• Korean Journal of Plant Resources
• /
• v.30 no.2
• /
• pp.240-264
• /
• 2017

The present study was carried out to identify traditional konwledges on Korean Campanulaceae plants and conduct a comprehensive review of them through analyzing phytochemistry and pharmacology of Korean Campanulaceae plants. According to the literature study, the ethnobotanical plants of Korean Campanulacae consisted of a total 18 taxa. Of them, 12 taxa including Platycodon grandiflorus, Adenophora triphylla var. japonica, Codonopsis lanceolata and others have been used as ethnomedicinal plants. These plants have been used for the treatment of 49 diseases such as cold, asthma and postnatal care. Phytochemical studies have identified the constituents present from Korean Campanulaceae (Adenophora, Codonopsis, Platycodon, Campanula and Asyneuma). A wide range of chemical compounds comprised 109 triterpenes, 8 sterols, 4 polyacetylenes, 21 alkaloids, 14 flavonoids, 14 phenolic acids, 11 phenolic glycosides, 8 phenylpropanoids and 22 other compounds. Pharmacological studies of these compounds have demonstrated immuno-stimulating, anti-inflammatory, anti-asthmatic, apophlegmatic and anti-allergic effects. They have also shown antioxidant, estrogenic, anti-diabetic, hepatoprotective, neuroprotective, antinociception and anti-tumor activities, as well as anti-obesity and cardiovascular effects. In light of traditional knowledge and phytochemical and pharmacological studies summarized, uses of Korean Campanulaceae based on traditional knowledge (for the treatment diseases and conditions of respiratory, pregnancy, childbirth, puerperium, genitourinary, circulatory, musculoskeletal and other systems) have been supported by phytochemical and pharmacological studies.

• Environmental Mutagens and Carcinogens
• /
• v.23 no.3
• /
• pp.94-98
• /
• 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
• /
• v.36 no.6
• /
• pp.603-612
• /
• 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.

• Development and Reproduction
• /
• v.4 no.1
• /
• pp.53-59
• /
• 2000

Endocrine disruptors (EDs) are exogenous chemicals which interfere several aspects of natural hormone properties. EDs with estrogenic activity have been recently reported to cause animal reproductive problems. This study was performed to investigate the effects of bisphenol A (BPA) on the mouse spermatogenesis in vivo. Male ICR mice were orally injected on a daily basis with low dose of BPA 20 mg/kg, high dose of BPA 200 mg/kg, or corn oil (vehicle control) for 7 days, and litter size and weights of body, testis, and cauda epididymis were measured. The level of serum testosterone and the expression of TGF- $\beta$$_1$ mRNA were also analyzed using RIA and RT-PCR, respectively. Also, morphological differences of testes after treatments were examined. Sperm concentration and level of serum testosterone showed a decreasing tendency detected as untreated >corn oil >low >high dose BPA treated mice, although there were no significant statistical differences. Interestingly, in mice treated with a high dose of BPA, partial disappearance of spermatozoa in seminiferous tubular lumen and the expression of TGF-$\beta$$_1$ mRNA were observed. Spermatogenesis was disrupted through TGF-$\beta$ system in the seminiferous tubules, resulting in no development of germ cells. Similarly, the litter size treated with a high dose of BPA was significantly different from that of untreated control group. In conclusion, these results that a high dose of BPA (200 mg/kg) acts as an endocrine disruptor during apermatogenesis in male mice md that there are BPA-specific lesions in the adult male reproductive tract might represent a permanently altered responsiveness to testosterone by BPA in the affected target tissue.

• Korean Journal of Ichthyology
• /
• v.12 no.3
• /
• pp.180-185
• /
• 2000

The effects of bisphenol-A(BPA), a monomer of plastics used in many consumer products, on vitellogenin(VTG) synthesis were examined in primary hepatocyte culture of olive flounder, Paralichthys olivaceus. The hepatocytes were precultured for 2 days, and then estradiol-$17\beta(10^{-6}M)$ and BPA were simultaneously added to the incubation medium. The hepatocytes were cultured for 6 more days and then spent medium was analyzed by SDS-PAGE. BPA increased the rate of VTG to total protein concentrations in a concentration-dependent way, and a significant difference was obtained at concentrations of $10^{-6}M$ and $10^{-5}M$ (P<0.05). In particular, the rate of VTG to total protein concentrations was 26.36% at $10^{-5}M$ of BPA, and its level did not differ from the control level with $E_2$ alone. $E_2$ and/or BPA-primed VTG synthesis was markedly inhibited to about 80% of the control(with $E_2$) by the addition of tamoxifen($10^{-6}M$) to the incubation medium. Furthermore, In vivo $E_2$-primed VTG synthesis was significantly inhibited by in vitro $E_2$-free incubation of hepatocyte to about 22% of the control (with $E_2$) on Day 6. The effect of reducing was delayed in a BPA concentration-dependent way. These results suggest that BPA induce VTG synthesis by estrogenic activity through estrogen receptor mediated response and prolong VTG synthesis on vitellogenesis in olive flounder.

• Development and Reproduction
• /
• v.21 no.2
• /
• pp.121-130
• /
• 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.

• Proceedings of the Korean Society of Embryo Transfer Conference
• /
• 2002.11a
• /
• pp.109-109
• /
• 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.

• Biomedical Science Letters
• /
• v.11 no.2
• /
• pp.175-183
• /
• 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.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.32 no.7
• /
• pp.1114-1119
• /
• 2003

The aim of this study was to evaluate the effects of Sedum sarmentosum Bunge (SS) on the collagen content of the connective tissues in ovariectomized rats. From day 2 until day 37 after the ovariectomy, Sprague-Dawley female rats were randomly assigned to the following groups: sham-operated rats (Sham), ovariectomized control rats (OVX-control), ovariectomized rats supplemented with SS at 50 mg/kg BW/day (OVX-SS50), 100 mg/kg bw/day (OVX-SS100) and 200 mg/kg bw/day (OVX-SS200), and an ethyl ether fraction of SS at 10 mg/kg bw/day (OVX-EE) and an ethyl acetate fraction of SS at 10 mg/kg bw/day (OVX-EA). The SS ethanol extracts and SS fractions were orally administrated 1 mL per day. The OVX rats were significantly heavier than the sham-operated rats at all time points, but supplementation with the SS extracts tended to gain weight less than OVX-control. Supplementation with the SS extracts prevented a decrease in the collagen level in bone and cartilage tissues. These results are consistent with the conclusions based on the estrogenic activities of SS. Therefore, it may be used to possibly improve the quality of life in menopausal women.

• Development and Reproduction
• /
• v.10 no.3
• /
• pp.177-184
• /
• 2006

Retinol-binding protein(RBP) plays an important role in the specific transport of retinol to target cells through the blood stream in higher vertebrates. In order to clarify the effects of 4-nonylphenol(4-NP) on RBP mRNA expression in the rockfish, Sebastes schlegeli which is common in coastal waters of Korea and commercially important species, the cDNA library was constructed from the liver, and a partial fragment of the RBP gene was cloned. The deduced amino acid sequence from the RBP mRNA showed a high homology to the amino acid sequence from Sparus aurata(80%), Oncorhynchus mykiss(72%) or Anguilla anguilla(78%). Effects of 4-NP on RBP and vitellogenin(VTG) mRNA expression level in rockfish were examined by the northern blot analysis. In female and male rockfish injected with 4-NP(10 mg/kg BW, lower dose), there was no changes in the levels of VTG mRNA expression in the liver. The RBP mRNA levels, however, decreased at 48 hours after the injection in male. In the rockfish injected with 4-NP(25 mg/kg BW, higher dose), the level of VTG mRNA expression increased after 24 hours, regardless of sex. The level of RBP mRNA expression decreased at 48 hours after the injection in both sexes. These data indicate that estrogenic mimics such as 4-NP exhibit a contrasting effect on RBP and VTG gene expression in rockfish.