• 동의생리병리학회지
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• 제23권2호
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• pp.351-359
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• 2009

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. Mori Fructus extract has been known to be effective for the antidiabetic, antihyperlipidemic and antiobesitic prescription, and composed of four crude herbs, The aim of this study was to investigate the effect of Mori Fructus extract in male ob/ob mouse with severe obesity, hyperinsulinemia, hyperglycemia, hyperlipidemia. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57BL/6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 7.5, 15 and 30 mg Mori Fructus extract per 1 kg of body weight for 14 days. The effects of Mori Fructus extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of reactive oxygen species (ROS), MDA+HAE, GSH and also the enzyme activities involved in polyol pathway. Western blotting was performed using anti-AGE, anti-RAGE respectively. Mori Fructus extract lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Mori Fructus extract treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Mori Fructus extract-administered groups. Mori Fructus extract inhibited the generation of ROS in the kidney. MDA+HAE level was increased and the GSH level was decreased in the ob/ob mice, whereas those were improved in the Mori Fructus extract-administered groups. Mori Fructus extract inhibited the expression of AGE, RAGE in the ob/ob mice. The results suggested that Mori Fructus exerted the antidiabetic and antihyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging the ROS, decreasing the MDA+HAE level, increasing the GSH level and inhibiting the expression of AGE, RAGE in the ob/ob mice.

• 대한한의학회지
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• 제30권1호
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• pp.51-63
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• 2009

Objectives: Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}{O_2}^-$ and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the $ONOO^-$, NO, ${\cdot}{O_2}^-$ scavenging and NF-${\kappa}B$ related anti-inflammatory activities of Sotosaja-hwan in ob/ob mice. Methods: Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho-$I{\kappa}B$-${\alpha}$, anti-IKK-${\alpha}$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-YCAM-1 and anti-MMP-9 antibodies, respectively. Results: Sotosaja-hwan inhibited the generation of $ONOO^-$, NO and ${\cdot}{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}{O_2}^-$ and PGE2 were inhibited in the Sotosaja-hwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the protein expression levels of phospho-$I{\kappa}B$-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, YCAM-1 and MMP-9 genes. Conclusions: These results suggest that Sotosaja-hwan is an effective $ONOO^-$, ${\cdot}{O_2}^-$ and NO scavenger and has NF-kB related anti-inflammatory activity in ob/ob mice. Therefore, Sotosaja-hwan might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.

• Journal of Nutrition and Health
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• 제51권6호
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• pp.489-497
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• 2018

본 연구에서는 고지방식이로 유도한 비만군과 저지방식이를 공급한 대조군에서 각 조직의 아연 농도와 아연수송체 발현 수준을 비교하여, 비만 상태가 아연 대사에 미치는 영향을 파악하고자 하였다. C57BL/6J mice를 두 군으로 나누어 각 군당 15마리씩 고지방식이 (비만군) 또는 저지방식이 (대조군)를 총 15주간 공급하였다. 본 연구 결과, 비만군은 대조군에 비해 체중 증가량, 부위별 지방조직, 혈청과 간의 중성지방과 콜레스테롤 농도, 혈청 ALT 및 AST 활성 등이 모두 유의적으로 높게 나타났다. 또한 혈청 렙틴과 염증성 사이토카인인 IL-6의 농도도 비만군에서 유의적으로 증가하였다. 조직 별 아연 농도를 비교한 결과, 간, 소장, 신장, 췌장 등의 측정한 모든 조직에서 비만군이 대조군에 비해 유의적으로 낮게 나타났으며, 대변으로 배설되는 아연 함량은 비만군이 대조군에 비해 유의적으로 높았다. 혈청 아연 농도의 경우 두 군 간 유의적인 차이가 없었으나, 혈청 내 아연-의존 금속효소인 ALP 활성은 비만군에서 대조군에 비해 유의적으로 낮게 나타나 아연의 기능적인 결핍을 확인하였다. 내인성 아연의 체외 배출에 관여하는 췌장 조직에서의 ZnT1 mRNA 수준은 비만군에서 대조군에 비해 유의적으로 높게 나타났으며, 식이 아연 흡수에 관여하는 소장에서의 Zip4와 ZnT1의 mRNA 수준은 두 군간에 유의적인 차이가 없었다. 간 조직의 경우, ZnT1과 Zip10 mRNA이 모두 비만군에서 유의적으로 증가하였다. 이상의 결과를 요약하면, 비만 상태는 아연의 배설 증가와 조직 내 아연 농도 감소를 유발하는 것으로 나타났으며, 이들 아연 대사의 변화는 췌장과 간 조직의 아연 수송체 발현 수준 변화와 밀접한 관련이 있는 것으로 보인다. 비만인들에서 아연 영양상태가 결핍되지 않도록 관심을 가져야 할 것으로 생각되며, 비만으로 인한 아연 대사의 이상 (dysfunction)을 억제하기 위해서는 아연 수송체 발현을 조절할 수 있는 요인들에 대한 이해가 더욱 필요할 것으로 생각된다.

• 한국약용작물학회지
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• 제16권4호
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• pp.225-230
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• 2008

흰양삼, 황기, 감초, 구기자, 뽕나무잎, 갈근, 하고초, 오갈피,오미자, 황금, 산약, 황정, 작약, 생지를 1 : 0.7 : 0.4 : 0.7 : 0.4 :0.7 : 1.1 : 0.9 : 0.4 : 0.4 : 0.7 : 0.7 : 0.9 : 0.9의 비율로 함유한 한약재 조성물의 혈당 및 지질대사 개선효과를 제2형 당뇨동물 모델인 db/db 마우스에 있어서 조사하였다. In vitro에서 한약 재조성물 메탄올 추출물의 ${\alpha}$-glucosidase 저해활성을 측정한 결과, 경구 혈당강하제로 사용중인 아카보스 (20.7%)에 비해 높은 저해활성 (25.2%)을 나타내었다. 4주령의 수컷 db/db 마우스 (C57BL/KsJ, n = 14)를 1주간의 적응기간이 지난 후 2군으로 나누어 대조군에게는 AIN-93G diet를 기본으로 한 basal diet를, 실험군에게는 동결건조된 한약재조성물 가루를 식이의 10% 수준으로 함유한 식이를 6주간 제공하였다. 한약 재조성물의 섭취는 실험동물의 체중 및 식이 섭취량에 유의적인 영향을 주지 않았으나 공복 혈당 (442.5 ${\pm}$ 36.0mg/dL)을 대조군 (489.8 ${\pm}$ 34.6mg/dL)에 비해 유의적으로 감소시켰다 (p < 0.05). 또한 한약재조성물 섭취군의 혈장 콜레스테롤 (159.2 ${\pm}$ 18.4mg/dL) 농도는 대조군 (185.4 ${\pm}$ 13.7mg/dL)에 비해 유의적으로 감소하였으며 (p < 0.05), 혈장 중성지방 농도는 한약재 조성물 섭취군 (99.4 ${\pm}$ 15.0mg/dL)이 대조군 (108.8 ${\pm}$11.0mg/dL)에 비해 낮아지는 경향을 나타내었다. 따라서 한약 재조성물의 섭취는 당뇨동물모델에 있어서 혈당 및 혈장 콜레스테롤 농도를 감소시켜, 당뇨병 개선 및 당뇨합병증 예방에 기여할 것으로 사료된다.

• Nutrition Research and Practice
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• 제18권1호
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• pp.19-32
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• 2024

BACKGROUND/OBJECTIVES: Atherosclerosis is associated with increased inflammation in the visceral adipose tissue (VAT). Vitamin D has been reported to modulate the inflammatory responses of stromal vascular cells (SVCs) and adipocytes in adipose tissue, but the role of vitamin D in atherosclerosis biology is unclear. This study examined the effects of in vitro 1,25-dihydroxyvitamin D₃ (1,25[OH]₂D₃) treatment on the inflammatory responses of SVCs and adipocytes from atherosclerotic mice. MATERIALS/METHODS: C57BL/6J (B6) mice were divided randomly into 2 groups and fed a 10% kcal fat control diet (control group, CON) or 41% kcal fat, 0.21% cholesterol (high fat + cholesterol, HFC) diet (obese group, OB), and B6.129S7-Ldlr^tm1Her/J (Ldlr^-/-) mice were fed a HFC diet (obese with atherosclerosis group, OBA) for 16 weeks. SVCs and adipocytes isolated from VAT were pre-incubated with 1,25(OH)₂D₃ for 24 h and stimulated with lipopolysaccarides for the next 24 h. Proinflammatory cytokine production by adipocytes and SVCs, the immune cell population in SVCs, and the expression of the genes involved in the inflammatory signaling pathway in SVCs were determined. RESULTS: The numbers of total macrophages and SVCs per mouse were higher in OB and OBA groups than the CON group. The in vitro 1,25(OH)₂D₃ treatment significantly reduced macrophages/SVCs (%) in the OBA group. Consistent with this change, the production of interleukin-6 and monocyte chemoattractant protein 1 (MCP-1) by SVCs from the OBA group was decreased by 1,25(OH)₂D₃ treatment. The 1,25(OH)₂D₃ treatment significantly reduced the toll-like receptor 4 and dual-specificity protein phosphatase 1 (also known as mitogen-activated protein kinase phosphatase 1) mRNA levels in SVCs and MCP-1 production by adipocytes from all 3 groups. CONCLUSIONS: These findings suggest that vitamin D can attribute to the inhibition of the inflammatory response in VAT from atherosclerotic mice by reducing proinflammatory cytokine production.

• 동의생리병리학회지
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• 제22권5호
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• pp.1202-1209
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• 2008

Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}\;{O_2}^-$) and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the effects of Ojunghwan on the generation of peroxynitrite ($ONOO^-$), nitric oxide (NO) and superoxide anion radical (${\cdot}\;{O_2}^-$), and on the expression of $NF-{\kappa}B$-dependent inflammatory proteins in ob/ob mice. Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received the standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Ojung-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blot was performed using anti-phospho $I{\kappa}B-{\alpha}$, $anti-IKK-{\alpha}$, $anti-NF-{\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-VCAM-1 and anti-MMP-9 antibodies, respectively. Ojunghwan inhibited the generation of $ONOO^-$, NO and ${\cdot}\;{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}\;{O_2}^-$ and $PGE_2$ were inhibited in the Ojunghwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas that were improved in the Ojunghwan-administered groups. Ojunghwan inhibited the expression of $phospho-I{\kappa}B-{\alpha}$, $IKK-{\alpha}$, $NF-{\kappa}B$ (p50, p65), COX-2, iNOS, VCAM-1 and MMP-9 genes. These results suggest that Ojunghwan is an effective scavenger of $ONOO^-$, ${\cdot}\;{O_2}^-$, NO and $PGE_2$, and has an inhibitory effect on the expression of $NF-{\kappa}B$-dependent inflammatory genes in ob/ob mice. Therefore, Ojunghwan might be used as a potential therapeutic drug against the inflammation process and inflammation- related diseases.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제40권
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• pp.44.1-44.17
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• 2018

Background: Coffee extract has been investigated by many authors, and many minor components of coffee are known, such as polyphenols, diterpenes (kahweol and cafestol), melanoidins, and trigonelline, to have anti-inflammatory, anti-oxidant, anti-angiogenic, anticancer, chemoprotective, and hepatoprotective effects. Therefore, it is necessary to know its pharmacological effect on hepatocytes which show the most active cellular regeneration in body. Methods: In order to determine whether coffee extract has a beneficial effect on the liver, 20 C57BL/6J mice were intraperitoneally injected once with dialyzed coffee extract (DCE)-2.5 (equivalent to 2.5 cups of coffee a day in man), DCE-5, or DCE-10, or normal saline (control), and then followed by histological observation and IP-HPLC (immunoprecipitation high performance liquid chromatography) over 24 h. Results: Mice treated with DCE-2.5 or DCE-5 showed markedly hypertrophic hepatocytes with eosinophilic cytoplasms, while those treated with DCE-10 showed slightly hypertrophic hepatocytes, which were well aligned in hepatic cords with increased sinusoidal spaces. DCE induced the upregulations of cellular proliferation, growth factor/RAS signaling, cellular protection, p53-mediated apoptosis, angiogenesis, and antioxidant and protection-related proteins, and the downregulations of NFkB signaling proteins, inflammatory proteins, and oncogenic proteins in mouse livers. These protein expression changes induced by DCE were usually limited to the range ± 10%, suggesting murine hepatocytes were safely reactive to DCE within the threshold of physiological homeostasis. DCE-2.5 and DCE-5 induced relatively mild dose-dependent changes in protein expressions for cellular regeneration and de novo angiogenesis as compared with non-treated controls, whereas DCE-10 induced fluctuations in protein expressions. Conclusion: These observations suggested that DCE-2.5 and DCE-5 were safer and more beneficial to murine hepatocytes than DCE-10. It was also found that murine hepatocytes treated with DCE showed mild p53-mediated apoptosis, followed by cellular proliferation and growth devoid of fibrosis signaling (as determined by IP-HPLC), and subsequently progressed to rapid cellular regeneration and wound healing in the absence of any inflammatory reaction based on histologic observations.

• 한국식품과학회지
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• 제49권1호
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• pp.90-96
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• 2017

본 연구는 먼저 새송이버섯 추출물인 PEE가 활성화된 면역세포에서 항염증 효과가 있는지 알아보았다. 그 결과 LPS로 자극된 RAW 264.7 세포에 PEE를 처리했을 때 5과 15 mg/mL 등 높은 농도에서 NO를 효과적으로 억제하였다. 그리고 LPS가 유도하는 $IL-1{\beta}$와 IL-6는 5 mg/mL 농도에서는 억제 없었으나, 15 mg/mL 농도에서 현저히 억제하는 효과가 있었다. 다음은 UVB가 유도하는 C57BL/6 마우스 피부손상에 대한 PEE의 개선 효과에 대해서 알아보았다. PEE를 7일간 경구투여한 후 7일, 10, 13일 등 3일 간격으로 하루에 1회씩 UVB ($250mJ/cm^2$)로 마우스 등 피부에 조사하여 피부손상을 유발하였다. UVB 조사 후부터는 PEE를 경구투여와 함께 피부에 도포하여 PEE가 피부 손상에 대한 개선 효과를 조사하였다. 그 결과 PEE 투여군은 UVB로 유도되는 표피두께, 홍반지수 및 멜라닌 지수가 참고약물로 사용한 비타민 C(AA) 투여군과 유사한 개선되는 효과가 있었다. 또한 PEE 투여군은 UVB가 유도하는 비만세포를 비롯한 염중세포 침윤이 현저히 억제되는 효과가 있었다. 이상의 결과를 종합해볼 때 PEE는 항염증 효과와 더불어 UVB가 유도하는 피부손상을 개선하는 우수한 효과가 있어 기능성 식품소재 및 화장품 소재로 활용할 수 있을 것으로 판단된다.

• Clinical and Experimental Reproductive Medicine
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• 제16권2호
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• pp.139-146
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• 1989

The purpose of this study was to examine the qualitative variation of human fetal-cord sera (HCS) and to accept the sera in human lVF-ET program. One hundred and sixteenth RCS were tested with 1772 2-cell embryos of F1 (C57BL x CBA) virgin mice, Ten to sixteenth embryos were cultured in m-KRB medium with a aliquot of each serum (10%, v/v) or with bovine serum albumin(O.4%, w/v) as a control medium. Embryonic development were recorded at every 24hr for 4 days by such events as cellular compaction, cavitation, and hatching. In the control groups of eight assays, 98.1%(106/ 108) of 2-ce1l embryos developed above expanded blastocyst and the embryonic development was unified through the tests. But the developmental pattern in medium with each serum was various. Namely, the sera that supported development of 100% 2-cell embryos to above morula, early blastocyst, expanded blastocyst and hatching blastocyst was 45,7%(53/116) , 35.3%(41/116), 15.5%08/116.) and 6.9-%(8/116), respectively. And the sera that supported development of above 80% 2-cell embryos to the each embryonic stage was 92.2% (107/116), 83.6%(97/116), 63.8%(74/116) and 36.2%(42/116), respectively. Meanwhile two kinds of toxic pattern to the embryonic development were observed in some sera. The first pattern is that some sera arrested development of most embryos in pre- or post-stage of morula or blastocyst. The second pattern is that some sera promoted or arrested a part of embryos in the same dish. The ability of serum was depended on the batch of serum. Finally we could accept 69%(80/116) of the tested sera for human IVF-ET program. The base line for acceptance was the ability that supported above 80% 2-ce1l embryos to blastocyst. But some deterious sera were contained in this range. We cut off about 10% of the sera (83.6% , 97/116) that passed the baseline. This final percent of sera was similar to that of grade N of this study.

• Nutrition Research and Practice
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• 제10권6호
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• pp.629-634
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• 2016

BACKGROUND/OBJECTIVE: The aim of this experiments was to show anti-obesity effects of Korean solar salt from different salt fields in diet-induced obese mice. MATERIALS/METHODS: Diet-induced obesity (DIO) was induced by a high-fat diet (HFD; 45% cal from fat) in C57BL/6J mice for eight weeks. The mice were fed with the designated diets (chow diet for Normal, HFD for Control, 0.47%-salt-mixed HFD for purified salt (PS), Guerande solar salt from France (SS-G), solar salt from Y salt field (SS-Y), solar salts from T salt field (SS-T) and S salt field (SS-S)) for another eight weeks. We checked body weight, food efficiency ratio (FER) and tissue weights (liver and epididymal adipose tissue (EAT)), and observed serum concentrations of triacylglycerol (TG), total cholesterol (TC), leptin and insulin. We also evaluated gene expressions of adipogenic / lipogenic mRNAs of $C/EBP{\alpha}$, $PPAR{\gamma}$ and FAS and beta-oxidation-related factors ($PPAR{\alpha}$ and CPT-1) in liver and EAT. The mineral composition of salt samples were analyzed using inductively coupled plasma optical emission spectrometry (ICP-OES). RESULTS: SS-T and SS-S significantly reduced body weight gain, FER, and weight of EAT compared to control and other samples (P < 0.05). SS-T and SS-S also significantly decreased serum levels of TG, TC, leptin and insulin (P < 0.05). SS-T and SS-S suppressed expressions of adipogenic / lipogenic mRNAs in liver and EAT, while promoting expression of beta-oxidation-related factors. The lowest sodium concentration was observed in SS-T ($30.30{\pm}0.59%$), and the lowest sodium-to-potassium (Na/K) ratio was found in SS-S (17.81). CONCLUSIONS: Our study shows that well-processed Korean solar salt may have anti-obesity effects in vivo, probably owing to its differences in mineral composition and other components, presumably resulting from the manufacturing processes. Further research is needed into the mechanism and to explore optimal manufacturing processes.