• 대한한의학회지
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• 제42권4호
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• pp.10-24
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• 2021

Objectives: Yongdamsagan-tang (YST) and Paljung-san (PJS) in traditional medicine and finasteride in modern medicine are used to treat benign prostatic hyperplasia (BPH). In recent, the use of combination herbal remedies with conventional drugs has been increasing. Therefore, we investigated the anti-inflammatory effects of these drugs to treat BPH and the influence of herbal formulas on finasteride metabolism. Methods: The inhibitory effects of the herbal formulas and finasteride on the production of inflammatory mediators and cytokines were determined in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Additionally, the influence of herbal formulas on activities of human drug metabolizing enzymes (DMEs) was assessed using human microsomal enzymes. Results: We observed that YST, PJS and finasteride inhibited the production of nitric oxide (NO), prostaglandin E₂ (PGE₂) and interleukin-6 (IL-6) in RAW 264.7 cells. The half maximal inhibitory concentration (IC₅₀) of YST on PGE₂ production was calculated to be below 25 ㎍/mL. YST inhibited the activity of uridine diphosphate-glucuronosyltransterase (UGT) 1A4 with an IC₅₀ value of 49.35 ㎍/mL. The activities of cytochrome P450 (CYP) 1A2, CYP2B6, CYP2C19, CYP3A4, and UGT1A1 were inhibited by PJS (IC₅₀ < 100 ㎍/mL, each). Although PJS and YST inhibited the activities of CYP3A4 and UGT1A4, respectively, these formulas may not influence the metabolism of finasteride because the IC₅₀ values of herbal formulas on DMEs are too high to affect metabolism. Conclusions: Our results suggest that the combination of finasteride and YST or PJS might not influence their drug metabolism and that the drugs may have synergistic effects against BPH.

• 약학회지
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• 제23권2호
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• pp.111-118
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• 1979

It was previously reported that cytochrome P$_{450}$ content in liver was increased when Capsicum acetone extract was given chronically to rats. The present study is aimed to investigate the effect of capsaicin, a principal component of red pepper, on the drug metabolizing enzymes in rat liver. Capsaicin (5mg/kg) was given intraperitoneally once a day for seven days and zoxazolamine paralysis time and hexobarbital sleeping time were determined 24 hrs after the last dose of capsaicin. Plasma hexobarbital concentration was also determined five and 15 min after hexobarbital administration to rats. Zoxazolamine paralysis time and hexobarbital sleeping time were shortened by 31.6% and 37.1%, respectively, compared with control group. Plasma hexobarbital concentration was lowered by 26.2% after five min and by 35.2% after 15 min, respectively, compared with control group. However, administration of single dose of capsaicin did not affect the zoxazolamine paralysis time and hexobarbital sleeping time. Microsomal cytochrome P$_{450}$ content and NADPH-cytochrome C reductase activity were increased by 14.6% and 11.6%, respectively in the rats pretreated with capsaicin for seven days, while cytochrome b$_{5}$ content was not changed. These results suggest that treatment with capsaicin for seven days may induce the drug metabolizing enzyme in rat liver.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.109-109
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• 2001

The present study was done to investigate the relationship between Kupffer cells and alteration of cytochrome P-450 (CYP)-dependent drug metabolizing enzyme activities during polymicrobial sepsis. Male rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP) followed by fluid resuscitation. The gadolinium chloride (GdC1$_3$, 10 mg/kg), blocker of Kupffer cells, was pretreated intravenously at 48 h and 24 h prior to the induction of CLP. All assay parameters were determined at 24 h after CLP or sham operation. In CLP-treated rats, the mortality rate of animals increased to 50% and serum alanine (ALT) and aspartate aminotransferase (AST) levels also significantly elevated. However, this increase was not suppressed by GdC1$_3$ pretreatment. Microsomal lipid peroxidation markedly increased after CLP operation. This increase was significantly attenuated by pretreatment. Total cytochrome P-450 content and NADPH-cytochrome P-450 reductase activity were not changed after CLP operation, but GdC1$_3$pretreatment reduced total cytochrome P-450 content, The hepatic microsomal CYP 1A1, 1A2, 2Bl and 2El activities in CLP-induced rats were also not significantly different from sham-operated rats. However, GdC1$_3$pretreatment showed a moderate increase in CYP1A1 and 1A2 activities. Our findings suggest that Kupffer cells may be partly responsible for producing hepatocellular dysfunction during sepsis.

• Journal of Preventive Medicine and Public Health
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• 제42권6호
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• pp.360-370
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• 2009

Genetic factors clearly play a role in carcinogenesis, but migrant studies provide unequivocal evidence that environmental factors are critical in defining cancer risk. Therefore, one may expect that the lower availability of substrate for biochemical reactions leads to more genetic changes in enzyme function; for example, most studies have indicated the variant MTHFR genotype 677TT is related to biomarkers, such as homocysteine concentrations or global DNA methylation particularly in a low folate diet. The modification of a phenotype related to a genotype, particularly by dietary habits, could support the notion that some of inconsistencies in findings from molecular epidemiologic studies could be due to differences in the populations studied and unaccounted underlying characteristics mediating the relationship between genetic polymorphisms and the actual phenotypes. Given the evidence that diet can modify cancer risk, gene-diet interactions in cancer etiology would be anticipated. However, much of the evidence in this area comes from observational epidemiology, which limits the causal inference. Thus, the investigation of these interactions is essential to gain a full understanding of the impact of genetic variation on health outcomes. This report reviews current approaches to gene-diet interactions in epidemiological studies. Characteristics of gene and dietary factors are divided into four categories: one carbon metabolism-related gene polymorphisms and dietary factors including folate, vitamin B group and methionines; oxidative stress-related gene polymorphisms and antioxidant nutrients including vegetable and fruit intake; carcinogen-metabolizing gene polymorphisms and meat intake including heterocyclic amins and polycyclic aromatic hydrocarbon; and other gene-diet interactive effect on cancer.

• 한국식품영양과학회지
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• 제29권2호
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• pp.268-273
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• 2000

To investigate an effect of the ethanol extract of Lycium chinense(EELC) on the activities of enzymes scavenging oxygen free radicals or detoxicating alcohol. The ground Lycium chinense was extracted with 30% edible ethanol and then diluted with 6% ethanol to contain 2% EELC(w/v). Three different groups of male Sprague-Dawley rats had taken a drink EELC, ethanol(ETH) or water(control), respectively for 2 months. At the end of experimental period, the animals were sacrificed and obtained the following findings. The EELC-treated animals showed the highest activity of hepatic glucose-6-phosphatase among three groups. The activities of xanthine oxidase and cytochrome p-450 from EELC treatment group were lower than those from ETH-treated group. However, the activity of superoxide dismutase was higher in the EELC-treated group than the ETH-treated(p<0.005). Furthermore, hepatic alcohol or aldehyde dehydrogenase activity, and glutathione content and glutathione peroxidase were significantly higher in EELC-treated animals than in ETH-treated those. The activity of glutathione S-transferase in liver was appeared the orderly higher value in EELC, ETH and control-treated group. As the result, EELC may affect the reduction of oxygen free radical production and help the detoxication of ethanol.

• Environmental Analysis Health and Toxicology
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• 제21권2호
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• pp.103-113
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• 2006

This study examined effects of crude oil on the phase II drug-metabolizing enzymes UDP-glucuronosyl transferase (UDPGT) and glutathione S-transferase (GST) in mussel Mytilus edulis and rockfish Sebastes schlegeli, a representative bivalve and a culture fish, respectively. This work also intended indirectly to evaluate the post impact recovery from the massive oil tanker spillage accidents occurred during the summer of 1995 in the sea area off Yosu City, Chonnam. For these, enzyme activities of UDPGT and GST were examined in the fish and mussel following laboratory exposure to fresh crude oil, weathered oil, field-obtained oil residues, or in the field biota samples. Decreased GST activity was observed in rock fish following exposure to oil-soluble fraction (OSF) of fresh oil. A similar diminished GST activity was also observed after OSF of artificially weathered oil. OSF of field oil residues retrieved from the spillage area approximately 1 year later also exerted a slight inhibition of GST to rockfish. There was neither a change in UDPGT in rockfish, nor were there changes in mussel in both enzymes to any oil fractions. We could not observe any difference in the two enzymes either in rockfish or mussel sampled from the field during $1.5{\sim}2.0$ years post spillage, indicating that their enzyme systems might had been recovered by the sampling time. In conclusion, it seems that the inhibition of GST activity in rockfish is a biomarker response to crude oil exposure. The results, however, must be interpreted with care, as the inhibition nay reflect various factors such as oil concentration, duration and water temperature.

• Toxicological Research
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• 제17권
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• pp.299-304
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• 2001

Xenobiotics and their reactive intermediates bind to cellular macromolecules and/or generate oxidative stress. which provoke deleterious effects on the cell function. Induction of xenobiotic-biotrans-forming enzymes and antioxidant molecules is an important defense mechanism against such insults. A group of genes involved in the defense mechanism. e.g. genes encoding glutathione S-transferases. NAD(P)H: quinone oxidoreductase, UDP-glucuronosyltransferase (UDP-GT) and ${\gamma}$-glutamylcysteine synthetase (GGCS). have a common regulatory sequence, Antioxidant or Electrophile Responsive Element (ARE/EpRE). Recently. Nrf2. discovered as a homologue of erythroid transcription factor p45 NF-E2, was shown to bind ARE/EpRE and induce the expression of these defense genes. Mice that lack Nrf2 show low basal levels of expression and/or impaired induction of these genes. which makes the animals highly sensitive to xenobiotic toxicity. Indeed. we show here that nrf2-deficient mice had a higher mortality than did the wild-type mice when exposed to acetaminophen (APAP). Detailed analyses of APAP hepatotoxicity in the nrf2 knockout mice indicate that a large amount of reactive APAP metabolites was generated in the livers due to the impaired basal expression of two detoxifying enzyme genes, UDP-GT (Ugt1a6) and GGCS. while the cytochrome P450 content was unchanged. Thus. the studies using the nrf2 knockout mice clearly demonstrate significance of the expression of Nrf2-regulated enzymes in protection against xenobiotic toxicity.

• 약학회지
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• 제48권3호
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• pp.213-217
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• 2004

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.

• 생명과학회지
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• 제21권6호
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• pp.811-818
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• 2011

해조류 매생이의 기능성을 증명하기 위하여 열수 또는 에탄올 추출하여 여러 가지 생리활성에 대하여 조사하였다. 우선, 매생이 열수와 에탄올 추출물의 항산화능을 조사하기 위하여 DPPH radical 소거능, SOD 유사활성을 측정하였다. 그 결과, 매생이 열수와 에탄올 추출물의 농도가 증가함에도 불구하고 낮은 증가율을 보였는데, 10 mg/ml에서 DPPH radical 소거능은 각각 10.8, 62.4%, SOD 유사활성은 각각 13.8, 27.1%로 나타났다. 항고혈압 활성 측정에서는 1 mg/ml의 매생이 열수와 에탄올 추출물이 각각 5.9, 49.7%의 활성을 보여 비교적 높은 효능이 매생이 에탄올 추출물에서 나타났다. 매생이 열수와 에탄올 추출물의 혈당 강하 효과는 ${\alpha}$-glucosidase 저해능 분석으로 측정하였는데, 1 mg/ml 농도의 매생이 열수와 에탄올 추출물은 각각 1.4, 67.3%로써 비교적 높은 효능을 매생이 에탄올 추출물에서 보였다. 매생이의 숙취해소 효능은 ADH와 ALDH 활성증진에 매생이 열수와 에탄올 추출물이 미치는 영향을 조사함으로써 증명하고자 하였다. 그 결과, 매생이 열수와 에탄올 추출물의 농도가 증가함에도 불구하고 알콜 분해능 증가율이 낮게 나타났으며, 심지어 acetaldehyde 분해능은 관찰되지 않았다. Elastase 억제 효능 분석에서는 매생이 열수와 에탄올 추출물 10 mg/ml에서 각각 75.9, 51.2%로 나타났다.

• 한국약용작물학회지
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• 제10권1호
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• pp.29-36
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• 2002

예로부터 우리나라와 중국을 비롯한 동양에서는 음양곽을 강정제 및 정력강화제로 사용되어왔다. 본 연구는 흰쥐에게 장기간 음양곽 물 추출물을 공급하고(0.025%,w/v) 노화에 따른 생리적인 변화와 간의 이물질 대사 효소군의 활성도에 미치는 영향을 조사하였다. 흰쥐에 음양곽의 물 추출물 공급으로 특이한 질병은 발견되지 않았으나 24개월에서 간과 신장의 무게는 대조군에 비해 다소 증가하였으며 혈청의 glutamate-oxaloacetate transminase와 glutamate-pyruvate transminase 활성도도 증가하였다 간의 이물질 대사효소 중 cytochrome P450 NADPH-cytochrome P450 reductase, benzphetamine N-demethylase ethoxycoumarine O-deethylase, glutathione S-transferase의 활성도는 두 그룹 모두 노화에 따라 감소하였으며, 음양곽 물 추출물 투여에 의해 감소현상이 악화되었다. 간의 cytochrome B5의 함량과 NADH cytochrome b5 reductase의 활성도도 노화에 따라 감소되었으나 같은 나이에서 두 그룹간의 뚜렷한 차이를 보이지 않았다. 이상의 결과로 보아 흰쥐에 장기간 음양곽 물 추출물을 공급은 노년기에 노화에 따라 감소하는 간의 이물질 대사 기능에 부담을 수도 있다는 것을 암시해 준다.