• 생명과학회지
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• 제28권2호
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• pp.247-256
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• 2018

심혈관계 질환은 질환별 사망률 순위에 있어서 세계에서는 1위이며, 우리나라에서는 2위인 질병이다. 심혈관계 질환 발생의 주 위험 요인인 콜레스테롤은 HMG-CoA reductase에 의해 간에서 신생합성이 조절된다. 현재 고콜레스테롤혈증 치료에 statin이 널리 사용되고 있지만 광범위한 부작용이 보고되고 있어서 이를 대체하거나 보조할 수 있는 천연물 유래의 기능성 물질 개발이 필요한 실정이다. 따라서 본 연구에서는 혈장 콜레스테롤 감소 활성을 가지는 물질을 발굴하고자 98종의 플라보노이드 및 그와 관련된 화합물들을 대상으로 $10{\mu}g/ml$ 농도에서 HMG-CoA reductase 저해 활성을 탐색하였다. 그 결과, sophoraflavanone G, morin, 및 kuraridin이 각각 54.6%, 45.04% 및 21.9%의 저해활성을 타내었으며, $IC_{50}$값을 계산한 결과, sophoraflavanone G가 $7.3{\mu}g/ml$로 가장 낮았으며 morin과 kuraridin은 각각 $13.3{\mu}g/ml$과 $87.4{\mu}g/ml$으로 확인되어, 향후 고콜레스테롤혈증 예방 및 치료제의 가능성을 제시하였다.

• 대한약리학회지
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• 제31권3호
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• pp.377-384
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• 1995

연교액기스가 창상치료제로서의 사용가능성을 검증하기 위하여 연교의 창상치유 효과와 독성에 대하여 조사하였으며 아울러 연교액기스가 항생작용이 있는지도 조사하였다. 연교의 창상치유 효과를 Tetrachlorodecaoxygen anion complex(TCDO) 및 단백질을 제거한 혈액투석액(Haemyl)과 생리식염수의 창상치료 효과와 비교하였다. 4일, 11일, 14일째의 창상면적은 연교액기스, TCDO, Haemyl의 치료에 의하여 대조구인 생리식염수의 치료구에 비해 유의하게 적었다. 그러나 8일째의 창상면적은 다만 연교액기스의 치료구만 유의하게 적었다. 조직학적 검사에서도 연교액기스, TCDO, Haemyl의 치료구가 생리식염수의 치료구에 비해 표피화가 촉진되었다. 간 효소활성도(GOT, GPT), 혈구의 수에 있어서 연교액기스의 투여가 대조구에 비하여 어떤 유의적 차이가 보이지 않았으며 그외에도 연교액기스는 병원균의 증식을 억제하지 않았다. 이런 결과들은 연교액기스가 장차 창상 치료제로서의 개발 가능성이 시사하였으며 그의 약리작용은 항생작용과 무관한 것으로 추정된다.

• 한국수정란이식학회지
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• 제28권2호
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• pp.157-162
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• 2013

Methoxychlor (MXC) was developed to be a replacement for the banned pesticide DDT. HPTE [2,2-bis (p-hydroxyphenyl)-1,1,1-trichloroethane], which is an in vivo metabolite of MXC, has strong oestrogenic and anti-androgenic effects. MXC and HPTE are thought to produce potentially adverse effects by acting through oestrogen and androgen receptors. Of the two, HPTE binds to sex-steroid receptors with greater affinity, and it inhibits testosterone biosynthesis in Leydig cells by inhibiting cholesterol side-chain cleavage enzyme activity and cholesterol utilisation. In a previous study, MXC was shown to induce Leydig cell apoptosis by decreasing testosterone concentrations. I focused on the effects of MXC on male mice that resulted from interactions with sex-steroid hormone receptors. Sex-steroid hormones affect other organs including the kidney and liver. Accordingly, I hypothesised that MXC can act through sex-steroid receptors to produce adverse effects on the testis, kidney and liver, and I designed our experiments to confirm the different effects of MXC exposure on the male reproductive system, kidney and liver. In these experiments, I used pre-pubescent ICR mice; the puberty period in ICR mice is from postnatal day (PND) 45 to PND60. I treated the experimental group with 0, 100, 200, 400 mg MXC/kg b.w. delivered by an intra-peritoneal injection with sesame oil used as vehicle for 4 weeks. At the end of the experiment, the mice were sacrificed under anaesthesia. The testes and accessory reproductive organs were collected, weighed and prepared for histological investigation. I performed a chemiluminescence immune assay to observe the serum levels of testosterone, LH and FSH. Blood biochemical determination was also performed to check for other effects. There were no significant differences in our histological observations or relative organ weights. Serum testosterone levels were decreased in a dose-dependent manner; a greater dose resulted in the production of less testosterone. Compared to the control group, testosterone concentrations differed in the 200 and 400 mg/kg dosage groups. In conclusion, I observed markedly negative effects of MXC exposure on testosterone concentrations in pre-pubescent male mice. From our biochemical determinations, I observed some changes that indicate renal and hepatic failure. Together, these data suggest that MXC produces adverse effects on the reproductive system, kidney and liver.

• Clinical and Experimental Reproductive Medicine
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• 제29권3호
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• pp.215-222
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• 2002

Objective : Previous studies have suggested that hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR C677T) mutations are associated with increased risk of recurrent spontaneous abortion (RSA). Recently, a second site polymorphism in MTHFR, 1298A-->C, which changes a glutamic acid into an alanine residue, was shown to be associated with a decreased enzyme activity. We tested whether the variant alleles of MTHFR C677T and A1298C are risk factor (biomarker) for RSA. Materials and Methods: We analyzed DNA from a case-control study in the Korean DNA was extracted from blood samples of 118 patients with RSA and 123 healthy fertile patients as the controls. MTHFR variant alleles were determined by a PCR-restriction fragment length polymorphism assay. Results: We found no evidence for an association between 677TT genotype and risk of RSA (OR=1.95, 95% CI=$0.84{\sim}4.50$, p=0.12). However, the MTHFR 1298AC (OR=0.36, 95% CI=$0.20{\sim}0.63$, p=0.0004) and 1298AC+CC (OR=0.35, 95% CI=$0.20{\sim}0.61$, p=0.0002) genotypes were lower among 118 RSA cases compared with 123 controls, conferring a 2.8-fold decrease in risk of RSA, respectively. Moreover, the combined genotypes of MTHFR 677CC/1298AC (OR=0.30, 95% CI=$0.10{\sim}0.88$, p=0.029) and 677CT/1298AC (OR=0.77, 95% CI=$0.60{\sim}0.99$, p=0.043) also showed significantly lower risk than those with MTHFR 677CC/1298AA type. Conclusion: MTHFR 1298AC, MTHFR 677CC/1298AC and 677CT/1298AC genotypes may represent genetic markers for the protection of RSA at least in Korean women.

• 대한약침학회지
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• 제19권1호
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• pp.37-44
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• 2016

Objectives: This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide-co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo[a]pyrene (BaP)]-induced lung cancer in mice in vivo. Methods: dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. Results: The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Conclusion: Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer.

• Journal of Microbiology and Biotechnology
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• 제20권9호
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• pp.1331-1338
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• 2010

This study was designed to investigate the potentially protective effects of Curcuma longa Linn. extract (CLE) on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in rats. Male Sprague-Dawley rats were pretreated with 50 or 100mg/kg of CLE or 100mg/kg of butylated hydroxytoluene(BHT) for 14 days before $CCl_4$ administration. In addition, the CLE control group was pretreated with 100mg/kg CLE for only 14 days. Three hours after the final treatment, a single dose of $CCl_4$ (20mg/kg) was administrated intraperitoneally to each group. After the completion of this phase of the experiment, food and water were removed 12 h prior to the next step. The rats were then anesthetized by urethane and their blood and liver were collected. It was observed that the aspartate aminotransferase and alanine aminotransferase activities of the serum, and the hepatic malondialdehyde levels had significantly decreased in the CLE group when compared with the $CCl_4$-treated group. The antioxidant activities, such as superoxide dismutase, catalase, and glutathione peroxidase activities, in addition to glutathione content, had increased considerably in the CLE group compared with the $CCl_4$-treated group. Phase II detoxifying enzymes, such as glutathione S-transferase, were found to have significantly increased in the CLE group as opposed to the $CCl_4$-treated group. The content of Nrf2 was determined by Western blot analysis. Pretreated CLE increased the level of nuclear translocated Nrf2, and the Nrf2 then increased the activity of the antioxidant and phase II detoxifying enzymes. These results indicate that CLE has protective effects against $CCl_4$-induced hepatotoxicity in rats, via activities of antioxidant and phase II detoxifying enzymes, and through the activation of nuclear translocated Nrf2.

• 한국식품과학회지
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• 제31권4호
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• pp.1101-1108
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• 1999

대두가수분해물 분무건조 펩타이드(SoyPep)가 자발성고혈압 횐쥐(spontaneously hypertensive rat, SHR)의 혈중지질수준, 생화학적지표 및 조직병리학적 변화에 미치는 영향을 조사하였다. SHR을 무작위로 대조군, 3% SoyPep 투여군, 10% SoyPep 투여군으로 구분하여 8주동안 실험사육하였다. 혈중지질 및 항산화성 비타민 수준, GOT 및 GPT활성을 측정하였고, 신장, 혈관조직, 혈장중 ACE 활성을 측정하였다. 또한, 각 주요장기의 조직병리학적 변화를 검토하였다. 식이 SoyPep은 SHR의 혈중 중성지질, 총콜레스테롤, LDL-콜레스테롤을 저하시키며, 또한, ACE저해활성 및 혈중 지질 수준의 개선작용을 나타내는 것이 확인되었다. 이들 결과로 보아, 대두 펩타이드는 혈중 지질수준의 증가를 수반하는 질병의 예방을 위한 새로운 기능성 식품소재로서의 활용가치가 매우 높을 것으로 기대된다.

• Archives of Pharmacal Research
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• 제26권11호
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• pp.967-973
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• 2003

Cytochrome P4502C9(CYP2C9) is largely responsible for terminating anticoagulant effect by hydroxylation of S-warfarin to inactive metabolites. Mutations in the CYP2C9 gene result in the expression of allelic variants, CYP2C9*2 and CYP2C9*3 with reduced enzyme activity compared to wild type CYP2C9 *1. The aim of this study was to assess relationship between requirement of warfarin dose and polymorphism in CYP2C9 in Korean population. Patients on warfarin therapy for longer than 1 year were included from July 1999 to December 2000 and categorized as one of four groups; regular dose non-bleeding, regular dose bleeding, low dose non-bleeding and low dose bleeding. Low dose was defined as less than 10 mg/week for 3 consecutive monthly follow-ups. Bleeding complications included minor and major bleedings. Blood samples were processed for DNA extraction, genotyping and sequencing to detect polymorphism in CYP2C9. Demographic data, warfarin dose per week, prothrombin time (INR), indications and co-morbid diseases were assessed for each group. Total 90 patients on warfarin were evaluated; The low dose group has taken warfarin 7.6$\pm$1.7 mg/week, which was significantly lower than 31.4$\pm$0.9 mg/week in the regular dose group (p<0.0001). The measured INR in the low dose group was similar to that of the regular dose group (2.3$\pm$0.7 vs. 2.3$\pm$0.6, p=0.9). Even though there was a higher possibility of CYP2C9 variation in the low dose group, no polymorphism in CYP2C9 was detected. All patients were homozygous C416 in exon 3 for CYP2C9*2 and A1061 in exon 7 for CYP2C9*3. The DNA sequencing data confirmed the homozygous C416 and A 1061 alleles. In conclusion, polymorphism in CYP2C9 is not a critical factor for assessing warfarin dose requirement and risk of bleeding complications in a Korean population.

• Toxicological Research
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• 제23권4호
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• pp.353-362
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• 2007

Deoxynivalenol (DON) is a common food borne mycotoxin and occurs predominantly in grains such as wheat, barley, oats, etc. DON induces systemic health problems such as loss of appetite, emesis and diarrhea in both human and farm animals. Reliable diagnostic parameters for DON intoxication are needed to prevent deep health impact. In order to establish useful diagnostic parameters, we investigated clinical signs, hematological values, serum biochemical values, gross-, histo- and toxico-pathological findings in B6C3F1 male mice after oral administration of DON (0.83, 2.5 and 7.5 mg/kg) for 8 days. Body weight gain was significantly decreased at the highest dose of DON. Anorexia, ataxia, for crudness and lack of vigor were observed at the highest dose DON group. In hematological values, the numbers of WBC and platelets and hemoglobin content were reduced with decreased neutrophil and monocytes by 7.5 mg/kg DON. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged in a dose-dependent manner and the content of fibrinogen was elevated at high dose of DON. Of serum biochemical values, total protein, globulin, BUN, cholesterol and test-osterone were reduced but total bilirubin and albumin/globulin ratio increased. The enzyme activity of alkaline phosphatase was decreased while that of alanine aminotransferase was elevated. Relative organ weights of thymus, seminal vesicle/prostate and testes were dose-dependently reduced but those of liver and left adrenal gland increased with dose dependency. As for pathological findings, atrophy of thymus, seminal vesicle/prostate and testes and submucosal edema and ulceration in stomach and depletion of lymphocytes in thymus cortex were observed. In conclusion, these clinical, hematological, blood biochemical and patholgical parameters obtained in the present studies can be used for diagnosis of DON-mycotoxicosis, especially, low WBC, platelets, protein, BUN and testosterone and delayed prothrombin time can be available as for reliable diagnostic parameters.

• 동의생리병리학회지
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• 제21권3호
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• pp.671-678
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• 2007

Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Gamigukihwandong-hwan has been known to be effective for the treatment of diabetes. The present study was carried out to investigate the effect of Gamigukihwandong-hwan on renal function, peroxynitrite (ONOO$^-$) scavenging activity and polyol pathway in streptozotocin-induced diabetic rats. The crushed Gamigukihwandong-hwan was extracted 3 times, each time with 3 volumes of methyl alcohol at 60$^{\circ}C$ for 24 h. The extract was filtered and evaporated under a reduced pressure using a rotary evaporator to yield 74.95 g. Gamigukihwandong-hwan extract was oral-administered 100 mg per 1 kg of body weight for 20 days to the diabetic rats induced by streptozotocin (60 mg/kg). The effects of Gamigukihwandong-hwan extract on the streptozotocin-induced diabetic rats were observed by measuring the serum level of glucose, insulin, lipid components, creatinine and BUN, and also the kidney levels of superoxide anion radical (${\cdot}O_2^-$), nitric oxide (NO) and ONOO$^-$, and also the enzyme activities involved in polyol pathway. The Effects of Gamigukihwandong-hwan on the streptozotocin-induced diabetic rats with regards to body weight, blood glucose and insulin levels, creatinine and BUN levels, total cholesterol and triglyceride levels, and HDL-cholesterol levels were all shown to be good enough to cure and prevent the diabetes and its complications. Gamigukihwandong-hwan inhibited the generation of ${\cdot}O_2^-$, NO and ONOO$^-$ in the kidney of streptozotocin-induced diabetic rats. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the streptozotocin-induced diabetic rats, whereas the ones in the Gamigukihwandong-hwan administered group among the streptozotocin-induced diabetic rats were reversed toward the natural activities. Gamigukihwandong-hwan might inhibit the development of diabetic nephropathy by scavenging reactive oxygen and nitrogen species, thereby by reducing oxidative stresses and also by regulating the activities of polyol pathway enzymes, all of which could help to recover the function of kidney.