Nrf2-mediated Induction of Phase 2 Detoxifying Enzymes by Curled Dock (Rumex crispus L.) Seed Extract

Hyo Jung Kim,정채림,박인실,서화진,권오운,김정상 한국식품과학회 2013 Food Science and Biotechnology Vol.22 No.3

Curled dock (Rumex crispus L.) is known to have several health benefits including antioxidant, antifungal,and anti-inflammatory effects. The potential to induce phase 2 detoxifying enzymes of butanol extract of curled dock (BECD) seeds was investigated. BECD increased the activity of NAD(P)H:quinone oxidoreductase and expression of phase 2 detoxifying enzymes such as heme oxygenase 1, γ-glutamylcysteine synthetase, NAD(P)H:quinone oxidoreductase,and glutathione reductase, in both hepa1c1c7 and its mutant BPRc1 cells. The translocation of transcription factor nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and binding to antioxidant response element (ARE) in the promoter region of phase 2 detoxifying/antioxidant enzymes were promoted by BECD in HepG2-C8 cells. Furthermore,BECD enhanced phosphorylation of Akt in hepatoma cell lines while Nrf2 activation induced by BECD was suppressed by an inhibitor of Akt. This result suggests that BECD induces phase 2 detoxifying enzymes through the Akt/Nrf2/ARE signaling pathway. BECD merits further study to be developed as detoxification agent.

황기(黃耆) 약침액(藥鍼液)의 Glutathione S-transferase 와 NAD(P)H: Quinone Reductase 유도

류준선 ( Jun Seon Ryu ),임종국 ( Jong Kook Lim ) 대한경락경혈학회 2001 Korean Journal of Acupuncture Vol.18 No.1

발암물질을 무독화시키는 QR 생성 유도를 살펴보기 위하여 황기 약침액 및 열수추출액을 생쥐의 간암세포인 Hepa1c1c7에 처리하여 측정한 결과, 황기 약침액의 농도를 증가시킬수록 많은 QR 생성율을 보였으며, GSH 생성이 증가하였고, GST 생성 또한 증가하였다. Induction of phase Ⅱ enzymes such as quinone reductase (QR) or glutathione S-transferase (GST) is considered a major mechanism of protection against initiation of carcingenesis. This study was desinged to investigate the potential of Astragali Radix Aqua-acupuncture Solution (ARAS) to induce phase Ⅱ enzymes and glutathione (GSH) in murine hepatoma cells grown in microtiter plate wells. ARAS was potent inducers of QR activity. ARAS was induced about 2.6-fold at concentration of 5×. In addition, GST activity was increased with ARAS. GSH levels were increased about 1.2-fold with ARAS at concentration of 0.1×. These results suggested that ARAS may act as blocking agents against carcinogenesis by induction of phase Ⅱ marker enzymes.

생약(生藥) 약침액(藥鍼液)이 암예방(癌豫防) 효소계(酵素系)에 미치는 영향(影響)

임종국 ( Jong Kook Lim ),문진영 ( Jin Young Moon ),조경희 ( Kyoung Hee Cho ),손윤희 ( Yun Hee Shon ),남경수 ( Kyung Soo Nam ) 대한경락경혈학회 2000 Korean Journal of Acupuncture Vol.17 No.1

금은화, 당귀, 감두를 이용하여 조제한 각각의 약침액을 이용하여 암예방효과를 살펴 보았다. 발암물질을 무독화시키는 QR 생성 유도를 생쥐의 간암세포인 Hepa1c1c7과 측정하였으며, 그 결과 금은화 약침액, 당귀 약침액, 감두약침액을 처리한 Hepa1c1c7에서 QR생성이 유도되었으며 GSH 생성을 살펴본 결과 Hepa1c1c7세포에서 실험에 이용된 모든 생약 약침액에 의한 GSH 생성이 증가하였고, GST 생성 또한 증가하였다. Induction of phase Ⅱ enzymes such as quinone reductase (QR) or glutathione S-transferase (GST) is considered a major mechanism of protection against initiation of carcingenesis. The induction of detoxification enzymes and glutathione were studied with Lonicerae Flos aqua-acupuncture solution (LFAS), Angelicae gigantis Radix aqua-acupuncture solution (AGRAS), and Gamdutang aqua-acupunture solution (GAS) in murine hepatoma cells grown in microtiter plate wells. LFAS, AGRAS and GAS were potent inducers of QR activity. LFAS was induced about 2.6-fold at concentration of 3×. AGRAS and GAS were also induced about 2.6-, 1.8-fold at concentration of 5×, respectively. In addition, GST activity was increased with LFAS, AGRAS, and GAS. GSH levels were increased about 2-fold with LFAS at concentration of 5×, 1.3-fold with AGRAS at concentration of 3×, and 1.2-fold with GAS at concentration of 5×. These results suggested that LFAS, AGRAS, and GAS may act as blocking agents against carcinogenesis by induction of phase Ⅱ marker enzymes.

Regulation of Phase II Enzymes by Genistein and Daidzein in Male and Female Swiss Webster Mice

Erik B. Froyen,Jaime L. Rudolf Reeves,Alyson E. Mitchell,Francene M. Steinberg 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.6

The consumption of soy and soy isoflavones has been associated with a decreased risk of certain cancers. A factor contributing to this dietary chemoprevention is the activity of phase I and II biotransformation enzymes. This study evaluated the hypothesis that dietary soy isoflavones will increase hepatic and extrahepatic quinone reductase (QR), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) phase II enzyme activities, under short-term feeding and basal (non–pharmacologic-induced) conditions. Male and female Swiss Webster mice were fed for 1, 3, 5, or 7 days of one of four treatments: control (casein AIN-93G) or control supplemented with flavone (positive control), genistein, or daidzein aglycones at 1,500mg/kg of diet. QR activity was increased by daidzein in the liver, by both isoflavones in the kidney and small intestine, and by genistein in the heart. Genistein and daidzein slightly decreased UGT activities in some tissues. Liver GST activity was decreased by genistein in females. In contrast, genistein and daidzein increased kidney GST activity. In general, the greatest effects of isoflavones on phase II enzymes were observed in liver and kidney tissues, occurring at day 3, and peaking at day 5. Sex effects in the liver and kidney included females exhibiting higher QR activities and males exhibiting higher UGT and GST activities. In conclusion, individual soy isoflavones modulate phase II enzymes in mice under short-term feeding and basal conditions. This study provides insights into the actions of isolated isoflavones in mice.

석창포(石菖蒲) 약침액(藥鍼液)의 암(癌) 예방(豫防)관련 효소 유도 효과

노동일 ( Dong Il Roh ),임종국 ( Jong Kook Lim ) 대한경락경혈학회 2002 Korean Journal of Acupuncture Vol.19 No.2

발암물질을 무독화시키는 QR 생성 유도를 살펴보기 위하여 석창포 약침액 및 열수추출액을 생쥐의 간암세포인 Hepa1c1c7에 처리하여 측정한 결과, 석창포 약침액의 농도를 증가시킬수록 높은 QR 생성율을 보였으며, QR 활성 유도효과 보다는 낮았지만 GSH와 GST 생성도 증가하였다. Induction of phase Ⅱ enzymes such as quinone reductase (QR) and glutathione S-transferase (GST) is considered a major mechanism of protection against initiation of carcinogenesis. The present study was performed to evaluate the chemopreventive activity of Acori Graminei Rhizoma aqua-acupuncture solution (AGRAS) and Acori Graminei Rhizoma water-extracted solution (AGRWS) by measuring the induction of phase II enzymes. AGRAS and AGRWS are potent inducers of quinone reductase activity in murine hepatoma Hepa1c1c7 cells. The levels of GSH and GST was increased sightly with AGRAS and AGRWS. These results suggest that AGRAS and AGRWS may act as blocking agents against carcinogenesis by induction of phase Ⅱ enzymes.

Strawberry Consumption Is Associated with Increased Antioxidant Capacity in Serum

Susanne M. Henning,Navindra P. Seeram,Yanjun Zhang,,Kun Gao,Ru-Po Lee,David C. Wang,Alona Zerlin,Hannah Karp,Gail Thames,Jenny Kotlerman,Zhaoping Li,David Heber 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.1

Strawberries are known to contain antioxidants, but the significance of ingesting antioxidant-rich fruits remains to be established. In order to determine whether the consumption of strawberries impacted measures of in vivo antioxidant capacity, frozen strawberries (250g) were administered daily for 3 weeks to 21 healthy female volunteers. Compliance was confirmed by quantitating pelargonidin-glucuronide, urolithin A-glucuronide, and 2,5-dimethyl-4-hydroxy-3-[2H]furanone-glucuronide in plasma and urine by liquid chromatography–mass spectrometry and antioxidant capacity in serum measured by the increase in lag phase of low-density lipoprotein after copper sulfate exposure, DNA strand breaks in lymphocytes, and activity of phase II enzymes. Among these measures lipid peroxidation lag time increased by 20% (P<.01), whereas other measures did not change significantly. The potent antioxidant defenses in humans make determination of changes due to dietary ingestion in healthy individuals difficult. In summary, daily consumption of strawberries resulted in a modest but significant increase in antioxidant capacity in a healthy population.

천궁(川芎) 약침액(藥鍼液)과 열수추출액의 생체해독효소 유도 효과

한상훈 ( Sang Hoon Han ),임종국 ( Jong Kook Lim ) 대한경락경혈학회 2001 Korean Journal of Acupuncture Vol.18 No.2

발암물질을 무독화시키는 QR 생성 유도를 살펴보기 위하여 川芎 약침액 및 열수추출액을 생쥐의 간암세포인 Hepa1c1c7에 처리하여 측정한 결과, 황기 약침액의 농도를 증가시킬수록 많은 QR 생성율을 보였으며, GST 생성 또한 증가하였다. Induction of phase Ⅱ, enzymes such as quinone reductase (QR) or glutathione S-transferase (GST) is considered a major mechanism of protection against initiation of carcingenesis. The present study was performed to evaluate the chemopreventive activity of Cnidium officinale Makino aqua-acupuncture solution (COMAS) and Cnidium officinale Makino water-extracted solution (COMWS) in vitro. COMAS and COMWS are potent inducer of quinone reductase and glutathioe S-transferase activities in murine hepatoma Hepa1c1c7 cells. However, GSH activity was not increased with COMAS and COMWS. These results suggest that COMAS and COMWS may act as blocking agents against carcinogenesis by induction of phase Ⅱ enzymes.

Induction of Anticarcinogenic Enzymes by Dichloromethane-soluble Fraction of Physalis alkekengi var. francheti Hort. in Mouse Hepatoma Cells

Seo, JiYeon,Kim, Hyo Jung,Kim, Jong-Sang Institute of Agricultural Science and Technology 2014 慶北大農學誌 Vol.32 No.3

Physalis alkekengi var. francheti Hort. is known as an insecticide and traditional remedy for liver related diseases. Therefore, this study investigated the chemopreventive effects of extracts and several solvent fractions (n-hexane, dichloromethane, n-butanol, water) of Physalis alkekengi var. francheti Hort. First, their cytotoxicity and NQO1 activity were measured using an MTT assay, plus a quinone reductase [NAD(P)H dehydrogenase (quinone); NAD(P)H: (quinone acceptor) oxidoreductase, EC 1.6.99.2]-inducing activity assay was performed using cultured murine hepatoma cells (Hepa1c1c7) and its mutant cells(BpRc1). The reduction of electrophilic quinones by NQO1 is an important detoxification pathway and major mechanism of chemoprevention. When compared with the other solvent soluble fractions with different polarities, the dichloromethane fraction of Physalis alkekengi var. francheti Hort. showed a higher NQO1-inducing activity that was also dose-dependent. Moreover, the dichloromethane fraction of Physalis alkekengi var. francheti Hort. induced ARE-luciferase activities in HepG2-C8 cells that were generated by transfecting the ARE-luciferase gene construct, suggesting the Nrf2-ARE-mediated induction of anti-oxidative enzymes. In conclusion, the dichloromethane-soluble fraction of Physalis alkekengi var. francheti Hort. showed a relatively strong induction of detoxifying enzymes, thereby meriting further study to identify the active components and evaluate their potential as cancer preventive agents.

Induction of Anticarcinogenic Enzymes by Dichloromethane-soluble Fraction of Physalis alkekengi var. francheti Hort. in Mouse Hepatoma Cells

Seo, JiYeon,Kim, Hyo Jung,Kim, Jong-Sang 경북대학교 농업생명과학대학 2014 Current Research on Agriculture and Life Sciences Vol.32 No.3

Physalis alkekengi var. francheti Hort. is known as an insecticide and traditional remedy for liver related diseases. Therefore, this study investigated the chemopreventive effects of extracts and several solvent fractions (n-hexane, dichloromethane, n-butanol, water) of Physalis alkekengi var. francheti Hort. First, their cytotoxicity and NQO1 activity were measured using an MTT assay, plus a quinone reductase [NAD(P)H dehydrogenase (quinone); NAD(P)H: (quinone acceptor) oxidoreductase, EC 1.6.99.2]-inducing activity assay was performed using cultured murine hepatoma cells (Hepa1c1c7) and its mutant cells(BpRc1). The reduction of electrophilic quinones by NQO1 is an important detoxification pathway and major mechanism of chemoprevention. When compared with the other solvent soluble fractions with different polarities, the dichloromethane fraction of Physalis alkekengi var. francheti Hort. showed a higher NQO1-inducing activity that was also dose-dependent. Moreover, the dichloromethane fraction of Physalis alkekengi var. francheti Hort. induced ARE-luciferase activities in HepG2-C8 cells that were generated by transfecting the ARE-luciferase gene construct, suggesting the Nrf2-ARE-mediated induction of anti-oxidative enzymes. In conclusion, the dichloromethane-soluble fraction of Physalis alkekengi var. francheti Hort. showed a relatively strong induction of detoxifying enzymes, thereby meriting further study to identify the active components and evaluate their potential as cancer preventive agents.

Chemopreventive effects of polysaccharides extract from Asterina pectinifera on HT-29 human colon adenocarcinoma cells

( Kyung Soo Nam ),( Yun Hee Shon ) 생화학분자생물학회 2009 BMB Reports Vol.42 No.5