• Journal of Ginseng Research
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• v.33 no.3
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• pp.177-182
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• 2009

Macrophages play an important role in the first line of immunologic effects against tumor cells. The effects of nonsaponin red ginseng (NSRG) components on macrophage functions like tumoricidal activity, phagocytic activity, and NO production in young (8-weeks-old) and aged (82-weeks-old) male C57BL/6 mice were assessed in vitro, respectively. The treatment of tumor cells (melanoma B16 cells) with the supernatants of NSRG-treated macrophages resulted in an increase of cytotoxicity at 300 $\mu$g/ml in the aged mice, whereas the supernatants did not have a cytotoxic effect in the young mice. It was observed that the supernatants induced the increase of tumor cell proliferation at 150 $\mu$g/ml in the young mice, suggesting that the supernatants contain growth factors rather than cytotoxic molecules. In addition, NSRG alone had a direct cytotoxic effect on the B16 tumor cells. NSRG had no effect on the NO production by the macrophages in the young mice, while it significantly increased the level of NO release in the aged mice. There was no difference in the phagocytic activities of the macrophages by NSRG in both groups of mice. These results suggest that NSRG has differential effects on the macrophage functions in young and aged mice.

• Parasites, Hosts and Diseases
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• v.51 no.3
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• pp.289-295
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• 2013

Different functions have been attributed to $CD4^+CD25^+Foxp3^+$ regulatory T-cells (Tregs) during malaria infection. Herein, we describe the disparity in Treg response and pro- and anti-inflammatory cytokines during infection with Plasmodium berghei ANKA between young (3-week-old) and middle-aged (8-month-old) C57BL/6 mice. Young mice were susceptible to cerebral malaria (CM), while the middle-aged mice were resistant to CM and succumbed to hyperparasitemia and severe anemia. The levels of pro-inflammatory cytokines, such as TNF-${\alpha}$, in young CM-susceptible mice were markedly higher than in middle-aged CM-resistant mice. An increased absolute number of Tregs 3-5 days post-inoculation, co-occurring with elevated IL-10 levels, was observed in middle-aged CM-resistant mice but not in young CM-susceptible mice. Our findings suggest that Treg proliferation might be associated with the suppression of excessive pro-inflammatory Th1 response during early malaria infection, leading to resistance to CM in the middle-aged mice, possibly in an IL-10-dependent manner.

• Nutrition Research and Practice
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• v.18 no.1
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• pp.46-61
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• 2024

BACKGROUND/OBJECTIVES: An increasing life expectancy in society has burdened healthcare systems substantially because of the rising prevalence of age-related metabolic diseases. This study compared the effects of animal protein hydrolysate (APH) and casein on metabolic diseases using aged mice. MATERIALS/METHODS: Eight-week-old and 50-week-old C57BL/6J mice were used as the non-aged (YC group) and aged controls (NC group), respectively. The aged mice were divided randomly into 3 groups (NC, low-APH [LP], and high-APH [HP] and fed each experimental diet for 12 weeks. In the LP and HP groups, casein in the AIN-93G diet was substituted with 16 kcal% and 24 kcal% APH, respectively. The mice were sacrificed when they were 63-week-old, and plasma and hepatic lipid, white adipose tissue weight, hepatic glucose, lipid, and antioxidant enzyme activities, immunohistochemistry staining, and mRNA expression related to the glucose metabolism on liver and muscle were analyzed. RESULTS: Supplementation of APH in aging mice resulted in a significant decrease in visceral fat (epididymal, perirenal, retroperitoneal, and mesenteric fat) compared to the negative control (NC) group. The intraperitoneal glucose tolerance test and area under the curve analysis revealed insulin resistance in the NC group, which was alleviated by APH supplementation. APH supplementation reduced hepatic gluconeogenesis and increased glucose utilization in the liver and muscle. Furthermore, APH supplementation improved hepatic steatosis by reducing the hepatic fatty acid and phosphatidate phosphatase activity while increasing the hepatic carnitine palmitoyltransferase activity. Furthermore, in the APH supplementation groups, the red blood cell (RBC) thiobarbituric acid reactive substances and hepatic H₂O₂ levels decreased, and the RBC glutathione, hepatic catalase, and glutathione peroxidase activities increased. CONCLUSIONS: APH supplementation reduced visceral fat accumulation and alleviated obesity-related metabolic diseases, including insulin resistance and hepatic steatosis, in aged mice. Therefore, high-quality animal protein APH that reduces the molecular weight and enhances the protein digestibility-corrected amino acid score has potential as a dietary supplement for healthy aging.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.83-90
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• 2017

Advanced age is one of the risk factors for vascular diseases that are mainly caused by impaired nitric oxide (NO) production. It has been demonstrated that endothelial arginase constrains the activity of endothelial nitric oxide synthase (eNOS) and limits NO generation. Hence, arginase inhibition is suggested to be vasoprotective in aging. In this study, we examined the effects of intravenous injection of Piceatannol, an arginase inhibitor, on aged mice. Our results show that Piceatannol administration reduced the blood pressure in aged mice by inhibiting arginase activity, which was associated with NO production and reactive oxygen species generation. In addition, Piceatannol administration recovered $Ca^{2+}$/calmodulin-dependent protein kinase II phosphorylation, eNOS phosphorylation and eNOS dimer stability in the aged mice. The improved NO signaling was shown to be effective in attenuating the phenylephrine-dependent contractile response and in enhancing the acetylcholine-dependent vasorelaxation response in aortic rings from the aged mice. These data suggest Piceatannol as a potential treatment for vascular disease.

• YAKHAK HOEJI
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• v.36 no.3
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• pp.269-277
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• 1992

The effects of ginseng saponins on the distribution of nerve cells in cerebral cortex of carbon monoxide (CO)-intoxicated mice were studied in the young ($5{\sim}8$ weeks) and aged ($43{\sim}52$ weeks) mice. Mice were exposed to 5000 ppm of CO for 40 minutes (72% HbCO). After that, nerve cells in motor(area 4), somatosensory(area 3) and visual(area 17) area of cerebral cortex was observed. In young mice, the number of nerve cells in each area was significantly decreased on 1st, 7th and 14th day after CO intoxication. In aged mice, that was also decreased after CO intoxication. Especially the number of the nerve cells in motor and somatosensory area was significantly decreased on 1st and 7th day, while that in visual area was decreased only on 1st day. The number of nerve cells in young mice pretreated with ginseng saponins were significantly decreased less on 7th and 14th day than that of untreated mice. The number of nerve cells in each area of normal aged mice was larger than that of normal young mice. The results suggest that CO exposure causes local degeneration or disturbance of nerve cells and delayed neurologic sequelae, while ginseng saponins might play a role of protective action on the nerve cells which were damaged by CO.

• Food Science and Biotechnology
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• v.14 no.6
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• pp.788-792
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• 2005

The effect of docosahexaenoic acid (DHA) on maze-learning ability in aged mice was investigated. Aged mice fed a diet deficient in n-3 fatty acid received a semi-purified diet of 0.5, 1 and 2% DHA-ethyl ester (DHA-EE) for 4 months. Maze-learning ability was assessed at 3 months after the start of the experiment. The time required to reach the maze exit and the number of times that a mouse strayed into blind alleys in the maze were measured in 3 trials conducted at 4-day intervals. The time was significantly less in the DHA-EE 0.5% and DHA-EE 2% groups than in the control group (p<0.05). The number of times mice strayed into blind alleys in the maze was significantly lower in the DHA-EE 2% group than in the control group (p<0.05). Mice fed DHA showed increased DHA and decreased level of arachidonic acid (AA) in the brain. These results suggest that the intake of a 2% DHA diet improves learning ability in aged mice, which is associated with a higher DHA content in the brain.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.717-725
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• 2021

Background: Korean Red Ginseng (KRG) is a traditional herb that has several beneficial properties including anti-aging, anti-inflammatory, and autophagy regulatory effects. However, the mechanisms of these effects are not well understood. In this report, the underlying mechanisms of anti-inflammatory and autophagy-promoting effects were investigated in aged mice treated with KRG-water extract (WE) over a long period. Methods: The mechanisms of anti-inflammatory and autophagy-promoting activities of KRG-WE were evaluated in kidney, lung, liver, stomach, and colon of aged mice using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR (qRT-PCR), and western blot analysis. Results: KRG-WE significantly suppressed the mRNA expression levels of inflammation-related genes such as interleukin (IL)-1β, IL-8, tumor necrosis factor (TNF)- α, monocyte chemoattractant protein-1 (MCP-1), and IL-6 in kidney, lung, liver, stomach, and colon of the aged mice. Furthermore, KRG-WE downregulated the expression of transcription factors and their protein levels associated with inflammation in lung and kidney of aged mice. KRG-WE also increased the expression of autophagy-related genes and their protein levels in colon, liver, and stomach. Conclusion: The results suggest that KRG can suppress inflammatory responses and recover autophagy activity in aged mice.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.95-101
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• 2014

Cardiovascular disease is the prime cause of morbidity and mortality and the population ages that may contribute to increase in the occurrence of cardiovascular disease. Arginase upregulation is associated with impaired endothelial function in aged vascular system and thus may contribute to cardiovascular disease. According to recent research, Korean Red Ginseng water extract (KRGE) may reduce cardiovascular disease risk by improving vascular system health. The purpose of this study was to examine mechanisms contributing to age-related vascular endothelial dysfunction and to determine whether KRGE improves these functions in aged mice. Young ($10{\pm}3$ weeks) and aged ($55{\pm}5$ weeks) male mice (C57BL/6J) were orally administered 0, 10, or 20 mg/mouse/day of KRGE for 4 weeks. Animals were sacrificed and the aortas were removed. Endothelial arginase activity, nitric oxide (NO) generation and reactive oxygen species (ROS) production, endothelial nitric oxide synthase (eNOS) coupling, vascular tension, and plasma peroxynitrite production were measured. KRGE attenuated arginase activity, restored nitric oxide (NO) generation, reduced ROS production, and enhanced eNOS coupling in aged mice. KRGE also improved vascular tension in aged vessels, as indicated by increased acetylcholine-induced vasorelaxation and improved phenylephrine-stimulated vasoconstriction. Furthermore, KRGE prevented plasma peroxynitrite formation in aged mice, indicating reduced lipid peroxidation. These results suggest KRGE exerts vasoprotective effects by inhibiting arginase activity and augmenting NO signaling and may be a useful treatment for age-dependent vascular diseases.

• Journal of Ginseng Research
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• v.39 no.4
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• pp.331-337
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• 2015

Background: The biological actions of various ginseng extracts have been studied for treating obesity and diabetes mellitus. However, few studies have evaluated the effects of fermented Korean Red Ginseng (Panax ginseng Meyer) on metabolic syndrome. The present study evaluated the antiobesity and antidiabetic effects of fermented red ginseng (FRG) on old-aged, obese, leptin-deficient (B6.V-Lepob, "ob/ob") mice. Methods: The animals were divided into three groups and given water containing 0%, 0.5%, and 1.0% FRG for 16 wk. The effect of FRG on ob/ob mice was determined by measuring changes in body weight, levels of blood glucose, serum contents of triglycerides, total cholesterol and free fatty acids, messenger RNA (mRNA) expressions of key factors associated with insulin action, such as insulin receptor (IR), lipoprotein lipase (LPL), glucose transporter 1 and 4 (GLUT1 and GLUT4), peroxisome proliferators-activated receptor gamma ($PPAR-{\gamma}$), and phosphoenolpyruvate carboxykinase (PEPCK) in the liver and in muscle, and histology of the liver and pancreas. Results: FRG-treated mice had decreased body weight and blood glucose levels compared with control ob/ob mice. However, anti-obesity effect of FRG was not evident rather than hypoglycemic effect in old aged ob/ob mice. The hyperlipidemia in control group was attenuated in FRG-treated ob/ob mice. The mRNA expressions of IR, LPL, GLUT1, GLUT4, $PPAR-{\gamma}$, and PEPCK in the liver and in muscle were increased in the FRG-treated groups compared with the control group. Conclusion: These results suggest that FRG may play a vital role in improving insulin sensitivity relative to reducing body weight in old-aged ob/ob mice.

• Preventive Nutrition and Food Science
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• v.15 no.1
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• pp.19-23
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• 2010

This study examined the effects of Acrylamide (ACR) and L-ascorbic acid (AsA) on the proliferation of splenocytes and the mitogen-stimulated lymphocyte proliferation in young (8 weeks) and aged (82 weeks) C57BL/6male mice in vitro. AsA increased splenocyte proliferation in both groups; however, this effect was higher in old mice, while the proliferation of lymphocyte was decreased except for treatment at $1\;{\mu}g/mL$ low concentration in both mice. In addition, ACR treatment resulted in decreased LPS-induced B lymphocyte proliferation and ConA-induced T lymphocyte proliferation in both groups. However, AsA increased LPS/ConA-induced lymphocyte proliferation in young groups and had no effects in old mice except at $0.5\;{\mu}g/mL$ Thus, the present data indicate that there is no difference effect of ACR and AsA on lymphocyte proliferation, whereas the effect of AsA on mitogen-induced cell proliferation was reduced in old mice. Overall, our results suggest that various immunomodulators have differing effects of lymphocytic proliferation on young versus aged mice.