 4일간 체중 kg당 100, 200 및 400mg씩 복강내로 투여하였을 때, 체중당 간무게 및 혈청 alanine aminotransferase의 활성은 유의한 변동이 없었고 과산화지질의 함량은 투여량에 반비례하여 감소하였다. 한편 간조직 glutathione S-transferase의 환성은 꽈리 추출물 투여량과 투여기간에 반비례하여 억제되었으며, glutathione의 함량 변동도 이와 유사하였다. 한편 동력학적인 측면에서 glutathione S-transferase의 활성 변동을 관찰하였을 때, 꽈리 n-butanol 추출물을 투여한 실험군이 생리식염수를 주사한 대조군에 비해 Vmax치가 현저히 감소하였다. To evaluate the effect of ground cherry n-butanol extract on the hepatic glutathione S-transferse, 100, 200 or 400mg/kg of ground cherry n-butanol extract were daily given to mice. The ratio of liver weight per body weight and serum alanine aminotransferase activity were not significantly changed, whereas hepatic lipid peroxide content was decreased as dose dependent manner. And ground cherry n-butanol extract treatment to the mice led to decreased activity of glutathione S-transferase activity and decreased content of reduced glutathione compared with the only physiological saline treated mice. The glutathione S-transferase activity was decreased as time-dependent manner by the injection of ground cherry n-butanol extract (200mg/kg) for one, two or four days. And the Vmax value without affecting the Km value for 1-chloro-2,4-dinitrobenzene was decreased by the ground cherry n-butanol extract treatment. From the above result, it is concluded that the ground cherry n-butanol extract may decrease the hepatic glutathione S-transferase activity due to an alteration in the quantity of enzyme protein, but further research in this field is needed.

흰쥐 담즙울체간의 Glutathione S-Transferase, Glutathione Reductase 및 Glutathione Peroxidase의 활성도

권용철,곽춘식,문교철 啓明大學校 醫科大學 1990 계명의대학술지 Vol.9 No.2

Changes in the activities of the following enzymes have been studied over a period of forty two days after the ligation of common bile duct in rats: cytosolic, mitochondrial and microsomal glutathione S-transferase, cytosolic glutathione reductase and cytosolic glutathione peroxidase of cholestatic liver. The activity of cytosolic glutathione S-transferase in the cholestatic rat liver strikingly diminished between the third and the forty-second days after the ligation of common bile duct and of mitochondrial glutathione S-transferase also showed significant decrease between the fourteenth and the forty-second days after operation. However, the microsomal glutathione S-transferase activity in the cholestatic rat liver showed a substantial increase between the seventh and twenty-eight days after operation. The cytosolic glutathione reductase activity in the cholstatic rat liver elevated considerably between the second and the forty-second days after operation, but the cytosolic glutathione peroxidase activity in the cholestatic rat liver had a significant diminution between the fourteenth and the forty-second days after the ligation of common bile duct.

Relationship between the Glutathione-S-Transferase P1, M1, and T1 Genotypes and Prostate Cancer Risk in Korean Subjects

권동득,이재환,한동엽,서일영,박승철,정희종,양윤식,채수천,나경숙,모금자,김정중,임정식 대한비뇨의학회 2011 Investigative and Clinical Urology Vol.52 No.4

Purpose: The glutathione-S-transferase (GST)P1, GSTM1, and GSTT1 genotypes have been associated with an increased risk of prostate, bladder, and lung cancers. The aim of this study was to investigate the association between the GSTP1, GSTM1, and GSTT1 genotypes and the risk of prostate cancer in Korean men. Materials and Methods: The study group consisted of 166 patients with histologically confirmed prostate cancer. The control group consisted of 327 healthy, cancer-free individuals. The diagnosis of prostate cancer was made by transrectal ultrasound-guided biopsy. Patients with prostatic adenocarcinoma were divided into organ-confined (≤pT2) and non-organ-confined (≥pT3) subgroups. The histological grades were subdivided according to the Gleason score. The GSTP1, GSTM1, and GSTT1 genotypes were determined by using polymerase chain reaction-based methods. The relationship among GSTP1, GSTM1, and GSTT1 polymorphisms and prostate cancer in a case-control study was investigated. Results: The frequency of the GSTM1 null genotype in the prostate cancer group (54.2%) was higher than in the control group (odds ratio=1.53, 95% confidence interval=1.20- 1.96). The comparison of the GSTP1, GSTM1, and GSTT1 genotypes and cancer prognostic factors, such as staging and grading, showed no statistical significance. Conclusions: An increased risk for prostate cancer may be associated with the GSTM1 null genotype in Korean men, but no association was found with the GSTT1 or GSTP1 genotypes.

추출농도에 따른 오미자 및 구기자를 첨가한 한방약술의 품질특성

오성천 한국응용과학기술학회 2019 한국응용과학기술학회지 Vol.36 No.1

In this study, the following is the result of measuring the quality characteristics of herbal wine and the active inhibition of Glutathione S-transferase in order to measure the release of physiological active substances according to the concentration of extracts. The pH level of herbal wine was 4.4, up from 3.9 before fermentation. These changes are attributed to fermentation and organic acids during alcoholic fermentation. The acidity of herbal wine was 0.55%, about six times higher than the pre-fermentation control of 0.09%. These results show that organic acids are used for flavor formation, ether, in combination with alcohol. The inhibitory activity of glutathione S-transferase were 5.1±0.31 in herbal wine 15%, 6.5±0.6 in herbal wine 20%, 7.6±0.6 in herbal wine 25%, 8.4±0.2 in herbal wine 30% and 9.7±0.7 in herbal wine 35%. As the extract concentration was increased the inhibitory activity of glutathione S-transferase were significantly increased (<0.05). 본 연구에서는 한약재의 활용도를 높이기 위한 연구로 추출물 농도에 따른 생리활성물질의 용출량을 측정하기 위해 한방약술의 품질 특성과 Glutathione S-transferase의 활성 저해능을 측정한 결과는 다음과 같다. 한방약술의 pH결과는 4.4로 발효 전의 대조구 3.9보다 증가하였다. 이러한 변화는 알코올 발효과정 중 발효부산물 및 유기산 때문으로 사료된다. 한방약술의 산도는 0.55%로 발효 전의 대조구 0.09%보다 약 6배 증가하였다. 이런 결과는 유기산이 알코올 등과 결합하여 ester와 같은 향미 형성 등에 이용되는 것을 알 수 있다. 한방약술 15%의 glutathione S-transferase의  활성 저해능 5.1±0.3, 한방약술 20%는 저해능 6.5±0.5, 한방약술 25%는 7.6±0.6, 한방약술 30%는 8.4±0.2, 최대 농도인 35%에서의 저해능은 9.7±0.7로 나타내었다. 추출 농도별로 glutathione S-transferase의 활성 저 해능은  통계학적으로  유의한 차이가 있음을 보였다 (p<0.05).

추출용매에 따른 진피 추출물의 항산화 활성

이성구,오성천,장재선,Lee, Sung-Gu,Oh, Sung-Cheon,Jang, Jae-Seon 한국식품영양학회 2015 韓國食品營養學會誌 Vol.28 No.3

본 연구에서는 진피의 활용도를 높이기 위한 연구의 일환으로 유기용매별에 따른 생리활성물질의 용출량을 측정하기 위해, 진피와 에탄올 진피 추출물을 대상으로 유기용매인 에틸 아세테이트, 아세톤, 염화 메틸렌, 메탄올을 이용하여 추출한 시료를 대상으로 총 폴리페놀 함량, 전자공여능, glutathione S-transferase(GST)의 활성 저해력을 측정한 결과는 다음과 같다. 1. 총 폴리페놀 함량은 ethyl acetate인 경우 진피는 $928.48{\pm}1.19{\mu}g\;GAE/mL$, 에탄올 추출 진피는 $664.64{\pm}0.74{\mu}g\;GAE/mL$로, acetone인 경우 진피는 $886.03{\pm}0.44{\mu}g\;GAE/mL$, 에탄올 추출 진피는 $702.67{\pm}0.85{\mu}g\;GAE/mL$로, methylene chloride인 경우 진피는 $413.08{\pm}1.39{\mu}g\;GAE/mL$, 에탄올 추출 진피는 $429.64{\pm}0.61{\mu}g\;GAE/mL$로, methanol인 경우 진피는 $12,648.60{\pm}0.56{\mu}g\;GAE/mL$, 에탄올 추출 진피는 $16,108.20{\pm}0.73{\mu}g\;GAE/mL$로 나타나, 진피나 에탄올 추출 진피는 모두 methanol로 추출한 것이 상대적으로 높게 나타났으며, 총 폴리페놀의 함량 차이는 유기용매별 통계적으로 유의한 차이가 나타났다(p<0.05). 2. 전자공여능은 ethyl acetate인 경우 진피는 62.80%, 에탄올 추출 진피는 51.49%로 나타났으며, acetone인 경우 진피는 97.43%, 에탄올 추출 진피는 63.17%로 나타났으며, methylene chloride인 경우 진피는 52.20%, 에탄올 추출 진피는 67.68%로 나타났으며, methanol인 경우 진피는 97.63%, 에탄올 추출 진피는 96.18%로 나타났다. Electron donating ability(EDA)는 유기용매 중 메탄올로 추출하였을 때가 상대적으로 가장 높게 나타났으며, 유기용매별로 통계적으로 유의한 차이가 나타났다(p<0.05). 3. Glutathione S-transferase(GST)에 대한 활성 저해능은 ethyl acetate인 경우 진피는 76.22%, 에탄올 추출 진피는 75.54%로 나타났으며, methylene chloride인 경우 진피는 31.73%, 에탄올 추출 진피는 73.53%로 나타났으며, methanol인 경우 진피는 97.48%, 에탄올 추출 진피는 48.70%로 나타났다. Glutathione S-transferase(GST)에 대한 활성 저해능은 진피인 경우 유기용매 중 메탄올로 추출하였을 때가 가장 높게 나타났고, 에탄올 추출 진피인 경우는 에탄올과 methylene chloride로 추출할 때가 높게 나타났으며, 유기용매별로 통계적으로 유의한 것으로 나타났다(p<0.05). In this study, the total polyphenol content, electron donating ability (EDA) and inhibitory activity of glutathione S-transferase (GST) of freeze-dried Citrus unshiu extracts were examined. The Citrus unshiu extracts was obtained from four solvents such as ethyl acetate, acetone, methyl chloride and methanol, to evaluate its functional properties. Total polyphenol contents were measured in the two different extracts, and the extracts were screened for their potential antioxidant activities using tests such as electron donating ability (EDA), glutathione S-transferase (GST). The total polyphenol contents of Citrus unshiu extracts were $928.48{\pm}1.19{\mu}g\;GAE/mL$ in ethyl acetate (EA), $886.03{\pm}0.44{\mu}g\;RE/mL$ in acetone (AC), $413.08{\pm}1.39{\mu}g\;GAE/mL$ in methylene chloride (MC), $12,648.60{\pm}0.56{\mu}g\;GAE/mL$ in methanol (MeOH), respectively. Also, the total polyphenol contents of EtOH Citrus unshiu extracts were $664.64{\pm}0.74{\mu}g\;GAE/mL$ in EA, $702.67{\pm}0.85{\mu}g\;RE/mL$ in AC, $429.64{\pm}0.61{\mu}g\;GAE/mL$ in MC, $16,108{\pm}0.73{\mu}g\;GAE/mL$ in MeOH, respectively. The total polyphenol contents were significantly difference (p<0.05) between the solvents. The electron donating ability of Citrus unshiu extracts were $62.80{\pm}0.36%$ in EA, $97.43{\pm}0.51%$ in AC, $52.20{\pm}0.30%$ in MC, $97.63{\pm}0.46%$ in MeOH, respectively. Also, the electron donating ability of EtOH Citrus unshiu extracts were $51.49{\pm}0.26%$ in EA, $63.17{\pm}0.31%$ in AC, $67.68{\pm}0.55%$ in MC, $96.18{\pm}0.41%$ in MA, respectively. The electron donating ability were significantly difference (p<0.05) between the solvents. The inhibitory activity of glutathione S-transferase in Citrus unshiu extracts were $76.22{\pm}0.65%$ in EA, $31.73{\pm}0.48%$ in MC, $97.48{\pm}0.56%$ in MeOH, respectively. Also, inhibitory activity of glutathione S-transferase in EtOH Citrus unshiu extracts were $75.54{\pm}0.55%$ in EA, $73.53{\pm}0.38%$ in MC, $48.70{\pm}0.46%$ in MeOH, respectively. The inhibitory activity of glutathione S-transferase were significantly difference (p<0.05) between the solvents. These results indicated that the Citrus unshiu extracts is a high-valued food ingredient and the extraction with methanol will be useful as a nutritional source with natural antioxidant activities. Considering high consumer demand beneficial health effects, Citrus unshiu extracts can be utilized to develop functional food health- promoting and natural antioxidant agents.

Effects of glutathione S-transferase M1 and T1 deletions on carbamazepine metabolism among a Tunisian population

Chahra Chbili,Neila Fathallah,Manel Nouira,Aicha Laouani,Anis Hassine,Sana Ben Amor,Sofiene Ben Ammou,Saad Saguem 한국유전학회 2015 Genes & Genomics Vol.37 No.12

Glutathione-S-transferases enzymes are involved in the detoxification of several endogenous and exogenous substances. These genetic pathways could be involved in the therapeutic efficacy and toxic effects of carbamazepine by modulating metabolic profiles. In this present study, we evaluated the effects of two glutathione- S-transferase polymorphisms, GSTM1 and GSTT1, on metabolic phenotype of carbamazepine in a Tunisian population. These polymorphisms were studied in 94 patients with epilepsy, using a polymerase chain reaction. Test U Mann–Whitney was used for analyzing results. The study results demonstrated that individuals with the glutathione- S-transferase M1 null genotype were at an increased risk of toxicity secondary to a relative accumulation of carbamazepine 10,11-epoxide and carbamazepine. Consequently leading to an increase in the plasma concentration of carbamazepine and carbamazepine 10,11- epoxide (P = 0.03, P = 0.01 respectively). Whereas no significant effects were observed between individuals with glutathione-S-transferase M1 or glutathione-S-transferase T1 null genotype and metabolic ratio carbamazepine 10,11-epoxide to carbamazepine (P = 0.40). These genotyping findings revealed that the absence of GSTM1 activity could be a contributor factor for the development of toxic effects of carbamazepine. Such an accumulation would require eventually a dosage adjustment.

Effect of Diallyl Disulfide on the Hepatic Glutathione S-Transferase Activity in Rat : Diallyl Disulfide Effect on the Glutathione S-Transferase

Huh, Keun,Lee, Sang-Il,Park, Jong-Min,Kim, Seok-Hwan The Pharmaceutical Society of Korea 1986 Archives of Pharmacal Research Vol.9 No.4

Glutathione s-transferase in thought to play a key role in initiating the detoxication of potential alkylating agents, including pharmacologically active compounds. It is widely accepted that garlic contained allin which is converted to allicin by allinase. Allicin is easily degraded to diallyl disulfide and other components. This report attempted to observe the effect of diallyl disulfide on some biological activities. It was observed that the activity of serum transaminase was not changed by the treatment of diallyl disulfide. The liver cytosolic glutathione s-transferase was significantly increased. where as the microsomal glutathione s-transferase was not increased.

한국인 신생아 황달과 Glutathione S-transferase 다형성에 관한 연구

강창석,홍승수,김지숙,김은령 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.3

Purpose:Glutathione S-transferase (GST) is a polymorphic supergene family of detoxification enzymes that are involved in the metabolism of numerous diseases. Several allelic variants of GSTs show impaired enzyme activity and are suspected to increase the susceptibility to diseases. Bilirubin is bound efficiently by GST members. The most commonly expressed gene in the liver is GSTM1, and GSTT1 is expressed predominantly in the liver and kidneys. To ascertain the relationship between GST and neonatal hyperbilirubinemia, the distribution of the polymorphisms of GSTT1 and GSTM1 were investigated in this study. Methods:Genomic DNA was isolated from 88 patients and 186 healthy controls. The genotypes were analyzed by polymerase chain reaction (PCR). Results: The overall frequency of the GSTM1 null was lower in patients compared to controls (P=0.0187, Odds ratio (OR) =0.52, 95% confidence interval (CI), 0.31-0.88). Also, the GSTT1 null was lower in patients compared to controls (P=0.0014, OR=0.41, 95% CI=0.24-0.70). Moreover, the frequency of the null type of both, in the combination of GSTM1 and GSTT1, was significantly reduced in jaundiced patients (P=0.0008, OR=0.31, 95% CI=0.17-0.61). Conclusion:We hypothesized that GSTM1 and GSTT1 might be associated with neonatal hyperbilirubinemia. However, the GSTT1 and GSTM1 null type was reduced in patients. Therefore the null GSTT1, null GSTM1, and null type of both in the combination of GSTM1 and GSTT1 may be not a risk factor of neonatal jaundice. (Korean J Pediatr 2008;51:262-266) Purpose:Glutathione S-transferase (GST) is a polymorphic supergene family of detoxification enzymes that are involved in the metabolism of numerous diseases. Several allelic variants of GSTs show impaired enzyme activity and are suspected to increase the susceptibility to diseases. Bilirubin is bound efficiently by GST members. The most commonly expressed gene in the liver is GSTM1, and GSTT1 is expressed predominantly in the liver and kidneys. To ascertain the relationship between GST and neonatal hyperbilirubinemia, the distribution of the polymorphisms of GSTT1 and GSTM1 were investigated in this study. Methods:Genomic DNA was isolated from 88 patients and 186 healthy controls. The genotypes were analyzed by polymerase chain reaction (PCR). Results: The overall frequency of the GSTM1 null was lower in patients compared to controls (P=0.0187, Odds ratio (OR) =0.52, 95% confidence interval (CI), 0.31-0.88). Also, the GSTT1 null was lower in patients compared to controls (P=0.0014, OR=0.41, 95% CI=0.24-0.70). Moreover, the frequency of the null type of both, in the combination of GSTM1 and GSTT1, was significantly reduced in jaundiced patients (P=0.0008, OR=0.31, 95% CI=0.17-0.61). Conclusion:We hypothesized that GSTM1 and GSTT1 might be associated with neonatal hyperbilirubinemia. However, the GSTT1 and GSTM1 null type was reduced in patients. Therefore the null GSTT1, null GSTM1, and null type of both in the combination of GSTM1 and GSTT1 may be not a risk factor of neonatal jaundice. (Korean J Pediatr 2008;51:262-266)

지구자의 Glutathione S-transferase 활성과 알코올 분해효과

차배천,이은희,이은,박행호,Cha, Bae-Cheon,Lee, Eun-Hee,Lee, Eun,Park, Hang-Ho 대한약학회 2004 약학회지 Vol.48 No.3

For the determination of glutathione S-transferase activity, a new method was established by using HPLC system. Moreover, amount of enzyme for a optimum reaction was determined by a comparative study with a variety concentration of enzyme. Using a established method, activity of glutathione S-transferase that is alcohol metabolizing enzyme was investigated on the fruit of Hovenia dulcis Thunb. As the result of experiment, EtOH and $H_2O$ extracts of the fruit of Hovenia dulcis Thunb showed visible a synergistic effect of glutathione S-transferase activity. On a continuous experiment, EtOH and $H_2O$ extracts of the fruit of Hovenia dulcis Thunb showed alcohol decomposition activity on the in vivo test using rat. These results suggest that the fruit of Hovenia dulcis Thunb may be useful in the prevention of hangover.

흰쥐에게 내독소의 비경구 투여가 혈청 및 간의 Glutathione S-transferase, Glutathione peroxidase 및 Glutathione reductase 활성 변동에 미치는 영향

곽춘식,문교철,김상철 啓明大學校 醫科大學 1993 계명의대학술지 Vol.12 No.1

The activities of the cytosolic, microsomal and mitochondrial glutatione S-tranferase (GST) which are detoxifying enzymes in thd liver were measured in order to evaluate the detoxifying ability of the liver to endotoxin. The activities of glutathione peroxidase(GSH-Px), glutathione reductase(GR) in the liver, GST and GR in the serum were also measured. For administration of endotoxin, a dose of 5㎎ of endotoxin (lipopolysaccharide E, coli O26: B6, from Sigma chemical company, USA) per kg of body weight was administered through a right external jugular vein. Then the rats were killed after 3, 8 and 24 hours of injection with endotoxin to measure the activities of the above enzymes in serum and their liver. The activities of the cytosokic and mocrosomal GST in the liver showed a significant decrease between 8 and 24 hours after endotoxin administration, but that of the motochondria showed no signifcant changes throughout the experiment. The activity of the GR in the liver showed a significant decrease at 24 hours after endotoxin adiministration. The activity of the GSH-Px in the liver showed a significant decrease at 8 hours after endotoxin administration. Serum GST and GR activitites showed a signifcant increase between 8 and 24 hours and between 3 and 24 hours after endotoxin administration respectively. According to the results, cytosolic GST and hepatic GR leak into the blood through the damaged membrane of hepatocyte. And it is suggested that the synthesis of the microsomal GST in the liver is decreased.