• Title/Summary/Keyword: LDL/HDL

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The effects GeongshinhaeGihwan 1(GGT1) has on the hGHTg (human growth hormone transgenic) obese male rats' blood-antiobestic index (형질전환 비만모델 수컷 hGHTg rats에서 경신해지환(輕身解脂丸)이 혈중 항비만지표에 미치는 영향)

  • Jung, Yang-Sam;Tsung, Pei-Chin;Choi, Seung-Bae;Kim, Gyeong -Cheol;Shin, Soon-Shik
    • Herbal Formula Science
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    • v.13 no.2
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    • pp.1-16
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    • 2005
  • Objectives: To find out the effects GGTl, an antiobestic drug widely used in clinics, has on the blood-antiobestic index and the toxicity index using the data from the hGHTg obese male rats. We looked closely into both of the two indices because GGTl antiobestic effect can happen not only by pharmacological action, but also by its toxicity. Also, we verified the difference in effect between GGTl and reductil (sibutramine), which has been approved by the FDA of the United States. Methods: After performing the experiments for 8 weeks on the hGHTg obese male rats divided into three groups: the control group, the GGTl group, and the reductil (RD) group, we anesthetized the rats with Diethyl ether and took a 3ml blood sample from the heart. Then, after coagulating the blood in room temperature by using the plasma separator, we centrifuged it for 25 minutes in 3,000rpm using the high-speed refrigerated centrifuge. We kept the separated plasma in a deep freezer at $-80^{\circ}C$, and repeatedly measured the antiobestic index and the toxicity index twice using the hematology biochemistry analyzer. Also, in order to judge the indirect toxicity index, we separated liver from kidney and observed them. Results: When we looked at the results of the analysis of covariance on the measuring elements related to the antiobestic index (TC, HDL, LDL, TG, and GLU), there was no significant difference among the groups in all measuring elements. Also, the results of the analysis of covariance on the two roups (RD group and GGTl group) showed that the p-values had no significant difference under the level of significance 0.05. When we looked at the result of the analysis of covariance on the measuring elements related to the toxicity index (GOT, GPT, GGT, CREA, UA, ALB, and TP), we could see that the p-values in GPT, ALB, and TP have a significant difference among the groups. Also, the results of the analysis of covariance about the measuring elements related to the toxicity index on both groups, RD group and GGTl group, showed no significant difference in the p-values of all of the measuring elements in the two groups, RD and GGTl group. Conclusions: In conclusion, through this experiment, the safety of GGTl has been approved, and although the verification on its medical effect has not been clearly approved, when we consider the fact that it belongs to the same group as reductil, an antiobestic drug approved by the FDA of the United States, we could indirectly verify that GGTl has an antiobestic effect. We believe that when doing a sample design for a future experiment, it needs to be performed on a greater sample size based on the power analysis that needs to be performed primarily in experiments, and a more accurate verification is needed through more systematic experiment plans.

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Effects of Germanium-fortified Yeast on the Serum Lipids and Immune Cell Subset (게르마늄강화효모가 혈청지질 및 면역세포변화에 미치는 영향)

  • Lee, Sung-Hee;Oh, Sun-Woo;Rho, Sook-Nyung;Lee, Bog-Hieu;Lee, Hyun-Joo;Jin, Dong-Kyu
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.6
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    • pp.683-689
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    • 2006
  • This study was established to investigate the effect of germanium-fortified yeasts on the serum lipid composition and immune system of human body. All 50 subjects with the age range of $50{\sim}75$ were entered in this clinical trial for 6 months. The effects were determined by the proliferative responses of immune-mediated cells, T-cell, B-cell and NK-cell during daily supplementation with/without germanium-fortified yeast. The results of hematology and blood chemistry didn't show any significant differences during administration periods. Serum lipid compositions also didn't show any significant differences during administration periods except triglyceride (TG) and VLDL-cholesterol. TG and VLDL-cholesterol levels were increased significantly by the consumption of germanium-fortified yeast (p<0.05). Immune mediated T-celt and NK-cell didn't increased in both control and test group supplemented with germanium fortified yeast, while B-cell increased in the germanium fortified yeast group after 8 week (p<0.05). Also $TNF-{\alpha}$ increased in the group of germanium fortified yeast after 8 week (p<0.05) but not in the control group. From the above results, germanium fortified yeast is expected to be useful on the improvement of the cellular immune response and protection of organs from various chronic diseases.

Effect of Brown Seaweed Waste Supplementation on Lactational Performance and Endocrine Physiology in Holstein Lactating Cows (미역부산물의 첨가가 홀스타인 비유우의 비유성적과 내분비생리에 미치는 영향)

  • Lee, H.G.;Hong, Z.S.;Li, Z.H.;Xu, C.X.;Jin, X.;Jin, M.G.;Lee, H.J.;Choi, N.J.;Koh, T.S.;Choi, Yun-Jaie
    • Journal of Animal Science and Technology
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    • v.47 no.4
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    • pp.573-582
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    • 2005
  • This study was conducted to investigate effects of the brown seaweed waste(BSW) supplementation on milk production and related endocrine response in serum in Holstein dairy cows. A total of 14 Holstein dairy cows(initial mean live weight 625kg, average lactation days 225, Reproduction 2.4) were randomly allocated into control(basal diet) and treatment groups (4% BSW/basal diet) with 7 replications for 90 days. Dry matter intake was not affected by brown seaweed waste supplementation, but daily milk yield(kg) at the last experiment significantly increased (6.25kg) in treatment group compared with control group(p<0.05) at the last experiment. The plasma insulin-like growth factor(IGF)-1, triiodothyronine($T_3$) and thyroxine($T_4$) levels were significantly increased in treatment group compared with control group(p<0.05), although the concentration of plasma growth hormone(GH) was not significantly different. Milk composition was not significantly different between groups. The somatic cell count(SCC) in milk were significantly reduced in treatment group compared with control group(p<0.05), but antibodies(total IgG, G1, G2) were not significantly different between groups. Therefore we strongly believe that the increased milk yield is related to metabolic hormones as IGF-1, $T_3$ and $T_4$ and the mechanism of reducing SCC in milk must do more study related nonspecific immunsystem in the future.

Effects of Seomaeyakssuk (Artemisia argyi H.) Vinegar on Lipid Metabolism in Rats Fed a High-Fat and High-Cholesterol Diet (섬애약쑥 식초가 고지방-고콜레스테롤 급이 흰쥐의 체내 지질대사에 미치는 영향)

  • Shin, Jeong Yeon;Kang, Jae Ran;Shin, Jung Hye;Seo, Weon Taek;Byun, Hee Uk;Choi, Jin Sang;Kang, Min Jung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.7
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    • pp.779-789
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    • 2017
  • The effects of orally administered Seomaeyakssuk (Artemisia argyi H.) vinegar on lipid metabolism in Sprague-Dawley rats fed a high-fat and high-cholesterol (HFC) diet were analyzed. The experimental animals were divided into five groups: a normal diet group (normal, N), HFC diet group (control, C), HFC diet with lovastatin at 20 mg/kg body weight (B.W.) group (positive control, PC), HFC diet with malt vinegar group (TM), and HFC diet with Seomaeyaksuk vinegar group (TS) (2 mL/kg B.W.). After 4 weeks of feeding rats the experimental diet, contents of serum total lipids and total cholesterol levels of TM and TS groups were significantly lower than those of the PC group. Triglyceride contents of the TM and TS groups were not significantly different from those of the PC group but significantly lower than those of the C group. Content of serum high density lipoprotein-cholesterol was significantly lower than that of the N group but higher than that of the C group. Low density lipoprotein-cholesterol content of serum was 190.68 mg/dL in the TS group, which was the lowest except for the N group. Aspartate transaminase and albumin transaminase activities as a measurement of liver damage index were not significantly different between the TM, TS, and C groups. Serum thiobarbituric acid reactive substance content of the TS group was reduced to a similar level as the N group but was lower than that of the C group in the liver and significantly higher than that of the N group. Antioxidant activity of the TS group was 55.69% in serum, which was a similar to that of the N group, and was 52.39% in the liver, which was not significantly different than that of the C group. From these results, we conclude that Seomaeyakssuk vinegar improves serum lipid content as a result of the complex action of vinegar, an active ingredient of Seomaeyakssuk and a product of the fermentation process.

Mechanism by which periodontitis may contribute to atherosclerosis (치주염이 동맥경화에 기여하는 기전에 관한 연구)

  • Han, Seung-Hee;Kim, Kyung-Hwa;Yang, Seung-Min;Chung, Hyun-Ju;Choi, Yoon-Sik;Han, Soo-Boo;Chung, Chong-Pyoung;Rhyu, In-Chul
    • Journal of Periodontal and Implant Science
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    • v.32 no.4
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    • pp.837-846
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    • 2002
  • 그람 음성균의 감염에 의한 만성 염증질환인 치주염이 동맥경화를 동반한 허혈성 심장질환 (협심증이나 심근 경색)을 일으킬 수 있는 위험인자로 작용할 수 있다는 보고가 있었다. 그러나, 그 기전에 관해서는 명확하게 알려져 있지 않다. 작용기전의 하나로서, 치주염에 의해 치주조직에서 국소적으로 생긴 염증성 싸이토카인(IL-1${\beta}$, IL-6, $PGE_2$, TNF-${\alpha}$)이 혈행을 따라 이동하여 심혈관에서 동맥경화를 일으킬 수 있다는 가설이 제시되고 있는데, 이 가설을 검증해 보고자 한다. 서울대학교 병원 순환기 내과에 불안정 협심증이나 심근경색으로 입원한 환자 및 과거 이 질환의 병력을 갖고 있거나 검진 목적으로 내원하여 관상동맥 조형술을 받은 환자들 중 동맥경화로 진단받은 사람을 실험군(24명)으로 하고, 동맥경화로 진단받지 않은 사람을 대조군(12명)으로 하였다. 치주질환의 활성도를 나타내는 치은 지수, 치태 지수, 치주낭 깊이, 부착 상실을 측정하였다. Paper strip을 실험대상 치아(Ramfjord's teeth)들 중에서 가장 깊은 치주낭을 가진 두 개의 치아를 택하여 각 치아의 가장 깊은 치주낭에 30초간 삽입한 후 밀폐된 plastic tube에 넣고 ELISA kit를 이용하여 IL-1${\beta}$, IL-6, TNF-${\alpha}$, $PGE_2$의 농도를 측정하였다. 환자의 plasma에서도 동일한 싸이토카인의 농도를 측정하였다. 설문조사를 통해 동맥경화의 위험 인자로 간주되어온 고혈압, 당뇨, 가족력, 심근경색이나 협심증의 기왕력, 흡연의 유무를 기록하였다. 혈액검사를 하여 total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, WBC, CRP (C-reactive protein)의 농도를 측정하였다. 치주조직에 대한 임상 검사 결과 치은의 염증상태를 나타나는 지표인 치은 지수에서만 실험군이 대조군에 비해 유의할 정도 (p=0.0174)로 높게 나타났고, 만성적인 염증의 결과로 인한 치조골의 사실 정도를 나타내는 치주낭 깊이나 부착 상실에서는 유의할 만한 차이를 보이지 않았다. 치주낭에서 측정한 염증성 싸이토카인 중 IL-1${\beta}$, $PGE_2$가 실험군에서 유의할 만한 차이 (p=0.005, 0.022)를 보이며, 더 높은 농도로 나타났고, TNF-${\alpha}$는 대조군에서 유의성 있게 (p=0.009) 높게 나타났다. 그러나, plasma의 싸이토카인이나, serum lipid/lipoprotein, C-reactive Protein, WBC는 유의할 만한 차이를 보이지 않았다. 또한 치은열구액내의 싸이토카인과 이에 상흥하는 싸이토카인 간에 상관관계는 관찰되지 않았다. 다변량 로지스틱 회귀분석 결과, 치은열구액내의 IL-1${\beta}$와 TNF-${\alpha}$ 만이 동맥경화와 유의성 있는 관련성을 보였고, 특히 IL-1${\beta}$와 교차비는 273으로 상당한 관련성을 보여주었다. 결론적으로, 치주조직에서 국소적으로 생긴 염증성 싸이토카인이 그대로 혈행으로 이동하여 혈장내의 싸이토카인 농도를 높이는 것은 아니다. 그러나, 치주염으로 인해 치은열구내액내에 국소적으로 증가된 염증성 싸이토카인은 동맥경화와 상당한 관련성을 가진다.

Effect of cooling water and inverse lighting on short chain fatty acid and blood lipid of broiler chickens in closed poultry house during hot weather (혹서기 무창계사에서 육계의 혈액지질 및 짧은 사슬지방산에 관한 역전점등과 냉각수 효과)

  • Park, Sang-Oh;Park, Byung-Sung;Hwangbo, Jong;Choi, Hee-Chul
    • Journal of the Korean Applied Science and Technology
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    • v.31 no.1
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    • pp.31-43
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    • 2014
  • This experiment evaluated the interaction effect of extreme heat diet(EHD), inverse lighting, and cool water on the growth performance of broiler chickens under extreme heat stress. There were 4 experimental groups (T1: EHD 1, 10:00-19:00 dark, 19:00-10:00 light, cold water $9^{\circ}C$; T2: EHD 2, 10:00-19:00 dark, 19:00-10:00 light, cold water $9^{\circ}C$; T3: EHD 1, 09:00-18:00 dark, 18:00-09:00 light, cold water $14^{\circ}C$; T4: EHD 2, 09:00-18:00 dark, 18:00-09:00 light, cold water $14^{\circ}C$), each group composed of 25 broilers and the experiment was repeated 3 times. EHD 1 contained soybean oil, molasses, methionine and lysine. EHD 2 contained all nutrients of EHD 1 and vitamin C additionally. As a result, T1 and T2 displayed higher body weight increase and diet intake compared to T3 and T4 (p<0.05). The weights of their liver and gizzard were similar but the weights of the thymus and bursa F were higher for T1 and T2 compared to that of T3 and T4 (p<0.05). It was observed that T1 and T2 displayed higher concentrations of blood triglyceride, total cholesterol, HDL-C and blood sugar compared to that of T3 and T4 but LDL-C level was higher for T3 and T4 compared to that of T1 and T2 (p<0.05). T1 and T2 displayed higher levels of immunity substances such as IgG, IgA and IgM compared to T3 and T4 but the blood level of corticosterone displayed to be lower for T1 and T2 compared to T3 and T4 (p<0.05). The T1 and T2 contained a higher amount of fecal lactobacillus compared to that of T3 and T4 but the T3 and T4 contained a higher amount of fecal E. coli, total aerobic bacteria, coliform bacteria compared to that of T1 and T2 (p<0.05). T1 and T2 displayed higher concentrations of cecal acetic acid, propionic acid and total short chain fatty acids compared to T3 and T4 but T3 and T4 displayed higher concentrations of butyric acid, isobutyric acid, valeric acid and isovaleric acid compared to T1 and T2 (p<0.05). These results have been observed that broiler chickens exposed to extreme heat stress with feeding EHD, inverse lighting and cold water would improve blood lipid, and elevate the production of immunity substance, beneficial microorganisms, and short chain fatty acids. This provision would also reduce the blood sugar consumption rate as energy sources and these effects will improve the growth performance of the broilers exposed to extreme heat.

Effects of Natural Complex Food on Specific Enzymes of Serum and Liver and Liver Microstructure of Rats Fed a High Fat Diet (지방간 환자를 위한 생식용 천연복합식품이 고지방식이를 급여한 흰쥐의 혈청, 간장의 효소 및 간조직 구조에 미치는 영향)

  • Lee, Eun;Kim, Wan-Jae;Lee, Young-Joo;Lee, Mi-Kyung;Kim, Pan-Gu;Park, Yeon-Jung;Kim, Soo-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.2
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    • pp.256-262
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    • 2003
  • In order to design and develop a product that can treat the fatty liver, natural complex food with all natural ingredients was developed and supplemented to rats with high fat diet to induce fatty liver. As a result, when the amount of natural complex food was increased in diet of subjects, the activities of the blood serum AST, ALT, ALP, 3-GT and LDH were decreased. The total protein concentration levels of the 30% and the 50% natural complex food groups did not show changes in respect to the control group, but the 100% natural complex food groups showed significant decrease (p<0.05). Likewise, the amount of blood serum albumin in the 30% and the 50% natural complex food groups did not show improvement, but the 100% natural complex food did showed significant changes (p<0.05). The amount of blood serum triglyceride decreased as the amount of natural complex food was increased. In order to investigate the appearances of the accumulated fat in the liver, the animals were dissected. Livers of the control group (no natural complex food) were appeared as a white color, which means serious fat accumulation. However, all the natural complex food groups (30,50 and 100% natural complex food) showed noticeable decrease of fat content. Even the histology showed that livers of the control group had expansion of the fat, but a11 the natural complex food groups had e decreased as the contents and continued to show destroyed fatty cells. By observing the biological numeric data, the physical appearance and the history of the fatty liver, it is highly expected that natural complex food is very effective in treating the liver damaged -by the to fat and the cholesterol.

Effects of Stem Bark Extracts of Cornus walteri Wanger on the Lipid Lowering, Anti-oxidative Activity and Concentration of Proinflammatory Cytokines in Rat Fed High Fat Diet (모래지엽(毛棶枝葉)(Cornus walteri Wanger) 추출물이 비만 쥐의 지질강하, 항산화효과 및 전염증성 cytokines 농도에 미치는 영향)

  • Park, Won-Hyung;Cha, Yun-Yeop
    • Journal of Korean Medicine Rehabilitation
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    • v.19 no.4
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    • pp.59-78
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    • 2009
  • Objective : This study was designed to examine the effects of stem bark extracts of Cornus walteri Wanger on the lipid lowering, anti-oxidative activity and concentration of proinflammatory cytokines in hyperlipidemic rat. Methods : Male rats weighing $195.21{\pm}5.85g$ fed high fat diet for 8 weeks and 40 rats(above 400 g) were divided into 4 groups. Each groups were divided into a control group and 3 experimental groups. We fed a control group of rats a basal diet and administered normal saline(100 mg/kg, 1 time/1 day) for 4 weeks. And we fed each experimental group of rats Basal diet and administered an extract of Cornus walteri Wanger(100 mg/kg, 200 mg/kg, 300 mg/kg, 1 time/1 day) for 4 weeks. At the end of the experiment, the rats were sacrificed to determine their chemical composition. We measured lipid of plasma and liver, concentration of proinflammatory cytokines, anti-oxidative activity and gene expression. Results : 1. Concentration of plasma free fatty acid, LDL-cholesterol showed a tendency to decrease in Cornus walteri Wanger ext. groups. Concentration of plasma triglyceride, total cholesterol showed a significantly decrement in all Cornus walteri Wanger ext. group than that of control group. HDL-cholesterol showed a significantly increment in the 300 mg/kg Cornus walteri Wanger ext. group. 2. Concentration of liver total cholesterol showed a tendence to decrease in Cornus walteri Wanger ext. groups. Concentration of triglyceride liver showed a significantly decrement in all Cornus walteri Wanger ext. group than that of control group. 3. Concentration of plasma and liver TBARS showed a tendence to decrease in Cornus walteri Wanger ext. groups. The values of GSH-Px, SOD and CAT activity showed a significantly increment in the 300 mg/kg Cornus walteri Wanger ext. group than that of control group. 4. The values of plasma AST and ALT activity showed no significantly different in all treatment groups. 5. Concentration of plasma $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ showed a tendency to decrease in the Cornus walteri Wanger ext. groups. However the concentration of IL-10 in the 200 and 300 mg/kg Cornus walteri Wanger ext. groups showed a significantly increment than that of control group. Concentration of liver $IL-1{\beta}$, $TNF-{\alpha}$ and IL-10 showed no significantly difference in all treatment groups. However concentration of IL-6 in the 200 and 300 mg/kg Cornus walteri Wanger ext. groups showed a significantly decrement than that of control group. 6. In the analysis of RT-PCR, gene expression of $TNF-{\alpha}$, Apo-B, Apo-E and leptin in the Cornus walteri Wanger ext. groups showed a lower expression than that of control group. 7. The ratio of $TNF-{\alpha}$, Apo-E and leptin expression per $\beta$-actin expression in the 200 and 300 mg/kg Cornus walteri Wanger ext. showed a significantly decrement than that of control group. The ratio of Apo-B expression per $\beta$-actin expression in the 300 mg/kg Cornus walteri Wanger ext. showed a significantly decrement than that of control group. Conclusions : According to above results, in lowering lipid effect, antioxidative activity and antiinflammatory effect, the Cornus walteri Wanger ext. gives positive effect.

Effect of Pinus densiflora Extract on Blood Glucose Level, OGTT and Biochemical Parameters in Streptozotocin Induced Diabetic Rats (솔잎증류액의 투여가 Streptozotocin으로 유도한 당뇨쥐에서 혈당, 구강내당능검사, 혈액 성분에 미치는 영향)

  • Kim, Shin-Hee;Hwang, Seock-Yeon;Park, Oh-Sung;Kim, Moo-Kang;Chung, Young-Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.7
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    • pp.973-979
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    • 2005
  • To investigate the effect of Pinus densiflora on biochemical parameters in type I diabetic rats, we evaluated the changes of body weight, fasting blood glucose level, oral glucose tolerance test (OGTT) and biochemical parameters after the intraperitoneal injection of distilled solution of Pinus densiflora in streptozotocin (STZ)­induced rats. Thirty-seven male Sprague Dawley rats $(180\pm10g)$ were divided into four groups; diabetic mellitus (DM) group received STZ (50 mg/kg BW, i.v.); low level of pine extract (LP) group received Pinus densiflora (5 mg/kg BW, i.p.), high level of pine extract (HP) group received Pinus densiflora (10 mg/kg BW, i.p.) after the single injection of STZ (50 mg/kg BW, i.v.), respectively. Normal control (NC) group received saline. The change of fasting blood glucose level and OGTT were measured using glucocard II, and the change of biochemical parameter were measured by Automatic Chemistry Analyzer (Hitach-747, Japan). Mean body weight change of DM group was retarded greatly by STZ-exposure. While, body weights of LP and HP groups were progressively increased with some fluctuation, although the increase rates were slower than that of NC group. Fasting blood glucose levels of LP and HP groups were reduced by Pinus densiflora injection, although the fasting blood glucose levels were higher than that of NC group. The results of OGTT was significantly improved in both of LP and HP group compared to DM group. Increases of blood glucose, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and blood urea nitrogen (BUN) levels by STZ-exposure were attenuated by the Pinus densiflora treatment (p<0.05). From the results, it was suggested that Pinus densiflora has a tendency to decrease STZ-induced toxicity in terms of monitoring fasting blood glucose, OGTT and some biochemical parameters of rat.

Dietary Effects of Post-fermented Green Tea by Monascus pilosus on the Body Weight, Serum Lipid Profiles and the Activities of Hepatic Antioxidative Enzymes in Mouse Fed a High Fat Diet (Monascus pilosus로 발효시킨 후발효 녹차가 고지방 식이 마우스의 체중과 혈청 지방함량 및 간 조직 항산화계 효소활성에 미치는 영향)

  • Lee, Sang-Il;Lee, Ye-Kyung;Kim, Soon-Dong;Yang, Seung-Hwan;Suh, Joo-Won
    • Journal of Applied Biological Chemistry
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    • v.55 no.2
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    • pp.85-94
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    • 2012
  • The anti-obese, hypolipidemic and hepatoprotective effects of post-fermented green tea by Monascus pilosus was tested with mice fed with high-fat diet for 7 weeks. The body weight gain and feed efficiency ratio (FER) in normal control group (NC), CHA (2% non-fermented green tea powder supplemented high-fat diet group) and mCHA (2% green tea powder post-fermented by M. pilosus supplemented high fat diet group) groups were significantly lower than those of high fat diet control group (HC). Epididymal fat weight in mCHA and NC were significantly lower than HC. The hepatic lipid peroxide was dramatically higher in HC than that of NC and was significantly lower in CHA and mCHA. In addition, dehydrogenase type activity of xanthine oxidoreductase in HC was lower than that of NC, but significantly higher than CHA and mCHA. In histopathological findings, hepatic fat accumulation in HC was higher than that of NC, CHA and mCHA. Antiobese, hypolipidemic and antifatty liver effect of green tea powder post-fermented by M. pilosus was slightly higher than that of non-fermented green tea. In conclusion, the constituents of green tea fermented by M. pilosus has been proven to not only inhibit obesity and hyperlipidemia but also decrease the hepatic fat accumulation in high fat diet-induced obese mice.