Vascular smooth muscle cell (VSMC) apoptosis has been identified in various vascular diseases, including atherosclerosis and restenosis after angioplasty, and has been known to precipitate atherosclerotic plaque instability and rupture. Oxysterols are known as inducers of apoptosis in VSMC, and 7-ketocholesterol (7KC) is the major nonenzymically formed oxysterol in atherosclerotic lesions. The precise mechanism underlying VSMC apoptosis is still poorly understood. In this study, we investigated whether 7KC causes apoptosis, and characterized its apoptotic mechanisms in primary cultured rat aortic VSMC. Cell viability was assessed by MTT assay and trypan blue assay. Apoptosis was assessed by flow cytometry, immunofluorescence, immunoprecipitation, and Western blot analyses. 7KC markedly decreased the VSMC viability in a time- and concentration-dependent manner, and increased the production of 4-hydroxynonenal (HNE), a major end-product of lipid peroxidation, which also decreased the VSMC viability. Pretreatment with 2,4-dinitrophenylhydrazine, a well-known reagent of lipid peroxidation-derived aldehydes, significantly restored the 7KC-decreased viability of VSMC. Furthermore, HNE, as well as 7KC, reduced the level of total Akt, a major mediator of cell survival. The 7KC-decreased level of total Akt was significantly restored by pretreatments with 2,4-dinitrophenylhydrazine and N-acetylcysteine. Lactacystin, a proteasome inhibitor, protected VSMC against apoptosis and Akt degradation, but did not inhibit HNE production. In the immunoprecipitation assay, 7KC increased HNE-modified Akt. From the results, it seems that, in atherosclerotic lesions, 7KC induces HNE production in VSMC, and this HNE binds to Akt, proceeding to proteasomal degradation of Akt, through which mechanism the atherosclerotic plaque instability may be facilitated.
Park, In-Jae;Park, Sung-Hwan;Yun, Ji-Hyun;Choi, Goo-Hee;Kim, Hyun-Jung;Seo, Yun-Hee;Cho, Ju-Hyun
Journal of Food Hygiene and Safety
/
v.32
no.6
/
pp.536-541
/
2017
The object of this study was to investigate the inhibitory effects of Litsea japonica fruit flesh extract (LJF-HE) on gastritis of an stress-induced SD rat model. Rats were randomly divided into six groups: Normal (normal group), Control (stress-induced gastritis), Ranitidine (stress-induced gastritis and ranitidine 50 mg/kg), LJF-HE-L (stress-induced gastritis pretreated with L. japonica fruit flesh extract at 30 mg/kg), LJF-HE-M (stress-induced gastritis pretreated with L. japonica fruit flesh extract at 60 mg/kg), LJF-HE-H (stress-induced gastritis pretreated with L. japonica fruit flesh extract at 120 mg/kg). In groups treated with LJF-HE, gastric mucosal damage and pepsin activity were reduced. Additionally, there were decreases in the expression of cholecystokinin 2 receptor (CCK-2r) in the gastric lesions. The plasma levels of IL-$1{\beta}$ slightly but significantly decreased in LJF-HE treated groups compared to control. The plasma level of PGE2 was also significantly increased in LJF-HE treated groups. These results suggest that LJF-HE has the ability to reduce of the severity stress-induced gastritis.
Kim, Chung-Sook;Ha, Hye-Kyung;Kim, Hye-Jin;Lee, Je-Hyun;Song, Kye-Yong
Korean Journal of Food Science and Technology
/
v.34
no.4
/
pp.710-718
/
2002
It is reported that Pueraria Radix contains phtoestrogens whereas flower, and bud of Pueraria lobata Ohwi were not known. In the present study, we determined the amount of phytoestrogen in each portion of P. lobata Ohwi and carried out therapeutic effects of osteoporosis. The amounts of genistein, daidzein, and formononetin in Pueraria Radix (PR), Pueraria Flos (PF), and young Pueratia Folium (PL) were quantitated using a HPLC system. Proliferation of osteoblast and growth inhibitory effect on osteoclast were measured in order to screen their effects on osteoporosis. Proliferation of osteoblast-like cells (Saos-2) was analyzed by both MTT methods and alkaline phosphatase (ALP) assays. Growth inhibitory effect on osteoclast was also detected as Tartrate resistant acid phosphatase (TRAP) assay. Ovariectomized rat as an in vivo animal model was selected and administrations of PR were 1 g/kg/day (PR-1) and 5 g/kg/day (PR-5) for 9 weeks, respectively. Trabecular bone areas (TBAs) of tibia and lumbar were analyzed usibg histomorphological methods. Results show that PR contains the highest level of daidzein ($10435{\pm}2143\;mg/kg$ of dried herb) and stimulated ALP activity, approximately 160% of the control. Growth inhibitory effect on osteoclast by both PR and daidzein were almost identical with control although $IC_{50}$ of genistein was $5.81{\times}10^{-7}$ M. Increases in body weight of OVX rats were suppressed by administration of PR but wet weights of uterus in PR-5 group were increased (p<0.05). Plasma ALP and HDL-cholesterol levels were decreased following ages (p<0.01), and LDL-cholesterol level was also decreased in PR-5 group at 20 week of age (p<0.01). TBAs of tibia and lumbar in PR-1 and PR-5 groups were higher than those of the control although the values were less than those of the sham group (each p<0.01) In conclusion, administrations of PR prevented loss of TBAs of tibia and lumber in OVX rats, while PL and PF did not (p<0.01).
Journal of the Korea Academia-Industrial cooperation Society
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v.12
no.11
/
pp.4940-4950
/
2011
cis-(3R,5R)-Atorvastatin Ca (1) used for hyperlipidemia have four stereomers. However, It is very difficult to prepare stereoselective stereomers. In this paper, the reduction of 3,5-diketo atorvastatin ester (3) was performed using $Me_4NHB(OAc)_3$ in acetic acid as a reductant and showed excellent stereoselectivity in the double reduction of 3,5-diketo atorvastatin ester (3). As a result, reduction of compound 3 by $Me_4NHB(OAc)_3$ was purely obtained with cis-(3R,5R)-atorvastatin ester (4) of 1.5% and trans-(3R,5S)-atorvastatin ester (5) of 98.5%. Also, cis-(3R,5R)-atorvastatin Ca (1) and trans-(3R,5S)-atorvastatin Ca (7) were used to determine efficacy in the treatment of liver damage and hyperlipidemia induced by a high-fat diet in rats and to study the performance of the January 2010 experient was conducted. As a result, total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), and triglyceride (TG) levels of compound 1 and 7 groups were $93.0{\pm}0.5$, $43.5{\pm}0.8$, $40.4{\pm}1.4$, $45.6{\pm}0.9\;mg/d{\ell}$ and $110.0{\pm}0.7$, $33.3{\pm}0.6$, $65.8{\pm}1.9$, $54.8{\pm}1.2\;mg/d{\ell}$, respectively. Atherogenic index (AI) and cardiac risk factor (CRF) in compound 1 and 7 were $1.14{\pm}0.05$, $2.14{\pm}0.05$ and $2.31{\pm}0.06$, $3.31{\pm}0.06$, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were $51.9{\pm}4.6$, $16.0{\pm}2.1\;IU/{\ell}$ and $75.8{\pm}4.4$, $35.1{\pm}9.7\;IU/{\ell}$. Taken together, while compound 1 treat against high-fat diet-induced hyperlipidemia by attenuating hepatic lipid depots and reducing oxidative stress, compound 7 group had a low curative effect on hyperlipidemia induced by a high-fat diet in rats. These findings suggest that new method about synthesis of stereoselective stereomers and indicate that it may consider using in a clinical trial.
Ahn, Youngsook;Regu, Geberea manuel Meron;Oh, Eun Kyoung;Kwon, Oran
Journal of Nutrition and Health
/
v.50
no.3
/
pp.225-235
/
2017
Purpose: This study aimed to investigate the potential of freeze-dried persimmon powder (Diospyros kaki Thumb.) to protect against dyslipidemia induced by a high-fat/cholesterol diet (HFD) in a rat model. Methods: Fifty Wistar rats were randomly divided into five groups: normal control (NC), high-fat/cholesterol control (HC), tannin in HFD (HT, 1% of diet), immature persimmon in HFD (HI, 7% of diet), and mature persimmon in HFD (HM, 7% of diet). Tannin was used as a positive control. Biochemical, molecular, and histopathological changes were observed in the blood and liver. Results: We confirmed that a high fat/cholesterol diet successfully induced dyslipidemia, which was characterized by significantly altered lipid profiles in the plasma and liver. However, oxidized low-density lipoprotein levels, histopathological damage in the liver, and hepatic triglyceride levels were significantly reduced in all HT, HI, and HM groups compared to those in the HF group. In contrast, plasma apolipoprotein B level was significantly reduced only in the HT and HM groups, whereas reduction of the LDL-C level was detected only in the HI group. Although HF-induced sterol regulatory element-binding protein (SREBP) gene expression was significantly reduced in all treated groups, downstream gene expression levels varied among the different groups; significant reduction of fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl-CoA (HMGCR) gene expression was detected only in the HI group, whereas cholesterol $7{\alpha}$-hydroxylase (CYP7A1) gene expression was significantly elevated only in the HM group. Conclusion: Taken together, the data suggest that protection of LDL oxidation and hepatic lipogenesis might be, at least partly, attributed to tannin in persimmons. However, the identified mechanisms varied up to the maturation stage of persimmon. In the case of immature persimmon, modulation of FAS and HMGCR gene expression was prominent, whereas in the case of mature persimmon, modulation of CYP7A1 gene expression was prominent.
Journal of the Korean Society of Food Science and Nutrition
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v.22
no.2
/
pp.116-126
/
1993
The purposes of this study were to investigate the effect of seleniumc (Se) and vitamin E on activity of enzyme relevant to lipid peroxidation in alcohol administrated rats. Seventy two male rats of Sprague-Dawley strain weighing about 58~62g were divided into 12groups. The dietary Se levels were 0, 0.4 and 10mg and the dietary vitamin E levels were 0 and 150mg per kg diet, respectively. Alcohol-administrated groups received drinking water solution containing 10% of ethanol from the 3-weeks of experimental periods. The obtained experimental results are summarized as follow: The ${\gamma}$-GTP activity in plasma was higher in alcohol administrated groups and high selenium group (HSe) and low selenium group (LSe) than in control groups (CSe). The ${\gamma}$-GOT and GPT activities were higher in alcohol groups. The ${\gamma}$-GTP activity was significantly influenced by alcohol in LSe groups than in other groups. The glutathione peroxidase (GSH-Px) activity of plasma was significantly lower in LSe groups than HSe and CSe groups. The GSH-Px activity of microsomal and cytosolic fraction was slightly lower in alcohol groups and was about a half value lower in HSe and LSe groups than CSe groups. There was negative correlation between plasma Se level and GSH-Px activity of cytosolic fraction in HSe groups (r=- 0.662, p<0.001) and positive correlation in LSe groups (r=0.640, p<0.001). The GSH S-transferase activity in microsomal and cytosolic fraction was slightly higher in alcohol administrated but vitamin E nonadministrated groups, and significantly higher in LSe groups than in other groups. The catalase activity in mitochondria was lower in HSe than CSe groups, but rather higher in LSe groups. The superoxide dismutase (SOD) activity in cytosolic fraction of liver was not found any effect in all groups. The cytochrome P-450 was higher in alcohol groups, but significantly lower in HSe groups. In conclusion, the deficiency of Se and vitamin E develops the hyperoxidation of liver lipid through the increase of activity of enzyme related to the lipid peroxidation and alcohol administration appears to further increase of hyperoxidation of liver lipid.
Journal of the Korean Society of Food Science and Nutrition
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v.35
no.9
/
pp.1185-1193
/
2006
This study investigated the effects of green tea on the disorders of lipid metabolism, oxidative system and hepatic functions induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), using adult male rats (SD) for 3 weeks. These 36 animals were divided into four groups. TCDD ($50{\mu}g/kg$ BW) was intraperitoneally injected at the beginning of experiment. Green tea powder was added 1% or 3% levels in basal diets respectively. Relative weights of thymus were decreased about one-third of control group, but those of liver, brain and testis were significantly increased in rats treated TCDD. Neutrophill% and lymphocyte% by TCDD treatment was improved by green tea diets. In liver functional enzyme, elevation of glutamic oxaloacetic transaminase (GOT) and alkaline phosphatase (ALP) activities due to TCDD treatment was lowered by green tea diets. The concentrations of serum and liver lipids were significantly increased by TCDD treatment, however, those of serum and liver triglyceride tended to decrease by green tea diets. Fecal lipid excretion was increased in rats fed green tea diets. Especially, fecal total cholesterol level was significantly elevated by 3% green tea diets. The activities of superoxide dismutase (SOD) were increased in rats fed 3% green tea diets. Increment of benzphetamine N-demethylase (BPND) activity by TCDD treatment was declined by 1% green tea diets. These results indicate that green tea can exert improving effects on liver lipid accumulation and unfavorable hepatic functions, and elevate antioxidation.
Journal of the Korean Society of Food Science and Nutrition
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v.12
no.4
/
pp.323-335
/
1983
The inhibitory effects of the extract and crude saponin of red and white ginsengs on lipoperoxide formation in vitro and in vivo were studied and correlated with anti-aging. To this end, antioxidant activity, induction period and lipoperoxide were measured by the methods of EDA, POV and TBA value. And also superoxide dismutase and peroxidase activity were measured by pyrogallol autoxidation method (${\Delta}A$ 420/min) and initial velocity(${\Delta}A$ 436/min), respectively. From HPLC analysis, the PT/PD ratio of red and white ginsengs was found to be 0.561% and 0.401%, respectively, and red ginseng increased the PT/PD ratio in comparison with white ginseng. The EDA activity of red ginseng was higher than that of white ginseng; red ginseng showed stronger antioxidative effect than white ginseng. The inhibitory effect of red ginseng was lower than that of white ginseng during the induction period. It was proved that high molecular coloring substance was deeply related to the initial stage of lipoperoxidation. There was no significant difference between red and white ginsengs in both in vitro and intraperitoneal administration experiments, and red ginseng was more effective than white ginseng in longterm administration. And also inhibitory effect on lipoperoxide formation was mainly occurred in liver, suggesting that the function of liver played an important role in anti-aging actions. From the measurement of superoxide dismutase(SOD) activity for both ginseng groups intraperitoneally and orally administered, it was found that red ginseng group administered extract and crude saponin showed remarkable inhibitory effects in comparison with white ginseng. In particular, orally administered group showed more stronger inhibitory effect on lipid peroxidation in comparison with intraperitoneally administered group. It was also found that the continuous oral administration was more effective than temporary administration. Red ginseng was more notable anti-aging effect in comparison with white ginseng in vivo, and this may be due to the increase of SOD activity in rat-liver. Peroxidase activity also showed similar trend to SOD activity in vitro and in vivo experiments. Red ginseng was not only superior to white ginseng for preservation but also for biochemical and pharmaceutical efficacy.
Journal of the Korean Society of Food Science and Nutrition
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v.36
no.9
/
pp.1128-1133
/
2007
This study was conducted to examine antioxidative activity and lipid composition from different parts and supplement flesh and skin of Codonopsis lanceolata in vivo. Forty six-week-old white Sprague Dawley rats were divided into 5 groups and fed with experimental diet for six weeks to measure antioxidant enzymes activities and lipid composition in blood and liver microsome. The activity of glutathione peroxidase in blood was high in all groups supplemented with Condonopsis lanceolata and the difference was observed in accordance with the supplemented part rather than the supplemented level. However, glutathione reductase activity and the content of malondialdehyde (MDA) in blood showed difference depending on the level of supplementation rather than the supplemented part. The content of liver MDA in all groups supplemented with Condonopsis lanceolata was lower than that in the control group. As the level of skin supplementation increased, an increase in glutathione peroxidase activity was also observed. Only in the group that 5% of Condonopsis lanceolata skin was supplemented, the glutathione reductase activity was higher than in the control group. Total cholesterol and LDL-cholesterol of blood in the group supplemented with Condonopsis lanceolata flesh or skin were significantly lower than those in control group. HDL-cholesterol in blood was high when the flesh of Condonopsis lanceolata was supplemented. Total cholesterol and triglyceride in liver of the group supplemented with Condonopsis lanceolata flesh or skin were significantly lower than those in control group. In summary, this animal test showed that the supplementation of Condonopsis lanceolata, flesh or skin, generally improved the antioxidative effect of diet and lipid composition.
Background: Korean ginseng (KG) has been used as a general tonic, and for voiding dysfunction for a long time in oriental society. However, scientific basic studies on the use of KG, have been rare, especially for voiding and erectile dysfunction. This study was performed to investigate the effects of KG on voiding and erectile function by examining the effects of total saponin (TS) on the bladder, urethral and penile cavernosal smooth muscle. Materials and methods: To examine the effects of TS, NewZeland white rabbits were used to obtain tissue strips from the smooth muscle of the bladder, proximal urethra and corpus cavernosum. Adult Sprague Dawley rats were used to examine the changes in urodynamic findings and penile erection after administration of TS. Results: In proximal urethral strips, the rate of relaxation of the proximal urethra was increased from $9.0{\pm}2.9$ to $33.7{\pm}4.8%$ in a dose-dependent manner when the concentration of TS was added accumulatively from 0.25 mg/ml to 4.0 mg/ml (p<0.05). However, no significant response was observed in the bladder strips within these concentration ranges. For the corpus cavernosal strips, the rate of relaxation ranged from $5.8{\pm}2.1$ to $36.7{\pm}5.8%$, increasing in a dose-dependent manner when TS was increased from 1.0 mg/ml to 4.0 mg/ml (p<0.05). After administration of 0.1 ml of TS (32 mg/ml) in the rat, the bladder pressure was $37.5{\pm}8.5$ mmHg at $52.1{\pm}7.0$ sec. during isovolumetric bladder contraction, showing no significant differences from $35.7{\pm}7.8mmHg$ and $50.7{\pm}7.2$ sec, respectively, before treatment. However, when 0.1 ml of TS (32 mg/ml) was administered, the relative reduction of urethral pressure was $6.9{\pm}0.5mmHg$ at $62{\pm}7.5$ sec, which was significantly higher compared to $4.6{\pm}1.1mmHg$ at $45{\pm}10$ sec before treatment (p<0.05). For the cavernosal injection study, the change in intracavernosal pressure (${\Delta}ICP$) was examined after administering 0.1 ml of TS. The cumulative additions of TS at concentrations from 0.5 mg/ml to 32 mg/ml increased ${\Delta}ICP$ from $1.3{\pm}0.5$ to $21.3{\pm}7.8mmHg$ in a dose-dependent manner (p<0.05). The duration of tumescence was from $0.3{\pm}0.1$ to $5.2{\pm}0.2$ min, showing dose-dependent increase (p<0.05). Furthermore, the cumulative addition of TS at concentrations from 0.5 mg/ml upto 32 mg/ml did not cause any significant change in systemic blood pressure. Conclusion: These results suggest that ginseng improves voiding functions, which is mainly achieved by TS relaxing the proximal urethra, the most important part of the bladder outlet function. In addition, ginseng safely induced a penile erection hemodynamically by relaxing the corpus cavernosum.
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