• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.239-249
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• 2021

The present study explored the therapeutic potential of hydrogen sulfide (H2S) in restoring aging-induced loss of cardioprotective effect of remote ischemic preconditioning (RIPC) along with the involvement of signaling pathways. The left hind limb was subjected to four short cycles of ischemia and reperfusion (IR) in young and aged male rats to induce RIPC. The hearts were subjected to IR injury on the Langendorff apparatus after 24 h of RIPC. The measurement of lactate dehydrogenase, creatine kinase and cardiac troponin served to assess the myocardial injury. The levels of H2S, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), nuclear factor erythroid 2-related factor 2 (Nrf2), and hypoxia-inducible factor (HIF-1α) were also measured. There was a decrease in cardioprotection in RIPC-subjected old rats in comparison to young rats along with a reduction in the myocardial levels of H2S, CBS, CSE, HIF-1α, and nuclear: cytoplasmic Nrf2 ratio. Supplementation with sodium hydrogen sulfide (NaHS, an H2S donor) and l-cysteine (H2S precursor) restored the cardioprotective actions of RIPC in old hearts. It increased the levels of H2S, HIF-1α, and Nrf2 ratio without affecting CBS and CSE. YC-1 (HIF-1α antagonist) abolished the effects of NaHS and l-cysteine in RIPC-subjected old rats by decreasing the Nrf2 ratio and HIF-1α levels, without altering H2S. The late phase of cardioprotection of RIPC involves an increase in the activity of H2S biosynthetic enzymes, which increases the levels of H2S to upregulate HIF-1α and Nrf2. H2S has the potential to restore aging-induced loss of cardioprotective effects of RIPC by upregulating HIF-1α/Nrf2 signaling.

• Biomolecules & Therapeutics
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• v.29 no.4
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• pp.399-409
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• 2021

1,2-Diacetylbenzene (DAB) is a metabolite of 1,2-diethylbenzene, which is commonly used in the manufacture of plastics and gasoline. We examined the neurotoxic effects of DAB in young and old rats, particularly its effects on hippocampus. Previously, we reported DAB impairs hippocampal neurogenesis but that the underlying mechanism remained unclear. In this study, we evaluate the toxicities exhibited by DAB in the hippocampi of 6-month-old (young) and 20-month-old (old) male SD rats by treating animals intraperitoneally with DAB at 3 mg/kg/day for 1 week. Hippocampal areas were dissected from brains and RNA was extracted and subjected to RNA-seq analysis. RNA results showed animals exhibited age-dependent sensitivity to the neurotoxic effects of DAB. We observed that inflammatory pathways were up-regulated in old rats but that metabolism- and detoxification-related pathways were up-regulated in young rats. This result in old rats, especially upregulation of the TREM1 signaling pathway (an inflammatory response involved in Alzheimer's disease (AD)) was confirmed by RT-PCR. Our study results provide a better understanding of age-dependent responses to DAB and new insight into the association between DAB and AD.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.4
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• pp.407-413
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• 2017

Vascular reactivity can be influenced by the vascular region, animal age, and pathologies present. Prostaglandins (produced by COX-1 and COX-2) play an important role in the contractile response to phenylephrine in the abdominal aorta of young rats. Although these COXs are found in many tissues, their distribution and role in vascular reactivity are not clear. At a vascular level, they take part in the homeostasis functions involved in many physiological and pathologic processes (e.g., arterial pressure and inflammatory processes). The aim of this study was to analyze changes in the contractile response to phenylephrine of thoracic/abdominal aorta and the coronary artery during aging in rats. Three groups of rats were formed and sacrificed at three distinct ages: prepubescent, young and old adult. The results suggest that there is a higher participation of prostanoids in the contractile effect of phenylephrine in pre-pubescent rats, and a lower participation of the same in old rats. Contrarily, there seems to be a higher participation of prostanoids in the contractile response of the coronary artery of older than pre-pubescent rats. Considering that the changes in the expression of COX-2 were similar for the three age groups and the two tissues tested, and that expression of COX-1 is apparently greater in older rats, COX-1 and COX-2 may lose functionality in relation to their corresponding receptors during aging in rats.

• Journal of Haehwa Medicine
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• v.8 no.1
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• pp.593-623
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• 1999

This experimental study was designed to verify the anti-aging efficacy of Eukmigihwangtang (EMGHT) and Rehmannia Radix, and determine the specific role and actions of Rehmannia Radix. Normal rat (2 months old), aging rat (8 months old), and pathologically induced rat (2 months old, injected 30mg/kg of streptozotocin) are observed to study the aging eliciting factors such as peroxide contents and enzyme activities. The following results were obtained in this study: 1. For the body weight changes, normal group given Rehmannia Radix showed decrease in the body weight compared to the control group, aging group given EMGHT and Rehmannia Radix showed significant decrease in the body weight, and STZ injected group showed suppression to the body weight loss when given EMGHT and Rehmannia Radix. 2. For the content changes in serum lipid peroxide, normal group showed increasing level as the rat gets older. Aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant decrease in the lipid peroxide level compared to the control group. Decrease was more prominant in the group given EMGHT. 3. For the changes in serum hydroxyl radical, normal group did not show significant changes, but aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant decrease in the hydroxyl radical level compared to the control group. Decrease was more prominant in the group given EMGHT. 4. For the changes in serum superoxide dismutase (SOD) activity, normal group did not show significant changes, but aging group given EMGHT and Rehmannia Radix showed significant increase in the SOD activity compared to the control group. STZ injected group given EMGHT and Rehmannia Radix showed significant decrease in the SOD activity compared to the control group. 5. For the content changes in hepatic lipid peroxide, aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant decrease in the lipid peroxide level compared to the control group. 6. For the changes in hepatic cytochrome P-450 activity, aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant decrease compared to the control group. Cytochrome b5 activity was significantly decreased only in the STZ injected group given EMGHT and Rehmannia Radix. 7. For the changes in hepatic aminopyrine demethylase and aniline hydroxylase activity, aging group given EMGHT and Rehmannia Radix showed significant decrease compared to the control group. STZ injected group given EMGHT and Rehmannia Radix showed significant increase in the aminopyrine demethylase activity, and showed significant decrease in the aniline hydroxylase activity compared to the control group. 8. For the content changes in hepatic protein bound-SH and nonprotein bound-SH, againg group and STZ injected group given EMGHT and Rehmannia Radix showed significant increase compared to the control group. 9. For the content changes in hepatic glutathione level, aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant increase compared to the control group. 10. For the changes in hepatic glutathione S-transferase activity, aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant increase and decrease, respectively, compared to the control group. 11. For the changes in hepatic glutathione reductase activity, aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant increase compared to the control group, while $\gamma$-Glutamylcystein synthetase activity did not show significant changes. 12. For the changes in hepatic superoxide dismutase activity, aging group and STZ injected group given EMGHT and Rehmannia Radix showed significant decrease compared to the control group. From the above results, the antioxidant effects of EMGHT and Rehmannia Radix were proved, as well as the role of Rehmannia Radix, a chief of EMGHT, was examined. In addition, since no change was reconized as the quantity of Rehmannia Radix and the order herbs increased, the reasonableness on EMGHT was proven with respect to its composition and quantity. Thus, the significance of EMGHT could be objectively exmined in terms of its composition and quantity. Considering animals used in the experiment, there were obvious changes in aging rats and pathologically induced rats than in normal rats. Consequently, it was noticeable that EMGHT and Rehmannia Radix were working selectively on the subjects.

• Journal of Life Science
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• v.21 no.10
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• pp.1415-1421
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• 2011

The purpose of this study was to identify the effects of an L-arginine supplementation and regular exercise training on NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1, eNOS and Ang II in the aortas of D-galactose (D-gal) induced aging rats. The male Strague-Dawley rats were treated with a D-galactose aging inducing agent; the D-gal injection (50 mg/kg) was given intraperitoneally for 12 wk. Experimental groups were divided into five groups: (1) Young control group (Y-Con, n=8), (2) Aging control group (A-Con, n=8), (3) Aging exercise group (A-Ex, n=8), (4) Aging exercise group with L-arginine supplementation group (A-Ex+A, n=8), and (5) Aging with L-arginine supplementation group (A-A, n=8). The exercise consisted of running on a treadmill for 60 min/day at 20 m/min for 6 day/wk, at 0% gradient for 12 wk. The L-arginine supplementation was given orally at a dose of 150 mg/kg/day for 12 wk. The findings of this study were as follows: 1. NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1 and Ang II proteins in the aortas of D-gal induced rats were significantly increased, however, L-arginine supplementation and regular exercise resulted in a significant inhibition in the expression of NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1 and Ang II proteins. 2. eNOS protein in the aortas of D-gal induced rats was significantly decreased, however, L-arginine supplementation and regular exercise resulted in a significant increase in the expression of eNOS proteins. In conclusion, the findings of the present study reveal that L-arginine supplementation alone or regular exercise alone or in combination with L-arginine supplementation for 12 wk increases anti-inflammatory effects by decreasing NF-${\kappa}B$, TNF-${\alpha}$, and iNOS protein expressions within the aortic tissue. In addition, L-arginine supplementation alone or regular exercise alone or in combination with L-arginine supplementation may prevent endothelial function by up-regulation of eNOS protein in the aortas of D-gal induced aging rats.

• Korean Journal of Medicinal Crop Science
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• v.14 no.6
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• pp.329-335
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• 2006

The present study was designed to investigate aging-related effects on the activities of xenobiotic metabolizing enzymes of rat liver by dietary supplementation of Korean red ginseng water-extract. Rat did not show any discernible signs of the rejection symptoms, and blood GOT and GPT levels were not influenced by ginseng water extracts, Cytochrome 450 levels and NADPH cytochrome P45O reductase, p-450 dependent ethoxycoumarin O-deethylase, and benzphetamine N-demethylase activities were decreased with aging, however, these phase I system enzymes activities in the ginseng group of24 months were well maintained compared with normal group. But, Levels of cytochrome bs and NADH-cytochrome b$_5$ reductase activities were also decreased with aging and were not found a clear difference between two groups. Glutathione-s-transferase activity, phase II enzyme system, in liver cytosols was also decreased in old ages, but the degree of decrease was higher in normal group than in giuseng supplemented group. These results indicate that long-term supplementation of red ginseng water extracts from weaning to 24 months do not show any side effects to rats, and retard age-related deteriorations of xenobiotic metabolizing enzymes activities in old ages.

• Journal of Nutrition and Health
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• v.20 no.2
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• pp.135-144
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• 1987

This study was carried out to investigate the effect of dietray carbohydrate level on the lipid and Ca metabolism, and on immune response in the process of aging. Sprag\ulcornerue - Dawley male rats of 12 months of age were fed either high carbohydrate or low carbohydrate diet for 9 months. With increasing age from 12 months to 21 months, there was no significant increase in body weight, however, the epididymal fat pat weight and total serum lipid tend to become higher, and the inorganic/organic matterratio in bone tends to become lower. This suggests that body fat accumulation increase and bone mass decrease with age. Rats fed low carbohydrate diet showed the higher epididymal fat pat weight, and the lower Ca content in femur and scapular compared to high carbohydrate diet fed rats. The immune response was also lower in low carbohydrate diet group judged by the lower thymus and spleen index and by the lower response to PHA and ConA stimulation. The results of this study suggests that the dietary level of carbohydrate and fat may play an important role in the process of aging. It could be recommended to practice high carbohydrate -low fat diet for the elderly to reduce the risk of degenerative diseases.

• Journal of Society of Preventive Korean Medicine
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• v.9 no.1
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• pp.49-63
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• 2005

Objectives : Ojayeonjonghwan(五子衍宗丸) is composed of Polygonum multiflorum THUNB, and some medical herbs that are known as formula of senescence delay effects. The purpose of this study is to investigate th effect of Ojayeonjonghwan on antioxidant enzyme activities, such as Thiobarbituric acid reactive substance(TBARS), Superoxide dismutase(SOD), Catalase(CAT), Glutathione preoxidase (GSH-px) in rat erythrocytes and blood plasma. Methods : Sprague-Dawley rats were divided into 3 groups, Normal group (supplied enough water and feeds only, Normal Group), D-galatose administered group(injected D-galatose 50mg/kg, 1time/day for 6 weeks, Control Group) and Ojayeonjonghwan administered group (D-galactose 50mg/kg and Ojayeonjonghwan extracts 245.0mg/200g 1time/day for 6 weeks, OJY Group). Rats were sacrificed and TBARS, SOD, CAT, GSH-px, Plasma total lipid, Plasma triglyceride and cholesterol were measured in rat erythrocytes and blood plasma. Results : TBARS in plasma concentration of OJY group was significantly lower than that of control group. Red blood cell(RBC) SOD activity of OJY group was significantly higher than that of control group(F=16.057, p=0.0001, ANOVA test), RBC GSH-px activity of OJY group was increased(F=4.271, p=0.034, ANOVA test). RBC catalase activities of all experimental group were not significantly different. Total lipid and triglyceride concentration in plasma of all experimental groups were not significantly different. Total cholesterol concentrations in plasma of OJY group were significantly lower than those of control group(F=4.387, p=0.032, ANOVA test). Conclusions : According to the above results, it is considered that Ojayeonjonghwan is effective in inhibiting lipid peroxidation and increasing antioxidative enzyme activities in D-galactose induced aging rat.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.1
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• pp.135-140
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• 2004

Anti-skin aging agent could be have an inhibition effect of ROS production as well as fragmentation and change of collagen cross linkage in collagen molecule. For the monitoring of lipid peroxidation and collagen degradation, the skin of young and old rats were incised and observed 7 days. In the result, the wound closure was observed in the skin from 10 of 11 young rats and in 8 of 11 old rats. And the longer wound length but shorter wound closure, weaker collagen density and thicker epidermis were observed in old rats than in young rats. The level of hydroxyproline as a parameter of collagen synthesis and MDA as a parameter of lipid peroxidation was lower in old group than in young group. The cyst and lacuna between collagen bundle and fibroblast were observed in old rats in contrast to young rats. So that we propose that MDA and hydroxyproline could be used for monitoring of anti-skin aging agent.

• Journal of Nutrition and Health
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• v.37 no.7
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• pp.525-532
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• 2004

This study was performed to investigate the age-related changes of the lipid metabolism and thrombogenic capacity in Sprague-Dawley (SD) rats at the ages of 4, 8, 12, 16, 20 and 24 months old. Total lipid, triglyceride (TG) and total cholesterol in plasma and liver, HDL-cholesterol concentration, and eicosanoid contents in plasma were measured. Lipid peroxides were determined by the levels of thiobarbituric acid reactive substance (TBARS) in LDL fraction. Body weight was increased continuous until 16 months and decreased after 20 months. Epididymal fat pad (EFP) weight was increased continuously until 20 months and decreased at 24 months. Total lipid and TG concentrations in plasma were increased until 20 months and then rapidly decreased at 24 months but plasma cholesterol was increased continuously with aging. HDL-cholesterol level was increased continuously until 12 months, but decreased at 16 months and maintained there after. The TBARS levels in LDL fraction were the highest level at 24 months. Liver total lipid, TG, and total cholesterol concentrations were shown a tendency to increase with aging, and especially TG concentration was increased rapidly from 12 months to 16 months. Plasma thromboxane B$_2$ (TXB$_2$) and 6-keto-prostaglandin F$_1$ (6-keto-PGF$_1$) contents did not change with aging, but the ratio of TXB$_2$/6-keto-PGF$_1$ was increased with aging, especially from 8 to 12 months. These results showed that lipid levels in plasma and liver, TBARS levels in LDL fraction, and TXB$_2$/6-keto-PGF$_1$ ratio were increased with aging.