• Molecular Medicine Reports
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• v.20 no.5
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• pp.4111-4118
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• 2019

The administration of D-galactose triggers brain aging by poorly understood mechanisms. It is generally recognized that D-galactose induces oxidative stress or affects protein modifications via receptors for advanced glycated end products in a variety of species. In the present study, we aimed to investigate the involvement of astrocytes in D-galactose-induced brain aging in vitro. We found that D-galactose treatment significantly suppressed cell viability and induced cellular senescence. In addition, as of the accumulation of senescent cells, we proposed that the senescence-associated secretory phenotype (SASP) can stimulate age-related pathologies and chemoresistance in brain. Consistently, senescent astrocytic CRT cells induced by D-galactose exhibited increases in the levels of IL-6 and IL-8 via NF-κB activation, which are major SASP components and inflammatory cytokines. Conditioned medium prepared from senescent astrocytic CRT cells significantly promoted the viability of brain tumor cells (U373-MG and N2a). Importantly, conditioned medium greatly suppressed the cytotoxicity of U373-MG cells induced by temozolomide, and reduced the protein expression levels of neuron marker neuron-specific class III β-tubulin, but markedly increased the levels of c-Myc in N2a cells. Thus, our findings demonstrated that D-galactose treatment might mimic brain aging, and that D-galactose could contribute to brain inflammation and tumor progression through inducing the accumulation of senescent-secretory astrocytes.

• Journal of Pharmacopuncture
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• v.20 no.1
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• pp.29-35
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• 2017

Objectives: Aging is an unconscious and gradual process that can lead to changes in biological systems. Induction of oxidative stress and apoptosis, hepatotoxicity and neurotoxicity are involved in the aging process. Regarding the antioxidant property of black seed oil, the aim of this study was to evaluate the anti-aging effect of Nigella sativa (N. sativa) oil on d-galactose-induced aging in mice. Methods: For induction of aging, D-galactose (500 mg/kg, subcoutaneously SC) was administrated to male mice for 42 days. Animals were treated with D-galactose alone or with b lack seed oil (0.1, 0.2, 0.5 mL/kg, intraperitoneally (ip)). Additionally, vitamin E (200 mg/kg) was used as a positive control. At the end of treatment, the malondialdehyde (MDA) and the glutathione (GSH) contents in brain and liver tissues were measured. Also, enzymes in serum, including aspartate aminotransferase (AST) and alanine amino transferase (ALT), were determined. The levels of the proteins Bax, Bcl2, caspase-3 (pro and cleaved) in brain and liver tissues were evaluated. Results: Administration of D-galactose (500 mg/kg, SC) for 42 days increased serum levels of ALT and AST, as well as the MDA content, in brain and liver tissues, but decreased the GSH content. Additionally, the levels of apoptotic proteins, including Bax, procaspase-3 and caspase-3 cleaved, were markedly increased. N. sativa oil (0.1 and 0.2 mL/kg) diminished the levels of the biochemical markers ALT and AST. Administration of black seed oil (0.1, 0.2 and 0.5 mL/kg) reduced lipid peroxidation and at doses 0.1 and 0.2 mL/kg significantly recovered the GSH content. The oil decreased Bax/Bcl2 levels and at 0.1 mL/kg down-regulated the expressions of caspase-3 (pro and cleaved) proteins in brain and liver tissues. Conclusion: Through its antioxidant and anti-apoptosis properties, black seed oil exhibited an anti-aging effect in a model of aging induced with D-galactose.

• Nutrition Research and Practice
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• v.14 no.3
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• pp.188-202
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• 2020

BACKGROUND/OBJECTIVES: Brain aging is a major risk factor for severe neurodegenerative diseases. Conversely, L-histidine and L-carnosine are known to exhibit neuroprotective effects. The aim of this study was to examine the potential for L-histidine, L-carnosine, and their combination to mediate anti-brain aging effects in neuronal cells subjected to D-galactose-induced aging. MATERIALS/METHODS: The neuroprotective potential of L-histidine, L-carnosine, and their combination was examined in a retinoic acid-induced neuronal differentiated SH-SY5Y cell line exposed to D-galactose (200 mM) for 48 h. Neuronal cell proliferation, differentiation, and expression of anti-oxidant enzymes and apoptosis markers were subsequently evaluated. RESULTS: Treatment with L-histidine (1 mM), L-carnosine (10 mM), or both for 48 h efficiently improved the proliferation, neurogenesis, and senescence of D-galactose-treated SH-SY5Y cells. In addition, protein expression levels of both neuronal markers (β tubulin-III and neurofilament heavy protein) and anti-oxidant enzymes, glutathione peroxidase-1 and superoxide dismutase-1 were up-regulated. Conversely, protein expression levels of amyloid β (1-42) and cleaved caspase-3 were down-regulated. Levels of mRNA for the pro-inflammatory cytokines, interleukin (IL)-8, IL-1β, and tumor necrosis factor-α were also down-regulated. CONCLUSIONS: To the best of our knowledge, we provide the first evidence that L-histidine, L-carnosine, and their combination mediate anti-aging effects in a neuronal cell line subjected to D-galactose-induced aging. These results suggest the potential benefits of L-histidine and L-carnosine as anti-brain aging agents and they support further research of these amino acid molecules.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.2
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• pp.131-137
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• 2021

Aging is the process spontaneously occurred in living organisms. Cardiac fibrosis is a pathophysiological process of cardiac aging. Mangiferin is a well-known C-glucoside xanthone in mango leaves with lots of beneficial properties. In this study, rat model of cardiac fibrosis was induced by injected with 150 mg/kg/d D-galactose for 8 weeks. The age-related cardiac decline was estimated by detecting the relative weight of heart, the serum levels of cardiac injury indicators and the expression of hypertrophic biomakers. Cardiac oxidative stress and local inflammation were measured by detecting the levels of malondialdehyde, enzymatic antioxidant status and proinflammatory cytokines. Cardiac fibrosis was evaluated by observing collagen deposition via masson and sirius red staining, as well as by examining the expression of extracellular matrix proteins via Western blot analysis. The cardiac activity of profibrotic TGF-β1/p38/MK2 signaling pathway was assessed by measuring the expression of TGF-β1 and the phosphorylation levels of p38 and MK2. It was observed that mangiferin ameliorated D-galactose-induced cardiac aging, attenuated cardiac oxidative stress, inflammation and fibrosis, as well as inhibited the activation of TGF-β1/p38/MK2 signaling pathway. These results showed that mangiferin could ameliorate cardiac fibrosis in D-galactose-induced aging rats possibly via inhibiting TGF-β/p38/MK2 signaling pathway.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.224-230
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• 2011

In order to develop silk peptide (SP) preparations possessing cognition-enhancing effect, several candidates were screened through in vitro assays, and their effectiveness was investigated in facilitated brain aging model rats. Incubation of brain acetyl-cholinesterase with SP-PN (1-1,000 ${\mu}g/ml$) led to inhibition of the enzyme activity up to 35%, in contrast to a negligible effect of SP-NN. The expression of choline acetyltransferase (ChAT) mRNA of neural stem cells expressing ChAT gene (F3.ChAT) was increased by 24-hour treatment with 10 and 100 ${\mu}g/ml$ SP-NN (1.35 and 2.20 folds) and SP-PN (2.40 and 1.34 folds). Four-week subcutaneous injections with D-galactose (150 mg/kg) increased activated hippocampal astrocytes to 1.7 folds (a marker of brain injury and aging), decreased acetylcholine concentration in cerebrospinal fluid by 45-50%, and thereby impaired learning and memory function in passive avoidance and water-maze performances. Oral treatment with SP preparations (50 or 300 mg/kg) for 5 weeks from 1 week prior to D-galactose injection exerted recovering activities on acetylcholine depletion and brain injury/aging as well as cognitive deficit induced by D-galactose. The results indicate that SP preparations restore cognitive functions of facilitated brain aging model rats by increasing the release of acetylcholine, in addition to neuroprotective activity.

• 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.

• International Journal of Industrial Entomology and Biomaterials
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• v.23 no.2
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• pp.201-206
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• 2011

Using proteases, we produced a peptide mixture from fibroin of the silkworm $Bombyx$ $mori$. Mice received D-galactose by subcutaneous injection for 8 weeks to accelerate aging, and then received the peptide mixture orally for 7 weeks. In the mice aged with D-galactose, the coefficient of friction of hair increased significantly up to 1.6-fold, but in the mice subsequently given the peptide mixture, it was normal. Scanning electron microscopy showed improved hair cuticles in the latter mice too. These results indicate that oral administration with peptides from $Bombyx$ fibroin counters the aging of hair cuticles.

• The Journal of Pediatrics of Korean Medicine
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• v.19 no.1
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• pp.153-171
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• 2005

Objective : This experiment has been done to evaluate the effects of Gamisogunjung-tang(GST) on antioxidant capability and lipidic concentration in blood which are presumed to be related to aging. Method : In this study, we divided 14 weeks old SD rats into normal group, control group and GST group. Control and GST group were induced aging by D-galactose. At the same time GST group were administered extract of Gamisogunjung-tang for 6 weeks. After then we took blood, and measured the activities of SOD, GSH-px, catalase in erythrocytes and measured TBARS values, concentrations of total lipid, tryglyceride, total cholesterol, HDL-cholesterol in plasma. Results : The activities of SOD, GSH-px, catalase in erythrocytes increased significantly in GST group compared with control group. The value of TBARS and the concentration of total lipid, total cholesterol in plasma decreased significantly in GST group compared with control group. The concentration of HDL-cholesterol increased significantly in GST group compared with control group. The concentration of triglyceride were not noticeable. Conclusion : it is considered that Gamisogunjung-tang has an influence on control aging by activation the antioxidative enzyme systems in erythrocytes and decreasing the concentration of lipid in blood plasma.

• Nutrition Research and Practice
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• v.16 no.1
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• pp.1-13
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• 2022

BACKGROUND/OBJECTIVES: Bitter taste receptors are taste signaling pathway mediators, and are also expressed and function in extra-gustatory organs. Skin aging affects the quality of life and may lead to medical issues. The purpose of this study was to better understand the anti-skin aging effects of bitter taste receptors in D-galactose (D-gal)-induced aged human keratinocytes, HaCaT cells. MATERIALS/METHODS: Expressions of bitter taste receptors in HaCaT cells and mouse skin tissues were examined by polymerase chain reaction assay. Bitter taste receptor was overexpressed in HaCaT cells, and D-gal was treated to induce aging. We examined the effects of bitter taste receptors on aging by using β-galactosidase assay, wound healing assay, and Western blot assay. RESULTS: TAS2R16 and TAS2R10 were expressed in HaCaT cells and were upregulated by D-gal treatment. TAS2R16 exerted protective effects against skin aging by regulating p53 and p21, antioxidant enzymes, the SIRT1/mechanistic target of rapamycin pathway, cell migration, and epithelial-mesenchymal transition markers. TAS2R10 was further examined to confirm a role of TAS2R16 in cellular senescence and wound healing in D-gal-induced aged HaCaT cells. CONCLUSIONS: Our results suggest a novel potential preventive role of these receptors on skin aging by regulating cellular senescence and wound healing in human keratinocyte, HaCaT.

• Journal of Society of Preventive Korean Medicine
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• v.8 no.1
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• pp.115-133
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• 2004

Hasuohwan(何首烏丸) composed of Polygonum multiflorum Thunb and some medical herbs are known as formula of senescence delay effect. The aim of this study is to investigate the effect of Hasuohwan(何首烏丸) on antioxidant enzyme activity such as Thiobarbituric acid reactive substance(TBARS) in rat plasma and liver, Superoxide dismutase(SOD), Glutathione peroxidase(GSH-px), Catalase(CAT) in rat erythrocyte and liver. Rats were sacrificed and TBARS was measured in rat plasma and liver. SOD, GSH-px and CAT were measured in rat erythrocytes and liver. TBARS in plasma concentrations of HSO group was significantly lower than those of control group. RBC and liver GSH-px activities of HSO group were significantly higher than those of control group. According to above results, it is considered that Hasuohwan is effective in inhibiting lipid peroxidation and increasing antioxidative enzyme activities in D-galactose induced aging rat. Therefore, Hsuohwan is considered in effective of senescence delay.