• Natural Product Sciences
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• 제19권1호
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• pp.54-60
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• 2013

Rhus verniciflua Stokes (Anacadiaceae) is a plant that is native to East Asian countries, such as Korea, China, and Japan, and it has been found to exert various biological activities including antioxidative, anti-aggregatory, anti-inflammatory, anti-mutagenic, and apoptotic effects. Sulfuretin is one of the major flavonoid component isolated from the heartwood of R. verniciflua. Reactive oxygen species (ROS), produced via dental adhesive bleaching agents and pulpal disease, can cause oxidative stress. In the present study, we isolated sulfuretin from R. verniciflua and demonstrated that sulfuretin possesses cytoprotective effects against hydrogen peroxide ($H_2O_2$)-induced dental cell death. $H_2O_2$ is a representative ROS and causes cell death through necrosis in human dental pulp (HDP) cells. $H_2O_2$-induced cytotoxicity and production of ROS were blocked in the presence of sulfuretin, and these effects were dose dependent. Sulfuretin also increased heme oxygenase-1 (HO-1) protein expression. In addition, to determine whether sulfuretin-induced HO-1 expression mediated this cytoprotective effect, HDP cells were cotreated with sulfuretin in the absence or presence of SnPP, an inhibitor of HO activity. Sulfuretin-dependent HO-1 expression was required for suppression of $H_2O_2$-induced HDP cell death and ROS generation. These results indicate that sulfuretin-dependent HO-1 expression was required for the inhibition of $H_2O_2$-induced cell death and ROS generation. In addition, sulfuretin may be used to prevent functional dental cell death and thus may be useful as a pulpal disease agent.

• Bulletin of the Korean Chemical Society
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• 제30권4호
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• pp.897-901
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• 2009

Heme oxygenase-1 (HO-1) is an anti-inflammatory and anti-apoptotic protein and has been applied to various gene therapy researches. However, constitutive expression of HO-1 may induce deleterious side effects. In this research, hypoxia inducible HO-1 expression plasmid, pEpo-SV-HO-1, was constructed with the erythropoietin (epo) enhancer and simian virus 40 (SV40) promoter to avoid these unwanted side effects. Dexamethasone conjugated polyethylenimine (PEI-Dexa) was used as a gene carrier. It was previously reported that dexamethasone protected cardiomyocytes from apoptosis under hypoxia. In this research, PEI-Dexa reduced the caspase-3 level in hypoxic H9C2 cardiomyocytes as a derivative of dexamethasone, suggesting that PEI-Dexa is an anti-apoptotic reagent as well as a gene carrier. pEpo-SV-HO-1 was transfected to H9C2 cardiomyocytes using PEI-Dexa and the cells were incubated under normoxia or hypoxia. HO-1 expression was induced in the pEpo-SV-HO-1 transfected cells under hypoxia. In addition, cell viability under hypoxia was higher in the pEpo-SV-HO-1 transfected cells than the pEpo-SV-Luc transfected cells. Also, caspase-3 level was reduced in the pEpo-SV-HO-1 transfected cells under hypoxia. In addition to the anti-apoptotic effect of PEI-Dexa, hypoxia inducible HO-1 expression by pEpo-SVHO- 1 may be helpful to protect cardiomyocytes under hypoxia. Therefore, pEpo-SV-HO-1/PEI-Dexa complex may be useful for ischemic heart disease gene therapy.

• Anatomy and Cell Biology
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• 제50권3호
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• pp.207-213
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• 2017

Glycogen synthase kinase $(GSK)-3{\beta}$ and related enzymes are associated with various forms of neuroinflammation, including spinal cord injury (SCI). Our aim was to evaluate whether lithium, a non-selective inhibitor of $GSK-3{\beta}$, ameliorated SCI progression, and also to analyze whether lithium affected the expression levels of two representative $GSK-3{\beta}$-associated molecules, nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) (a target gene of Nrf-2). Intraperitoneal lithium chloride (80 mg/kg/day for 3 days) significantly improved locomotor function at 8 days post-injury (DPI); this was maintained until 14 DPI (P<0.05). Western blotting showed significantly increased phosphorylation of $GSK-3{\beta}$ (Ser9), Nrf-2, and the Nrf-2 target HO-1 in the spinal cords of lithium-treated animals. Fewer neuropathological changes (e.g., hemorrhage, inflammatory cell infiltration, and tissue loss) were observed in the spinal cords of the lithium-treated group compared with the vehicle-treated group. Microglial activation (evaluated by measuring the immunoreactivity of ionized calcium-binding protein-1) was also significantly reduced in the lithium-treated group. These findings suggest that $GSK-3{\beta}$ becomes activated after SCI, and that a non-specific enzyme inhibitor, lithium, ameliorates rat SCI by increasing phosphorylation of $GSK-3{\beta}$ and the associated molecules Nrf-2 and HO-1.

• The Korean Journal of Physiology and Pharmacology
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• 제23권2호
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• pp.121-130
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• 2019

Glutamate toxicity-mediated mitochondrial dysfunction and neuronal cell death are involved in the pathogenesis of several neurodegenerative diseases as well as acute brain ischemia/stroke. In this study, we investigated the neuroprotective mechanism of dieckol (DEK), one of the phlorotannins isolated from the marine brown alga Ecklonia cava, against glutamate toxicity. Primary cortical neurons ($100{\mu}M$, 24 h) and HT22 neurons (5 mM, 12 h) were stimulated with glutamate to induce glutamate toxic condition. The results demonstrated that DEK treatment significantly increased cell viability in a dose-dependent manner ($1-50{\mu}M$) and recovered morphological deterioration in glutamate-stimulated neurons. In addition, DEK strongly attenuated intracellular reactive oxygen species (ROS) levels, mitochondrial overload of $Ca^{2+}$ and ROS, mitochondrial membrane potential (${\Delta}{\Psi}_m$) disruption, adenine triphosphate depletion. DEK showed free radical scavenging activity in the cell-free system. Furthermore, DEK enhanced protein expression of heme oxygenase-1 (HO-1), an important anti-oxidant enzyme, via the nuclear translocation of nuclear factor-like 2 (Nrf2). Taken together, we conclude that DEK exerts neuroprotective activities against glutamate toxicity through its direct free radical scavenging property and the Nrf-2/HO-1 pathway activation.

• Biomolecules & Therapeutics
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• 제27권2호
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• pp.222-230
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• 2019

Intestinal barrier dysfunction always accompanies cirrhosis in patients with advanced liver disease and is an important contributor facilitating bacterial translocation (BT), which has been involved in the pathogenesis of cirrhosis and its complications. Several studies have demonstrated the protective effect of Vitamin D on intestinal barrier function. However, severe cholestasis leads to vitamin D depletion. This study was designed to test whether vitamin D therapy improves intestinal dysfunction in cirrhosis. Rats were subcutaneously injected with 50% sterile $CCl_4$ (a mixture of pure $CCl_4$ and olive oil, 0.3 mL/100 g) twice a week for 6 weeks. Next, $1,25(OH)_2D_3$ ($0.5{\mu}g/100g$) and the vehicle were administered simultaneously with $CCl_4$ to compare the extent of intestinal histologic damage, tight junction protein expression, intestinal barrier function, BT, intestinal proliferation, apoptosis, and enterocyte turnover. Intestinal heme oxygenase-1 (HO-1) expression and oxidative stress were also assessed. We found that vitamin D could maintain intestinal epithelial proliferation and turnover, inhibit intestinal epithelial apoptosis, alleviate structural damage, and prevent BT and intestinal barrier dysfunction. These were achieved partly through restoration of HO-1 and inhibition of oxidative stress. Taken together, our results suggest that vitamin D ameliorated intestinal epithelial turnover and improved the integrity and function of intestinal barrier in $CCl_4$-induced liver cirrhotic rats. HO-1 signaling activation was involved in these above beneficial effects.

• 한국축산식품학회지
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• 제32권3호
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• pp.339-345
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• 2012

분만 후 3일 이내에 분비되는 임실 지역의 젖소 초유에서 유청 단백질을 효율적으로 분리하고 RAW 264.7 세포의 증식 및 면역활성에 미치는 영향을 조사하였다. 실험에 사용한 초유의 유청 단백질 g당 TGF-${\beta}1$은 875 pg/mL,TGF-${\beta}2$는 6,600 pg/mL이었으며 실험에 사용한 초유 유청 단백질 내 총 TGF-${\beta}$의 양은 7,475 pg/mL이었다. RAW264.7 세포에 대한 초유 유청 단백질 첨가에 따른 세포증식 정도를 알아본 결과 10 mg/mL의 농도까지는 세포성장을 유도하였으나 20 mg/mL 이상의 농도에서는 세포성장을 억제하였다. 이에 RAW 264.7 세포에서의 초유 유청 단백질의 면역관련 실험에 사용할 농도는 최대 10 mg/mL까지로 결정하였다. RAW 264.7 세포에 초유 유청 단백질(0-10 mg/mL)과 LPS(1 ${\mu}g/mL$)를 차례로 반응시키고 NO생성량을 측정한 결과 초유 유청 단백질이 농도 의존적으로 NO의 생성을 억제하였다. 또한 LPS 자극에 의한 염증성 사이토카인(TNF-${\alpha}$, IL-$1{\beta}$, IL-6)이 생성되는 과정에서 초유 유청 단백질의 효과를 확인하였다. 그 결과, LPS를 단독으로 첨가했을 때 TNF-${\alpha}$, IL-$1{\beta}$, IL-6의 농도가 모두 증가하였으나 초유 유청 단백질을 첨가한 경우에는 염증성 사이토카인의 생성이 농도 의존적으로 감소하는 경향을 보였다. 초유 유청 단백질에 의해 NO를 비롯한 염증성 사이토카인의 생성이 억제되는 것이 heme oxygenase-1의 발현과 관련하는지 알아보고자 초유 유청 단백질을 농도별(0-10 mg/mL)로 처리하여 heme oxygenase-1의 발현여부를 측정한 결과 대조군과 비교하여 3-4배 이상의 발현 증가를 보였다. 이상의 결과들로 미루어보아 LPS로 자극된 RAW 264.7 세포에서 TGF-${\beta}$ 등을 함유한 초유 유청 단백질은 10 mg/mL 이하의 농도에서 농도 의존적으로heme oxygenase-1의 발현을 유도하여 염증성 사이토카인인 TNF-${\alpha}$, IL-$1{\beta}$, IL-6 및 NO의 생성을 억제하는 것으로 판단되었다.

• Journal of Nutrition and Health
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• 제27권5호
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• pp.451-459
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• 1994

This study was performed to investigate the effect of sources of protein on iron bioavailability in 10 healthy young Korean women. The 18-day metabolic study consisted of a 6-day adaptation period, 6-day moderate protein(60g protein/day, 18mg Fe/day) and 6-day high protein period(90g protein/day, 18mg Fe/day). During the moderate and high protein period, 5 subjects were fed the high plant protein meals(80% plant protein). Fecal excretion of dietary iron was significantly higher(p<0.05) in high protein high plant diet group(HPP, 9.48$\pm$1.61mg/day) than in high protein high animal diet group (HPA, 14.40$\pm$0.89mg/day). Apparent absorption and bioavailability of iron was also significantly higher(p<0.10) in HPA(40.7$\pm$5.3%, 6.46$\pm$1.61mg/day) than in HPP(14.4$\pm$5.3%, 2.39$\pm$0.89mg/day). But there was no significant difference between the high animal protein group and high plant protein group in moderate protein period. Serum iron concentration and transferrin saturation increased as animal protein intake increased, from 106.0$\pm$5.1ug/이 and 30.6$\pm$1.5% for MPA to 129.1$\pm$6.7ug/이 and 37.1$\pm$1.3% for HPA. Statistically positive correlations were shown not only between the level of dietary heme iron and apparent absorption(r=0.95, p<0.05), but also between serum iron concentration and apparent absorption(r=0.64, p<0.05). Negative iron balance was shown in two subjects fed the moderate protein meals. These results suggest that recommanded dietary allowances of iron may be under the need to maintain the positive balance, and iron bioavaliability increase by only high level of animal protein intake.

• Toxicological Research
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• 제20권4호
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• pp.293-298
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• 2004

Background: Crohn's disease is characterized by a chronic relapsing inflammation of the bowel. Gliotoxin has been known to play strong immunosuppressive properties, while mechanisms for its anti-inflammatory actions are not completely understood. Here, we investigated the effects of gliotoxin in trinitrobenzene sulfonic acid (TNBS) induced mouse colitis, an animal model of Crohn's disease. Results: Gliotoxin dramatically improved clinical and histopathological symptoms in accompanied with reduced expression of TNF-$\alpha$, IL-1$\beta$, and ICAM-1 protein levels in TNBS induced colitis. Interestingly Gliotoxin induced Heme oxygenase-1 (HO-1) and the HO-1 inducer cobalt protoporphyrin IX (CoPPIX) completely mimicked the protective effects of gliotoxin in TNBS induced colitis mice. In contrast, the HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX) could reverse the anti-inflammatory effects of gliotoxin and CoPPIX. Conclusions: Gliotoxin is a potential therapeutic agent targeting for the treatment of Crohn's disease by inducing HO-1.

• Food Science and Biotechnology
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• 제18권5호
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• pp.1055-1062
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• 2009

This study was conducted to investigate whether dietary chlorella intake could have an effect on antioxidative capacity in rats oxidatively stressed with cadmium (Cd). Sprague-Dawley rats fed dietary chlorella (0, 5, and 10%) for 4 weeks after induction of oxidative stress by exposing to Cd (200 ppm) for 8 weeks. After the oxidative stress applied, plasma and liver malondialdehyde concentrations and xanthine oxidase activities were decreased in 5% chlorella fed group compared to chlorella free group. Although liver heme oxygenase-1 protein expression was not affected by chlorella, the enzyme activity was improved in 5% chlorella fed group. Erythrocyte superoxide dismutase activity and hepatic metallothionein concentration were increased in 5% chlorella fed group. However, 10% chlorella intake had no effect on the improvement of oxidative stress-related enzymes and proteins. These findings suggest that, after induction of oxidative stress with Cd, 5% chlorella intake might improve antioxidative capacity against oxidative stress.

• 한국식품과학회지
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• 제52권3호
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• pp.244-248
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• 2020

To retain valuable resources, organisms adopt several strategies including coprophagy. Cells covering the outer skin and internal digestive lumen are actively recycled to maintain their integrity. In present study, we suggested that the small intestine can consume dead cells in a manner similar to how it consumes protein from the diet. We examined the eluates from five segments of the mouse small intestine and cecum and 2 segments of the large intestine and small intestine tissue, and detected immunoreactivity with eukaryotic caveolin-1 and β-actin antibodies only in the cecum and 2 segments from the large intestine. Bacterial agitation of the mouse intestine with Shigella disrupted the architecture and absorptive function of the small intestine. Small intestine eluates were immunoreactive with murine caveolin-1 and contained heme as determined by dot blot analysis. We concluded that the body conserves resources in the small intestine by disposing of and recycling shedded cells.