• 한국자원식물학회지
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• 제30권2호
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• pp.240-264
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• 2017

한국산 초롱꽃과 식물의 전통지식을 확인하고, 이들의 화학성분, 약리효과에 관한 자료와의 비교 분석을 통해 종합적인 고찰을 수행하였다. 그 결과, 민속식물은 총 18분류군으로 식용, 약용, 관상용 등으로 이용되고 있으며, 이 중 약용으로는 도라지, 잔대, 더덕 등 총 12분류군이 확인되었다. 약용 전통지식은 감기, 천식, 산후조리 등 49개의 질병 및 질환을 치료하기 위해 이용된 것으로 조사되었다. 지금까지 한국산 초롱꽃과 잔대속, 더덕속, 도라지속, 초롱꽃속, 영아자속에서 총 211개의 화학성분이 선행 연구자들에 의해 밝혀졌으며, 이들은 triterpenes 109종류, sterols 8종류, polyacetylens 4종류, alkaloids 21종류, flavonoids 14종류, phenolic acids 14종류, phenolic glycosides 11종류, phenylpropanoids 8종류, 그 밖의 성분으로 organic acid 계열 등 22종류이다. 약리효과로는 면역활성, 항염증, 항천식 및 점액분비촉진, 항알레르기, 항산화, 에스트로겐 활성, 항당뇨, 간 보호, 신경 보호, 항종양, 항진통, 순환계, 항비만 등에 효과가 있는 것으로 조사되었다. 조사된 전통지식과 화학성분, 약리효과에 대한 자료를 종합해 본 결과, 한국산 초롱꽃과 식물을 호흡기 계통, 임신 출산 산후조리, 생식 배설 계통, 순환 계통, 근골격계 계통 등의 질병 및 질환에 사용된 전통지식은 해당 식물체 조추출물 및 화학성분을 이용한 약리 실험을 통해 그 효과가 입증되었다고 판단된다.

• 한국환경성돌연변이발암원학회지
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• 제23권3호
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• pp.94-98
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• 2003

Quercetin and naringenin are representative flavonoids that not only exert anti estrogenic, cholesterol-lowering and antioxidant activities but also can modulate the metabolism of many xenobiotics. The activity of the specific form(s) of CYP450 is likely to be a major determinant of susceptibility to chemically induced carcinogenesis between which varies among between individuals due to different dietary habits as well as genetic characteristics. People consume cooked meat or fish together with various vegetables containing substantial amounts of quercetin and naringenin that can modify the enzyme activity of CYP1A2 to stimulate or to inhibit the mutagenic activities of HCAs. Heterocyclic amines (HCAs) produced by cooking meat products at high temperatures are promutagens that are activated by cytochrome P450 (CYP) lA2. Using a newly developed Salmonella typhimurium TA1538/1A2bc-b5 strain, we tested the effect of quercetin and naringenin on the mutagenicity of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). TA1538/1A2bc-b5 bears two plasmids, one expressing human CYP1A2 and NADPH-P450 reductase (NPR), and the other plasmid which expresses human cytochrome b5 (cyp b5). TA1538/1A2bc-b5 cells showed high activities of 7-ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) associated with CYP1A2 and are very sensitive to mutagenesis induced by several HCAs. MeIQ was found to be the strongest mutagen among the HCAs tested in this system. Mutagenicity of MeIQ was enhanced 50 and 42% by quercetin at 0.1 and 1 mM, respectively, but suppressed 82% and 96% at 50 mM and 100 mM. Naringenin also increased the MeIQ-induced mutation about 37% and 22% at 0.1 and 1 mM, but suppressed it 32% and 63% at 50 mM and 100 mM concentrations, respectively, in TA 1538/1A2bc-b5 cells. Thus, they stimulated the MeIQ induced mutation at low concentrations, but strongly suppressed it at high concentrations. This biphasic effect of flavonoids was due to the stimulation or the inhibition of CYP1A2 activity in a dose-dependent manner judging by the activities of EROD or MROD in the Salmonella cells. Collectively, it is likely that the biphasic effects of quercetin and naringenin on the MeIQ-induced mutagenesis in S. typhimurium TA1538/CYP1A2bc-b5 were due to their differential modification of the CYP1A2 activity in these cells.

• Journal of Nutrition and Health
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• 제36권6호
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• pp.603-612
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• 2003

Postmenopausal women are at an increased risk of developing coronary artery disease. This is due to primarily dyslipidemia accompanying the loss of estrogen secretion. Soy isoflavones are known to have weak estrogenic effects. The purpose of this study is to investigate whether isoflavone supplement improves the risk of cardiovascular disease in hypercholesterolemic postmenopausal women. Subjects consisted of 39 Korean postmenopausal women with hypercholesterolemia (total cholesterol $\geq$ 200 mg/㎗ or LDL cholesterol $\geq$ 130 mg/㎗). Subjects were divided into 2 groups; placebo group (PG), isoflavone supplement group (IG). During 12 weeks, subjects were given placebo and 80mg isoflavone daily. Anthropometric measurement, blood sample analysis and dietary intake measurement were taken at baseline and after 12 weeks. After 12 weeks, systolic blood pressure was decreased significantly (p ＜ 0.01) and plasma HDL cholesterol level was increased significantly (p ＜ 0.05) in IG. But there were no significant changes in plasma total cholesterol, LDL cholesterol and triglyceride levels after isoflavone supplementation. There was a negative correlation between initial plasma HDL cholesterol level and the extent of plasma HDL cholesterol reduction in IG (r＝-0.572, p＝0.012). Atherogenic index (AI), total-/LDL- cholesterol ratio and LDL/HDL cholesterol ratio were improved significantly after isoflavone supplementation. In subjects whose initial plasma LDL cholesterol level were above 160 mg/㎗, plasma malondialdehyde (MDA) level were decreased and total antioxidant status (TAS) were increased significantly after isoflavone supplement (p ＜ 0.05). However there were no significant changes in flow-mediated dilator (FMD), the marker of endothelium-dependent vasodilation and nitroglycerine-mediated dilator (NMD), the marker of endothelium-independent vasodilation and the extent of DNA damage after isoflavone supplement. In conclusion, these results indicate that isoflavone supplement may decrease the risk of cardiovascular disease via improving blood pressure, HDL cholesterol level and AI in hypercholesterolemic postmenopausal women. Futhermore, in case of subjects with elevated LDL cholesterol level, isoflavone supplementation may have more antiatherogenic effects via improving antioxidant status.

• 한국발생생물학회지:발생과생식
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• 제4권1호
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• pp.53-59
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• 2000

내분비계 장애물질은 생체내에서 호르몬 등의 내분비계에 영향을 주기 때문에 미량으로도 생식기능에 이상을 가져 올 수 있고, 급ㆍ만성 독성과는 달리 차세대에 그 영향이 발현될 수 있다. 대부분의 내분비계 장애물질은 에스트로겐 유사물질로 알려져 있으며, 내분비계 장애물질의 하나인 bisphenol A (BPA)도 이러한 성질을 가진 물질이다. 본 연구는 BPA가 생쥐의 정자형성과정에 어떤 영향을 미치는가를 분석하고자, 농도별 (저농도, 20 mg/kg, 고농도 200 mg/kg) 구강투여를 실시하였다. 정자수와 테스토스테론 농도 및 산자수가 대조군에 비해 처리군에서 점진적으로 감소하는 경향을 보였으며, 산자수에서 유의적인 차이(P<0.01)를 나타내었다. 특히 국부적이긴 하지만 세정관 내강에서의 정자세포 소실 양상은 정자수의 감소 원인으로 사료된다. 성성숙 이후 정소에서의 발현이 소실되는 것으로 알려진 TGF-$\beta$계에서는 TGF-$\beta$1이 고농도의 BPA투여시 발현되었지만, 그 외의 리간드와 수용체의 발현은 관찰되지 못했다. 결론적으로 고농도의 BPA노출은 웅성생식계에 영향을 미칠 수 있으며, 이는 정자형성에 장애를 일으켜 불임을 유발할 수도 있을 것으로 보여진다.

• 한국어류학회지
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• 제12권3호
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• pp.180-185
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• 2000

플라스틱의 원재료로 이용되는 bisphenol-A (BPA)가 vitellogenin (VTG)의 합성에 미치는 영향을 넙치의 간세포를 초대 배양하여 조사하였다. 간세포는 2일간 사전 배양을 하였으며, estradiol-$17\beta(E_2)$ 및 BPA를 배양액에 동시 첨가하였다. 간세포는 6일간 배양한 후 배양액을 회수하여 SDS-PAGE로 분석하였다. BPA는 농도 의존적으로 총 단백질에 대한 VTG 비율은 증가하였으며, $10^{-6}M$과 $10^{-5}M$의 농도에서 유의한 차이를 나타내었다(P<0.05). 특히, BPA $10^{-5}M$의 농도에서의 총 단백질에 대한 VTG 비율은 26.36%로 $E_2$만을 첨가한 대조군과 유의한 차이를 나타내지 않았다. $E_2$와 BPA를 단독 또는 동시에 첨가하여 유도된 VTG합성은 배양액에 tamoxifen$(10^{-6}M)$을 첨가함으로서 $E_2$를 첨가한 대조군의 약 80%로 유의하게 억제되었다. 그리고, in vivo에서 $E_2$에 의해 유도된 VTG합성은 in vitro에서 간세포를 6일간 배양함에 따라 $E_2$를 첨가한 대조군의 약 22%까지 억제되었다. 이러한 감소효과는 BPA의 농도 의존적으로 지연되는 결과를 나타내었다. 따라서 넙치에서의 BPA는 $E_2$ receptor와의 반응을 통한 에스트로겐 작용에 의해 VTG합성을 유도하고, 난황형성기에서의 VTG 합성을 장시간 지속시킬 가능성이 있는 것으로 추측된다.

• 한국발생생물학회지:발생과생식
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• 제21권2호
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• pp.121-130
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• 2017

4-Nonylphenol (NP) is a surfactant that is a well-known and widespread estrogenic endocrine disrupting chemical (EDC). Although it has been known that the affinity of NP to ERs is low, it has been suggested that low-dose NP has toxicity. In the present study, the endocrine disrupting effects on reproduction, and the weight of gonads, epididymis, and uterus were evaluated with the chronic lower-dose NP exposing. This study was designed by following the OECD test guideline 443 and subjected to a complete necropsy. In male, NP had an effect on the weight of the testis and epididymis in both $F_0$ and $F_1$. In females, NP decreased the weight of ovary and uterus in $F_0$ but not in pre-pubertal $F_1$ pubs. Fertility of male and female in $F_0$ or $F_1$ was no related with NP administration. The number of caudal-epididymal sperm by body weight (BW) was not different between groups in both $F_0$ and $F_1$. Besides, the difference of the sperm number between generations was not detected. The number of ovulated oocytes was similar between groups in $F_0$, but significantly decreased in NP 50 group of $F_1$. The litter size and sex ratios of offspring in $F_1$ and $F_2$ were not different. The accumulated mating rate and gestation period were not affected by the NP administration. Those results shows that chronic lower-dose NP administration has an effect of endocrine disruptor on the weight of gonads and epididymis of $F_0$ and $F_1$ but not in reproduction. Based on the results, it is suggested that chronic lower-dose NP exposing causes endocrine disruption in the weight of gonad and epididymis but not in the reproductive ability of next generations.

• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2002년도 국제심포지엄
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• pp.109-109
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• 2002

In recent reports, the multiple reproductive defects such as cryptorchidism, hypospadias, epididymal cysts, low sperm counts, and testicular cancers are increased in humans, and these changes were doubted by the chemicals with estrogenic or antiandrogenic activities in our environment. To compare the effects of neonatal exposure of di (n-butyl) phthalate and flutamide on the development of reproductive organs and to identify the specific mechanisms of these abnormalities related to the male reproducton, Sprague-Dawley neonate male rats were injected subcutaneously during 5-14 days after birth with corn oil (control), flutamide (0.05, 0.1, and 0.5 mg/animal) and DBP (5, 10, and 20 mg/animal). Animals were killed at 31 (immature) and 42 (pubertal) days of age respectively and blood was collected from abdominal aorta for serum testosterone analysis. Testes, epididymides, seminal vesicles, ventral prostate, levator ani plus bulbocavernosus muscle (LABC), cowpers glands and glans penis were weighed. Expression of steroid hormone receptors (AR and ER) was examined in the testes and ventral prostate. At 31 days of age, ventral prostate, seminal vesicles, LABC, and cowpers glands significantly decreased in the flutamide (0.5 mg/animal) and DBP (20 mg/animal), but serum testosterone levels were not changed. Flutamide slightly delayed the testes descent at the high dose (0.5 mg/animal), but DBP did not show any significant effect on the testes descent at all doses. DBP and flutamide decreased the expression of AR protein in the testes but did not affect the expression of ERa and ER protein in the testes. At 42 days of age, ventral prostate, seminal vesicles, and cowpers glands weights were still significantly decreased at the high dose of flutamide (0.5 mg/animal) and DBP (20 mg/animal), but the weights of testes and epididymides were not different. Serum testosterone decreased significantly in DBP treated animals and slightly, not significantly, in flutamide group. While DBP still significantly decreased the expression of AR protein in testis, flutamide recovered from downregulation of AR protein and did not affect the expression of ERa and ER protein in the testes. Based on these results, flutamide and DBP have shown several similar patterns in reproductive abnormalitis, but some marked differences which may be caused by different acting mechanism.

• 대한의생명과학회지
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• 제11권2호
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• pp.175-183
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• 2005

The two major isoflavones in soy, genistein and daidzein, are well known to prevent hormone-dependent cancers by their anti estrogenic activity. The exact molecular mechanisms for the protective action are, however, not provided yet. It has been reported that genistein and daidzein have a potential anticancer activity through their antiproliferative effect in many hormone-dependent cancer cell lines. Transforming growth $factor-\beta1(TGF-\beta1)$ has also been found to have cell growth inhibitory effect, especially in mammary epithelial cells. This knowledge led to a hypothetical mechanism that the soy isoflavones-induced growth inhibitory effect can be derived from the regulation of $TGF-\beta1$ and $TGF-\beta$ receptors. In order to test this hypothesis, the effects of the soy isoflavones at various concentrations and periods on the expression of $TGF-\beta1$and $TGF-\beta$ receptors were investigated by using Northern blot analysis in human breast carcinoma epithelial cell lines, an estrogen receptor positive cell line (MCF-7) and an estrogen receptor negative cell line (MDA-MB-231). As a result, only genistein has shown a profound dose-dependent effect on $TGF-\beta1$ expression in the $ER^+$ cell line within the range of doses tested, and the expression levels are correspondent to their inhibitory activities of cell growth. Moreover, daidzein showed down-regulated $TGF-\beta1$ expression at a low dose, the cell growth proliferation was promoted at the same condition. Therefore, antiproliferative activity of the soy isoflavones can be mediated by $TGF-\beta1$ expression, and the effects are mainly, if not all, occurred by ER dependent pathway. The expression of $TGF-\beta$ receptors was induced at a lower dose than the one for $TGF-{\beta}1$ induction regardless of the presence of ER, and the expression patterns are similar to those of the cell growth inhibition. These results indicated that the regulation of $TGF-\beta$ receptor expression as well, prior to $TGF-\beta1$ expression, may be involved in the antiproliferative activity of soy isoflavones. Little or no expression of $TGF-\beta$ receptors was found in the MCF-7 and MDA-MB-231 cells, suggesting refractory properties of the cells to growth inhibitory effect of the $TGF-\beta$. The soy isoflavones can seemingly restore the sensitivity of growth inhibitory responses to $TGF-\beta1$ by re-inducing $TGF-\beta$ receptors expression. In conclusions, our findings presented in this study show that the antitumorigenic activity of the soy isoflavones could be mediated by not only $TGF-\beta1$induction but $TGF-\beta$ receptor restoration. Thus, soy isoflavones could be good model molecules to develop new nonsteroidal antiestrogenic chemopreventive agents, associated with, regulation of $TGF-\beta$ and its receptors.

• 한국식품영양과학회지
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• 제32권7호
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• pp.1114-1119
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• 2003

폐경을 앞둔 여성에게는 폐경을 전후하여 지속되는 골 손실 가속화 등의 문제점을 가지고 있다. 그러므로 본 연구에서는 인위적 폐경을 유발시킬 수 있는 난소 절제 쥐에서의 골 손실의 유무를 결합조직 중의 collagen함량 변화를 통하여 그 효과를 검토하였다. 난소 절제 후 결합조직 중의 Collagen 함량은 난소를 절제하지 않은 Sham군에 비해 낮았으나 돌나물 추출물 투여에 의해 투여하지 않은 군보다 전체적으로 높게 나타났다. 난소 절제시 나타나는 결합조직 중 collagen 함량 저하에 대하여 돌나물 추출물의 작용 가능성이 밝혀졌으므로, 돌나물을 분획하여 그 효능을 검증하였다. 그 결과 생화학적 골 대사 지표인 혈 중 ALP 활성은 난소 절제로 (OVX-control)로 인하여 증가하는 반면, 난소 절제 후 돌나물 분획 투여 (OVX-EE, OVX-EA)로 혈 중 ALP 활성은 감소하는 경향을 보여 골 흡수를 저하시킬 수 있는 가능성을 나타내었다. 한편 난소 절제 후 돌나물 분획물 투여에 의해 폐 조직과 골$.$연골 조직에서 collagen 함량이 증가하는 경향을 보였고, 그 중 연골 조직에서는 collagen 함량의 저하가 정상적으로 회복되었다. 한편 피부 조직에서도 난소 절제 후 돌나물 분획물 투여군 모두에서 collagen 합성량이 유의적으로 증가하였다. 돌나물 추출물과 분획물이 에스트로겐 감소로 인한 Collagen 합성저하를 회복시킨 본 실험 결과로 미루어 보아 돌나물 중의 phytoestrogen이 에스트로겐 유사효과를 나타냄을 알 수 있었고, 외인성 에스트로겐 투여로 인한 부작용을 줄여 줄 수 있을 것으로 기대된다. 이상과 같이 폐경기 여성에게 돌나물의 섭취는 폐경으로 인한 장애를 감소시키기 위하여 에스트로겐의 장기간 복용에 의한 부작용을 돌나물 중의 phytoestrogen이 estrogen 대체 작용을 함으로써 그 부작용을 감소시켜 줄 것으로 사료되며, 이들의 구조 및 기전에 대해서는 앞으로 연구가 더 필요한 것으로 생각된다.

• 한국발생생물학회지:발생과생식
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• 제10권3호
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• pp.177-184
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• 2006

레티놀 결합 단백질(retinol-binding protein, RBP)은 고등 척추동물에서 혈류를 통해 특이적으로 레티놀을 표적세포에 운반해 주는 중요한 역할을 한다. 우리나라의 연안에 서식하고 있으며 산업적으로 중요한 조피볼락(Sebastes schlegeli)을 대상으로 4-nonylphenol(NP)가 RBP mRNA 발현에 미치는 영향을 구명하기 위해 간으로부터 cDNA library를 제작하고 RBP 단편의 염기서열을 분석하였다. 분석된 RBP mRNA 서열로부터 아미노산 서열을 추정하여 다른 종의 RBP 아미노산 서열과 비교한 결과 Sparus aurata와는 80%, 무지개 송어(Oncorhynchus mykiss)와는 72%, 유럽 뱀장어(Anguilla anguilla)와는 78%의 높은 상동성을 보였다. 조피볼락에서 4-NP에 대한 RBP와 VTG mRNAs 발현에 미치는 영향을 northern blot 분석 방법에 의해 조사하였다. 4-NP를 10 mg/kg BW로 주사한 실험구에서는 암수 모두 VTG mRNA 발현에 영향을 주지 않았으나, RBP mRNA 발현은 수컷에서 48시간 후에 감소하였다. 4-NP를 25 mg/kg BW으로 주사한 실험구에서는 24시간 후에 암수 모두 VTG mRNA 발현이 증가하였으며, RBP mRNA 발현은 48시간 후에 암수 모두 감소하였다. 이들 결과로부터 조피볼락에서는 4-NP 등의 에스트로겐 유사물질이 RBP와 VTG 유전자 발현에 상반되는 효과를 유도함을 알 수 있었다.