Alcohol-induced fatty liver (steatosis) results from excessive generation of reducing equivalents by ethanol metabolism. Generally, chronic ethanol treatment causes hepatosteatosis by regulating sterol regulatory element-binding protein 1c (SREBP-1c), which increases the synthesis of hepatic lipids. The effect of ethanol on SREBP-1c is mediated through mammalian sirtuin-1 (SIRT-1), a NAD+-dependent protein deacetylase that regulates hepatic lipid metabolism. Ginseng is a widely used herbal medicine that is used in Asia for its anti-diabetes and anti-obesity effects. The pharmacological and therapeutic effects of ginseng are primarily produced by bioactive constituents known as ginsenosides. Here, we examined the regulatory effects of Korean red ginseng (KRG) extracts on SREBP-1c and SIRT-1 on lipid homeostasis in AML-12 mouse hepatocytes. AML-12 cells were treated with ethanol and/or KRG extracts (0 - 1,000 μg/ml). Lipid droplets were assayed using Oil red O staining, and western blotting was used to measure SIRT-1 and SREBP-1 expression. Treatment with KRG extracts restored SIRT-1 expression and reduced SREBP-1c expression in ethanol-treated cells. We also showed that KRG extract and ginsenosides Rb2 and Rd significantly decreased SREBP-1 acetylation in ethanol-treated cells. These results show that treatment with KRG extract and its active ginsenoside constituents Rb2 and Rd protected against alcohol-related hepatosteatosis via regulation of SIRT-1 and downstream acetylation of SREBP-1c, which altered hepatic lipid metabolism.
$C/EBP{\beta}$ and $C/EBP{\delta}$ are required for the initiation of adipogenesis and induce the expression of key adipogenic regulators, such as $PPAR{\gamma}$ and $C/EBP{\alpha}$. In the present study, we have examined the effects of silibinin and its possible molecular mechanisms in regulating adipocyte differentiation and expression of $C/EBP{\beta}$ and $C/EBP{\delta}$ in the early stage of adipogenesis. Silibinin statistically significantly inhibits intracellular lipid accumulation and the mRNA expression of various genes involved at different stages during adipogenesis. Silibinin also suppresses expression of lipoprotein lipase (LPL), fatty acid binding protein 4 (AP2), and adiponectin in 3T3-L1 adipocytes. Thus, the anti-adipogenic effect of silibinin seems to originate from the ability to inhibit the expression of $C/EBP{\beta}$ and $C/EBP{\delta}$. Furthermore, silibinin decreases cell viability for differentiation period and induces apoptotic cell death through capspase-3 activation.
In our previous study, it was reported that an herbal mixture, SH21B, inhibits fat accumulation and adipogenesis both in vitro and in vivo models of obesity. SH21B is a mixture composed of seven herbs: Scutellaria baicalensis Georgi, Prunus armeniaca Maxim, Ephedra sinica Stapf, Acorus gramineus Soland, Typha orientalis Presl, Polygala tenuifolia Willd, and Nelumbo nucifera Gaertner (Ratio 3:3:3:3:3:2:2). The aim of this study was to investigate the detailed molecular mechanisms of the effects of SH21B on various regulators of the adipogenesis pathway. During the adipogenesis of 3T3-L1 cells, SH21B significantly decreased the expression levels of central transcription factors of adipogenesis, such as peroxisome proliferator-activated receptor (PPAR)$\gamma$ and CCAAT/enhancer binding protein (C/EBP)$\alpha$. To elucidate the detailed molecular mechanism of the anti-adipogenic effects of SH21B, we examined the expression levels of the various pro-adipogenic or anti-adipogenic regulators of adipogenesis upstream of $PPAR{\gamma}$ and C/$EBP{\alpha}$. The mRNA levels of Krox20 and Kruppel-like factor (KLF) 15, which are pro-adipogenic regulators, were significantly down-regulated by SH21B treatment, whereas the mRNA levels of C/$EBP{\gamma}$ and KLF5 were not changed. KLF2 and C/EBP homologous protein (CHOP), which are anti-adipogenic regulators, were significantly up-regulated by SH21B treatment. These results suggest that the molecular mechanism of the anti-adipogenic effect of SH21B involves both the down-regulations of pro-adipogenic regulators, such as Krox20 and KLF15, and the up-regulations of anti-adipogenic regulators, such as KLF2 and CHOP, which results in the suppression of central transcription factors of adipogenesis including $PPAR{\gamma}$ and C/$EBP{\alpha}$.
Kim, Dong-Gyu;Kang, Min Jung;Suh, Hwa Jin;Kwon, Oh Oun;Shin, Jung Hye
Journal of the Korean Society of Food Science and Nutrition
/
v.45
no.8
/
pp.1107-1113
/
2016
The purpose of this study was to investigate the effects of catechu water extract on adipogenesis in 3T3-L1 adipocytes. 3T3-L1 preadipocytes were differentiated with adipogenic regents by incubation for 9 days in the absence or presence of catechu extract ranging from $1{\sim}200{\mu}g/mL$. The effect of catechu extracts on cell proliferation of 3T3-L1 preadipocytes was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of catechu extracts on 3T3-L1 differentiation was examined by measuring intracellular lipid droplet and triglyceride contents. These results were obtained from preadipocyte proliferation and adipocyte differentiation of 3T3-L1. Catechu extracts inhibited lipid accumulation and remarkably decreased triglyceride contents in 3T3-L1 preadipocytes at a concentration showing no cytotoxicity. The anti-adipogenic effects of catechu appeared to be mediated by significant down-regulation of expression of peroxisome proliferator-activated receptor ${\gamma}$, CCAAT/enhancer-binding protein ${\alpha}$, and sterol regulatory element-binding protein 1c proteins apart from expression of hormone-sensitive lipase. We suggest that catechu extracts significantly inhibit adipogenesis and can be used for regulation of obesity.
Min, Ki Sung;Han, Daeseok;Kwon, Sang-Oh;Yeo, Kyung-Mok;Kim, Bok-Nam;Ly, Sun Yung
Journal of Nutrition and Health
/
v.47
no.1
/
pp.23-32
/
2014
Purpose: This study was conducted in order to investigate the effect of Sargassum confusum extracts on the reduction of body fat for eight weeks in overweight women ($BMI{\geq_-}23kg/m^2$). Methods: Subjects were classified by double-blind randomized trial as the control group (C group, n = 14) and the Sargassum confusum extract supplementation group (SC group, n = 16), which consumed 12 tablets per day. Questionnaires related to their health status were assessed twice (week 0 and week 8). Their dietary intake status was evaluated by 24-recall method and body compositions were measured using a bioelectrical impedance analyzer. In addition, we assessed the anti-obesity effect and the occurrence possibility of health risk factors during the supplementation periods by hematological and clinical analysis of blood. Results: Waist circumference and body fat (%) were significantly decreased in the SC group. Serum leptin level was also significantly decreased in the SC group. Defecation frequency was significantly increased in the SC group. The above results indicate that Sargassum confusum extract supplementation improves overweight on visceral fat and blood leptin level by increasing bowel movement. These results imply a decrease of health risk factors in overweight women. Seven subjects withdrew from the study due to adverse events; however, no differences regarding adverse events were observed between the control and treatment group. Conclusion: Therefore, Sargassum confusum extract is a plausible effective agent for body fat reduction in humans.
Benrahou, Kaoutar;El Guourrami, Otman;Mrabti, Hanae Naceiri;Cherrah, Yahia;My El Abbes, Faouzi
Journal of Pharmacopuncture
/
v.25
no.3
/
pp.242-249
/
2022
Objectives: The aim of this work is to evaluate the in vitro antioxidant, hypoglycemic, and antiobesity effects of Euphorbia resinifera extracts and investigate the phenolic constituents and the toxicity of these extracts. Methods: Phytochemical screening was performed to detect polyphenols and flavonoids. Antioxidant activity was evaluated by four methods (DPPH, ABTS, H2O2, and xanthine oxidase inhibition). The hypoglycemic effect was determined by the inhibition of α-amylase and α-glucosidase enzymes in vitro and via a starch tolerance study in normal rats. The antiobesity effect was estimated by in vitro inhibition of lipase. Results: Phytochemical screening revealed that the ethanolic extract was rich in polyphenols (99 ± 0.56 mg GEA/g extract) and tannins (55.22 ± 0.17 mg RE/g extract). Moreover, this extract showed higher antioxidant activity in different tests: the DPPH assay (IC50 = 53.81 ± 1.83 ㎍/mL), ABTS assay (111.4 ± 2.64 mg TE/g extract), H2O2 (IC50 = 98.15 ± 0.68 ㎍/mL), and xanthine oxidase (IC50 = 10.26 ± 0.6 ㎍/mL). With respect to hypoglycemic effect, the aqueous and ethanolic extracts showed IC50 values of 119.7 ± 2.15 ㎍/mL and 102 ± 3.63 ㎍/mL for α-amylase and 121.4 ± 1.88 and 56.6 ± 1.12 ㎍/mL for α-glucosidase, respectively, and the extracts lowered blood glucose levels in normal starch-loaded rats. Additionally, lipase inhibition was observed with aqueous (IC50 = 25.3 ± 1.53 ㎍/mL) and ethanolic (IC50 = 13.7 ± 3.03 ㎍/mL) extracts. Conclusion: These findings show the antioxidant, hypoglycemic, and hyperlipidemic effects of E. resinifera extracts, which should be investigated further to validate their medicinal uses and their pharmaceutical applications.
Shin, Mi-Rae;Kim, SooHyun;Lee, AhReum;Kim, KyeongJo;Kim, SuJi;Lee, Young Cheol;Roh, Seong-Soo
The Korea Journal of Herbology
/
v.32
no.5
/
pp.57-63
/
2017
Objectives : The aim of this study is to search Korean Medicine with the superior inhibitory effect of pancreatic lipase including a possibility as a well-matched sauce material with pork. Methods : We chose 5 samples which have the potent inhibitory effect of pancreatic lipase enzyme among 9 samples. 5 samples were Glycyrrhizae rhizoma, Cinnamomi cortex, Ganoderma lucidum, Syzygium aromaticum, and Schisandra chinensis. Animals were divided into eight groups (n=7). The experimental groups except for normal group were fed 60% high-fat diet. 5 samples were orally administered at a dose of 200 mg/kg body weight and orlistat were orally administrated at a dose of 60 mg/kg body weight for 7 days. Biochemical anaylses of 5 samples were executed based on lipid parameters such as triglyceride (TG) and total cholesterol (TC). Results : Korean Medicines with $IC_{50}$ of below $1mg/m{\ell}$ were Glycyrrhizae rhizoma, Cinnamomi cortex, Ganoderma lucidum, Syzygium aromaticum, and Schisandra chinensis. Body weight change of all drug-treated groups except Glycyrrhizae rhizoma reduced significantly during the experimental period. Orlistat treatment reduced significantly both TG and TC in serum. The significant emission of TG in fece showed in Cinnamomi cortex treatment, whereas Ganoderma lucidum and Syzygium aromaticum showed a tendency to increase without a significance. Besides, Ganoderma lucidum and Schisandra chinensis emitted significantly TC to fece. Conclusions : In conclusion, Cinnamomi cortex may exert anti-obesity effect by directly inhibiting pancreatic lipase, which would prevent the absorption of lipid from the small intestine. Accordingly, Cinnamomi cortex may suggest a high possibility as a well-matched sauce material with pork.
Park, Song-Yi;Hwang, Jin-Taek;Lee, Yun-Kyoung;Kim, Young-Min;Park, Ock-Jin
Journal of Life Science
/
v.19
no.4
/
pp.423-428
/
2009
Selenium was investigated using human origin preadipocytes to see whether it possesses preventive or therapeutic effects for obesity. Unveiling the potential of selenium in the reduction of adipogenesis can help predict the therapeutic capabilities of selenium in obesity. In the present study, the molecular mechanism of the inhibition of adipogenesis by selenium was explored to unravel the involvement of the AMP-activated protein kinase. There is emerging evidence that AMPK, a sensor of cellular energy status, is a possible molecular target of controlling adipocyte differentiation on the basis of discovery that AMPK is responsible for the major metabolic responses to exercise, and integration of nutritional and hormonal signals to modulate feeding behavior or energy expenditure in the hypothalamus. Treatment of selenium resulted in inhibition of the adipocyte differentiation process and induction of mature apoptosis in 3T3-L1 adipocytes. We hypothesized that selenium may exert anti-adipogenic potential though modulating AMPK. We have found that selenium significantly activated AMPK and phosphorylated its substrate acetyl-CoA carboxylase ($ACC-serine^{79}$) during the inhibitory process of adipocytes. Also, the inhibition process of adipocyte differentiation by selenium was comparable to either reveratrol or a synthetic AMPK activator, AICAR (5-aminoimidazole-4-carboxamide-1-${\beta}$-D-ribofuranoside). To evaluate the involvement of AMPK in anti-lipogensis, we applied AICAR and Compound C, an AMPK inhibitor, to 3T3-L1-adipocytes and found that AMPK is required for the adipocyte differentiation blocking process. These results suggest that selenium has a potential to control adipogenesis and that this effect is mediated by AMPK, an essential kinase for both inhibition of adipocyte differentiation and apoptosis of mature adipocytes.
The study was performed to investigate the effects of enzyme treated garlic (EG) and its natural resources composites on lipid levels in serum and liver of rats fed a high fat diet. Four different types of EG-composite extracts prepared: EG and EG + grape peel (EGG), EG + Persimmon (EGP) and EG + Catechu (EGC) by mixed 9.5:0.5, 9:1 and 8:2 (w/w) ratios, respectively. DPPH and ABTS radical scavenging activity in vitro, show the highest in EG + Catechu (EGC) composite by mixed 8:2 (w/w). EG and EG-composites extracts (8:2, w/w) were administered orally to SD-male rats at a concentration of 2.5 g/kg/day for 5 weeks. Total lipid and cholesterol contents in serum were significantly lower in EGC group than control group, and triglyceride content was the lowest in EGP group by 54.29 mg/dL. HDL-cholesterol contents were significantly higher in EGP and EGC groups. LDL-cholesterol content was lower in EG group than EG-composite groups, and VLDL cholesterol content was the lowest in EGP group. GOT, GPT and ALP activity was significantly lower in EGP group. Total lipid, cholesterol and triglyceride contents in liver were significantly lower in EGP and EGC group than control group. Antioxidant activity in serum was the highest in EGC groups by 50.86%, in liver was the highest in EGP groups. TBARS content in serum and liver was the lowest in EGP group. In these results, we suggest that EGP composites could have hypolipidemic and anti-obesity effects in rats fed a high fat diet.
This study examined the chemical composition of lotus root and functionally evaluated a fermented lotus root drink. Electron-donating ability using DPPH along with nitrite-scavenging ability were used to compare the antioxidative activities of unfermented and fermented lotus root drinks. The electron-donating abilities of the unfermented lotus root drink (1%) and fermented lotusroot drink (1%) were 22.55% and 23.88%, respectively. At pH 6.0, the nitrite-scavenging abilities of the unfermented lotus root drink and the fermented lotus root drink (100%) were 27.64% and 40.3%, respectively, and their scavenging ability increased in a dose-dependent manner at all pH values. In order to study the anti-obesity effects of the two drinks, male Sprague-Dawley rats were divided into four groups (A: basal diet, B: high fat diet, C: high fat diet+unfermented lotus root drink, D: high fat diet+fermented lotus root drink). Net weight gains were not significantly different among the four groups. Plasma total cholesterol concentrations significantly decreased in the groups receiving the unfermented and fermented lotus root drinks. Also, plasma total lipid and triglyceride contents were lower in the groups receiving the unfermented and fermented lotus root drinks as compared to the high fat diet group; however, the differences among the three groups were not significant.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.