• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.4
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• pp.409-416
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• 2017

1,2,3,4,6-Penta-O-galloyl-${\beta}$-D-glucose (PGG) is a gallotannin isolated from Galla Rhois. In a previous study, PGG was shown to suppress the allergic response by attenuating immunoglobulin E production both in vitro and in vivo. However, the effect of PGG on bacteria-induced inflammation at physiological concentration remains unclear. Therefore, the aim of this study was to investigate the effect of PGG on lipopolysaccharide (LPS)-stimulated macrophages. PGG inhibited release of nitric oxide (NO) and prostaglandin $E_2$ by alleviating protein expression of inducible NO synthase and cyclooxygenase-2 in LPS-treated RAW264.7 cells. Furthermore, PGG suppressed the release of interleukin-6 and tumor necrosis factor-${\alpha}$ induced by LPS. Further study indicated that PGG blocked translocation of the p65 subunit of nuclear factor-${\kappa}B$ from the cytosol into the nucleus, which is one of the underlying mechanisms of the anti-inflammatory action of PGG. Collectively, these data suggest that PGG might be useful for the treatment of inflammatory disease.

• Journal of Periodontal and Implant Science
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• v.35 no.2
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• pp.345-357
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• 2005

Prostaglandin plays a significant role in the local control of bone metabolism associated with periodontal disease. ${\Delta}^{12}-PGJ_2$ is a natural $PGD_2$ metabolite that is formed in vivo in the presence of plasma. It is known for ${\Delta}^{12}-PGJ_2$ to stimulate calcification in osteoblastic cells. Bone morphogenetic protein(BMP) stimulated osteoblastic differentiation in various types of cells and greatly enhanced healing of bony defects. The purpose of this study was to evaluate the effect of rhEMP-2 on ${\Delta}^{12}-PGJ_2$ induced osteoblastic differentiation and mineralization in vitro. A human osteosarcoma cells line Saos-2 were cultured. In the test groups, 10-7M of ${\Delta}^{12}-PGJ_2$ or mixture of 10-8M of ${\Delta}^{12}-PGJ_2$ and 100ng/ml of rhBMP-2 or 100ng/ml of rhEMP-2 were added to culture media. After 1 day, 2 days and 4 days of culture period, the cell number was measured. Alkaline phosphatase activity was measure at 3 days. Reverse transcription polymerase chain reaction(RT-PCR) was performed to determine the expression of mRNA of bone matrix protein at 8 hours, 1 day and 7 days. The ability to produce mineralized nodules in rat osteoblasts(MC3T3-E1) was evaluated at 21 days. The results were as follows : 1. rhEMP-2 or mixture of rhBMP-2 and ${\Delta}^{12}-PGJ_2$ inhibited cell proliferation of human osteosarcoma cells. 2. rhEMP-2 or mixture of rhBMP-2 and ${\Delta}^{12}-PGJ_2$ stimulated alkaline phosphatase activity significantly higher than ${\Delta}^{12}-PGJ_2$ alone. 3. rhBMP-2 or mixture of rhEMP-2 and ${\Delta}^{12}-PGJ_2$ stimulated mineralization compared to ${\Delta}^{12}-PGJ_2$ alone. 4. mRNA of alkaline phosphatase, BMP-2, cbfa 1, Type I collagen were detected in the group treated with ${\Delta}^{12}-PGJ_2$/rhBMP-2, rhBMP-2 alone, ${\Delta}^{12}-PGJ_2$ alone. These results show that mixture of ${\Delta}^{12}-PGJ_2$ and rhBMP-2 causes more bone formation than ${\Delta}^{12}-PGJ_2$ alone while the bone formation effects of mixture of ${\Delta}^{12}-PGJ_2$ and rhBMP-2 are less than those of rhBMP-2 alone. Further researches would be necessary to clarify the interactions of these agents.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.685-696
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• 2021

In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.

• Fisheries and Aquatic Sciences
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• v.25 no.11
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• pp.579-586
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• 2022

Research on the potential biological activity of red alga Symphyocladia spp. has been limited to Symphyocladia latiuscula, which is widely used as a food ingredient in Korea. Here, we examined the biological activity of another species, Symphyocladia linearis, which is found in Korea and was reported as a new species in 2013. The aim of this study was to evaluate the antioxidant, anti-inflammatory, and antibacterial properties of a 70% ethanol extract of S. linearis. Antioxidant activity, which was evaluated using radical scavenging assays, revealed half maximal inhibitory concentration values for 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) of 34.57 and 11.70 ㎍/mL algal extract, respectively. Anti-inflammatory activity of the S. linearis ethanolic extract was evaluated using RAW 264.7 cells by measuring the inhibition of lipopolysaccharide-induced nitric oxide (NO) and prostaglandin E₂ (PGE₂) production. The potential cytotoxicity of NO and PGE₂ was first examined, confirming no toxicity at concentrations ranging from 10-100 ㎍/mL. NO production was inhibited 61.1% and 78.0% at 50 and 100 ㎍/mL S. linearis extract, respectively; and PGE₂ production was inhibited 69.1%, 83.2%, and 94.8% at 25, 50, and 100 ㎍/mL S. linearis extract, respectively. Thus, the S. linearis extract showed very strong efficacy against PGE₂ production. The cellular production of reactive oxygen species, measured using 2',7'-dichlorofluorescin diacetate fluorescence, was inhibited 48.8% by the addition of 100 ㎍/mL S. linearis extract. Antibacterial activity was evaluated using the disc diffusion method and minimum inhibitory concentration (MIC). S. linearis was effective only against gram-positive bacteria, exhibiting antibacterial activity against Staphylococcus aureus with a MIC of 256 ㎍/mL extract and against Bacillus cereus with a MIC of 1,024 ㎍/mL extract. Based on these results, we infer that a 70% ethanolic extract of S. linearis possesses strong anti-inflammatory properties, and therefore has the potential to be used in the prevention and treatment of inflammatory and immune diseases.

• Journal of Veterinary Science
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• v.24 no.6
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• pp.83.1-83.12
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• 2023

Background: Ellipticine (Ellip.) was recently reported to have beneficial effects on the differentiation of adipose-derived stem cells into mature chondrocyte-like cells. On the other hand, no practical results have been derived from the transplantation of bone marrow stem cells (BMSCs) in a rabbit osteoarthritis (OA) model. Objectives: This study examined whether autologous BMSCs incubated with ellipticine (Ellip.+BMSCs) could regenerate articular cartilage in rabbit OA, a model similar to degenerative arthritis in human beings. Methods: A portion of rabbit articular cartilage was surgically removed, and Ellip.+BMSCs were transplanted into the lesion area. After two and four weeks of treatment, the serum levels of proinflammatory cytokines, i.e., tumor necrosis factor α (TNF-α) and prostaglandin E2 (PGE2), were analyzed, while macroscopic and micro-computed tomography (CT) evaluations were conducted to determine the intensity of cartilage degeneration. Furthermore, immuno-blotting was performed to evaluate the mitogen-activated protein kinases, PI3K/Akt, and nuclear factor-κB (NF-κB) signaling in rabbit OA models. Histological staining was used to confirm the change in the pattern of collagen and proteoglycan in the articular cartilage matrix. Results: The transplantation of Ellip.+BMSCs elicited a chondroprotective effect by reducing the inflammatory factors (TNF-α, PGE2) in a time-dependent manner. Macroscopic observations, micro-CT, and histological staining revealed articular cartilage regeneration with the downregulation of matrix-metallo proteinases (MMPs), preventing articular cartilage degradation. Furthermore, histological observations confirmed a significant boost in the production of chondrocytes, collagen, and proteoglycan compared to the control group. Western blotting data revealed the downregulation of the p38, PI3K-Akt, and NF-κB inflammatory pathways to attenuate inflammation. Conclusions: The transplantation of Ellip.+BMSCs normalized the OA condition by boosting the recovery of degenerated articular cartilage and inhibiting the catabolic signaling pathway.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.39-45
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• 2023

Biorenovation is a biotransformation method that converts the structure of chemical compounds and natural product through biocatalytic metabolism of microorganism and could enhance biological effectiveness and mitigate cytotoxicity compared to its substrates. Althaea rosea L. has been used as oriental medicine and is known for physiological efficacies such as antiurolithiatic, anti-inflammatory, and anti-cancer activities. A. rosea L. callus, the plant tissue grown to protect its wound, has been reported to have antioxidant and whitening effects. However, mechanisms of its other activity such as inflammation have not yet been investigated. In this study, we extracted A. rosea L. callus (AR) and produced biorenovated AR (ARBR), and then analyzed anti-inflammatory effect in Lipopolysaccharide-induced RAW 264.7 macrophage at 50, 100, 200 ㎍/mL of ARBR. As a result of inhibition test of nitric oxide production, it was found that ARBR was superior to AR without apparent toxicity. Furthermore, ARBR significantly inhibited production of prostaglandin E₂, inducible nitric oxide synthase, cyclooxygenase-2 and pro-inflammatory cytokines including Tumor necrosis factor-α, Interleukin-6, Interleukin-1β in a concentration-dependent manner. In conclusion, we suggest that ARBR could regulate the excessive inflammatory response to an appropriate level and be a promising material for functional cosmetics and pharmaceuticals.

• Journal of Chest Surgery
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• v.30 no.10
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• pp.949-960
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• 1997

Background. Limited ischemic tolerance of the lung has remained one of the factors that limits the expansion of pulmonary transplantation as a treatment for end-stage pulmonary disease. Numerous studies on safe long term preservation for lung transplantation has been performed for the purpose of developing ideal preservation solution with extracellular type or intracellular type solutions. In this. study, we examined the efficacy of L DG solution in lung preservation longer than 20 hours by comparison with modified Euro-Collins solution. Iwethods. Thirty-(our adult mongrel dogs were divided into two groups. Donor lungs were flushed with LPDG solution(n=9) or modified Euro-Collins(MEC) solution(n=8) and stored for 24 hours at 1$0^{\circ}C$. All donor lungs were perfused through the pulmonary arteries with solutions containing prostaglandin El and verapamil. Left canine lung allotransplantations wereperformed. Assessment(hemodynamic indices and arterial blood gas analysis) of left implanted lung was made by occluding the right pulmonary artery for ten minutes using pulmonary artery Cuff. Assessment was repeated at the interval of 30 minutes, one hour, and two hours later after reperfusion and then chest X-ray, computed tomogram and lung perfusion scan were obtained. In survival dogs follow-up studies were done with assessment with chest X-ray, computed tomogram of the chest and lung perfusion scan on 7th day postoperatively. After preservation above 20 hours, pathological examinations for ultrastructural findings on right lung were performed in each group. Results. With respect to arterial oxygen tension, LPDG group was superior to MEC but there was no statistical significance for 2 hours after reperfusion. Mean pulmonary artery pressure was less increased(p < 0.05) and cardiac output higher(p <0.05) than MEC group until 2 hours after reperfusion. After 2 hours of reperfusion, both groups showed transplanted lung function deteriorated gradually. Perfusion scan of the transplanted lung in LPDG group showed better perfusion rate in immediate post-reperfusion, 3 days and 7 days later respectively but there was no statistical significance and corelation with PaO2 and computed tomoRravhic views. In scanning electron microscopy of pulmonary artery after preservation, LPDG group relatively shows less irregular protrusion of the inner surface of endothelial cell of poulmonary artery than MEC group. Conclusions, e concluded that LPDG solution can offer safe lung preservation above 20 hours with adequate immunosuppressive therapy and prevention of the infection.

• Tuberculosis and Respiratory Diseases
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• v.39 no.4
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• pp.304-309
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• 1992

Background: The alveolar macrophage may metabolize arachidonic acid through cyclooxygenase- and lipoxygenase- catalyzed pathways to produce a variety of metabolites of arachidonic acid. The production of these metabolites of arachidonic acid may enhance the defensive ability of the challenged lung. However, continued stimulation with the consequent production of proinflammtory metabolites of arachidonic acid, may ultimately enhance the disease process by contributing to chronic bronchoconstriction, fibrosis, and the persistent release of toxic oxygen species. Silicosis is an example of a disease process resulting from chronic exposure of the lung to foreign particles. This study was carried out to evaluate the changes of arachidonic acid metabolites from macrophages in experimental silicosis. Methods: We measured $PGE_2$, and $LTB_4$ in cultured macrophages taken from rats by radioimmunoassay at 24 and 48 hours after stimulation by silica dust, natural carbon dust, lipopolysaccharide, calcium ionophore (A23187) and medium (RPMI) as a control. For the experimental silicosis, 50 mg silica in 0.5 ml saline was administered intratracheally into the rat and grown to 20 weeks and measured $PGE_2$, and $LTB_4$ in the cultured macrophages lavaged from that rat. The used stimulants were the same as above. Results: 1) The amount of $PGE_2$ in the cultred macrophages from normal rat was significantly decreased in the group which was stimulated with silica dust for 48 hours compare with control non-stimulated group. 2) In the experimental silicosis group, $PGE_2$, release in cultured macrophages after 48 hours incubation with silica and natural carbon dust tended to be lower than those of non-stimulated group. 3) There were marked changes of $LTB_4$ in the groups of normal rats which were incubated with silica for 24, 48 hours and natural carbon for 48 hours compared with non-stimulated group. 4) In the experimental silicosis group, the release of $LTB_4$ was significantly increased macrophages cultured with silica and natural carbon dust after 24 and 48 hours incubation compared with non-stimulated group. Conclusion: The results of these studies suggest that the in vitro exposure of rat alveolar macrophge to silica and coal dust results in an alteration in alveolar macrophage metabolism of arachidonic acid that may promote an inflammatory reaction in lung tissue.

• Food Science and Preservation
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• v.23 no.6
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• pp.890-898
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• 2016

The purpose of this paper is to investigate potential anti-inflammatory and anti-oxidant effects of Tenebrio molitor. Macrophage cell response by outside stimulation leads expression of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), $interleukin-1{\beta}$ ($IL-1{\beta}$), and trigger expression of genes which are affected by inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), resulting in formation of inflammatory factors like nitric oxide (NO) and Prostaglandin $E_2$ (PGE2). Cell viability was determined by MTT assay. In order to investigate anti-inflammatory agents, the inhibitory effects on the production of lipopolysaccharide (LPS)-induced NO in RAW 264.7 cells were examined. T. Molitor significantly decreased the production of NO in a dose-dependent manner, and also reduced the expression of iNOS, a COX-2 protein. As a result, the levels of protein such as $PGE_2$, iNOS, COX-2 and MARKs were significantly reduced compared to non-treated group in T. Molitor water extract (TDW) treated group. Also, antioxidant effect of T. Molitor were investigated using DPPH, ABTS+ and superoxide anion radical scavenging activity tests in cell-free system. Antioxidant activity of T. molitor was found low in the DPPH radical scavenging test while high in the ABTS+ and superoxide anion radical scavenging activity tests. These results show that TDW could be an effective anti-pro-inflammatory and anti-oxidant agent.

• Food Science and Preservation
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• v.25 no.1
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• pp.107-116
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• 2018

The aim of this study is to investigate the antioxidant and intracellular anti-inflammatory efficacy of blueberry leaf extracted with hot water (BLW), 70% ethanol (BLE), and 70% acetone (BLA) in RAW 264.7 macrophages. In order to evaluate the anti-inflammatory effect of blueberry leaf extracts, RAW 264.7 macrophages were stimulated with lipopolysaccharide (LPS) to induce the production of inflammation-related factors, which were measure by Western blotting and real-time PCR methods. i-NOS, COX-2 protein, and mRNA expression showed concentration-dependent decrease. The decreases in the mRNA expression levels of interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and prostaglandin $E_2$ ($PGE_2$) were concentration-dependent. Further, the antioxidant effects of blueberry leaf on total polyphenol contents, electron donating ability and $ABTS^+$ radical scavenging activity were evaluated. The total polyphenol contents of BLW, BLE, and BLA were $217.04{\pm}2.98$, $156.72{\pm}3.90$, and $182.88{\pm}3.02mg\;TAE/g$, respectively, while the electron donating abilities at $1,000{\mu}g/mL$ of BLW, BLE, and BLA were 81.7, 79.6, and 79.3%, respectively. The $ABTS^+$ radical scavenging activity was fond to be concentration dependent. The nitric oxide (NO) production inhibition activities at $50{\mu}g/mL$ of BLW, BLE, and BLA were 35.1, 42.4 and 42.7%, respectively. In conclusion, the antioxidant and anti-inflammatory test results indicate that blueberry leaf extracts (BLW, BLE, and BLA) can be used as potential anti-inflammatory agents.