• The Journal of Korean Medicine
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• v.34 no.3
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• pp.69-85
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• 2013

Objectives: This study investigated the anti-osteoarthritic effects of Kyejiinsam-tang (hereinafter referred to KIT) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods: Anti-oxidative effects of KIT were measured by scavenging activities of DPPH, reactive oxygen species (ROS) and nitric oxide (NO). Scavenging activities of anti-oxidation in lipopolysaccharide (LPS)-treated RAW 264.7 cells were also measured for inhibitory effects against the production of inflammatory mediators (tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, interleukin-6). Osteoarthritis was induced in rats by injecting MIA in the knee joint. Rats were divided into a total of 4 groups (n=6). The normal group were not treated at all without inducing osteoarthritis whereas the control group were induced for osteoarthritis by MIA and oral medicated physiological saline per day. The positive comparison group was injected with MIA and after 7 days, 2 mg/kg of Indomethacin. The experimental group was injected with MIA and after 7 days was medicated with 34 mg/kg of KIT. Indomethacin and KIT were orally-medicated for each substance a total of 4 weeks, once per day. Weight-bearing on hind legs was measured every week after MIA injection. At the end of the experiment (5 weeks after MIA injection), micro CT (computed tomography)-arthrography and histopathological examinations on the articular structures of knee joint were performed. The effect on inflammatory cytokines and immunological cells in synovial fluid was measured. Volume of cartilage was measured by micro CT-arthrography. Injury to synovial tissue was measured by H & E (hematoxylin and eosin), Safranin-O immunofluorescence. Results: 1. Cytotoxicity against hFCs was insignificant. 2. KIT showed the potent full term for DPPH. 1. NO was significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and ROS was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 2. IL-6 and IL-$1{\beta}$ were significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and TNF-${\alpha}$ was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 1. In hind legs weight-bearing measurement, level of weight increased. 2. Functions of liver and kidney were not affected. 3. IL-$1{\beta}$ was significantly reduced and TNF-${\alpha}$, IL-6 were also reduced but not significantly. 4. PGE2 (prostaglandin E2), LTB4 (leukotriene B4) were significantly reduced in the KIT group. 5. MMP-9 (matrix metalloproteinase-9), TIMP-1 (tissue inhibitor of metalloproteinases-1) and Osteocalcin were significantly reduced in the KIT group. 6. Destruction of cartilage on micro CT arthrography was reduced but had no significant differences. 7. Histopathologically, injury to synovial membrane of the KIT group was decreased and proteoglycan content of KIT group was increased. Conclusions: According to this study, Kyejiinsam-tang has inhibiting effect on the progression of arthritis in MIA-induced osteoarthritis rat. Kyejiinsam-tang has anti-oxidants and anti-inflammation effects, and is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

• Journal of Life Science
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• v.26 no.4
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• pp.439-445
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• 2016

Soybean leaves, a Korean edible plant material, have been reported to prevent the development of osteoporosis and breast cancer. Based on this rational, soybean fallen leaves ethanolic extract (SBFL) was used for the experiment of cell invasion related to metastasis and antioxidant activity. The effect of SBFL on matrix metalloproteinases (MMPs) in human fibrosarcoma cells, HT1080 as well as its anti-oxidant activity was investigated in this study. The effect of SBFL on scavenging activity of reactive oxygen species was evaluated in vitro using lipid peroxidation assay,DPPH radical and reducing power assay. SBFL showed the positive effects on antioxidant activity, compared with vitamin C and vitamin E used as positive controls. Furthermore, SBFL showed cytotoxicity above 16 µg/ml in MTT assay. In particular, it was found that SBFL decreased the activation of MMP-9 stimulated by phorbol 12-myristate 13-acetae (PMA) and phenazine methosulfate (PMS). SBFL treatment increased the expression levels of p-FoxO-1 and SOD-1. Moreover, SBFL inhibited cell invasion stimulated by vascular endothelial growth Factor (VEGF). These results indicate that SBFL could inhibit cell invasion related to the activation of MMP-9 and oxidative stress, suggesting that it could be available as a main ingredient for prevention of metastasis.

• Korean Journal of Food Science and Technology
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• v.51 no.6
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• pp.537-542
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• 2019

Proteins were isolated from four species of edible insects, Bombyx mori, B; Tenebrio molitor, T; Protaetia brevitarsis, P; and Gryllus bimaculatus, G, and their properties were analyzed and compared with those of whey proteins. The yield of the protein isolated from raw materials was 65.0-75.0%. Among three branched chain amino acids (BCAA), the amounts of valine in all the insects were similar to that of the whey protein. The BCAA content was 16.8 and 16.4% in G and T, respectively. The total polyphenolic content and the antioxidant activity of the insect proteins were significantly higher than those of the whey proteins. Based on the sensory test of the protein powder, the whey protein could be replaced by 25% of the isolated protein from the insects, but the taste and flavor needs to be improved. Although the BCAA content of insect proteins was lower than that of the whey protein (by 73-76%), their application could be useful because of high polyphenolic content and the anti-oxidative activity.

• Environmental Mutagens and Carcinogens
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• v.22 no.3
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• pp.142-148
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• 2002

Although ionizing radiation (IR) has been used to treat the various human cancers, IR is cytotoxic not only to cancer cells but to the adjacent normal tissue. Since normal tissue complications are the limiting factor of cancer radiotherapy, one of the major concerns of IR therapy is to maximize the cancer cell killing and to minimize the toxic side effects on the adjacent normal tissue. As an attempt to develop a method to monitor the degree of radiation exposure to normal tissues during radiotherapy, we investigated the transcriptional responses of human peripheral blood lymphocytes (PBL) following IR using cDNA microarray chip containing 1,221 (1.2 K) known genes. Since conventional radiotherapy is delivered at about 24 h intervals at 180 to 300 cGy/day, we analyzed the transcriptional responses ex-vivo irradiated human PBL at 200 cGy for 24 h-period. We observed and report on 1) a group of genes transiently induced early after IR at 2 h, 2) of genes induced after IR at 6 h, 3) of genes induced after IR at 24 h and on 4) a group of genes whose expression patters were not changed after IR. Since Biological consequences of IR involve generation of various reactive oxygen species (ROS) and thus oxidative stress induced by the ROS is known to damage normal tissues during radiotherapy, we further tested the temporal expression profiles of genes involved in ROS modulation by RT-PCR. Specific changes of 6 antioxidant genes were identified in irradiated PBL among 9 genes tested. Our results suggest the potential of monitoring post-radiotherapy changes in temporal expression profiles of a specific set of genes as a measure of radiation effects on normal tissues. This type of approach should yield more useful information when validated in in vivo irradiated PBL from the cancer patients.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.10
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• pp.1391-1397
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• 2016

We investigated the hepatoprotective effects of Angelica keiskei Koidzumi extract (AK) in HepG2-overexpressing cytochrome P4502E1 (CYP2E1) and C57BL/6J mice. In HepG2 cells expressing CYP2E1, cell viability and catalase activity in the ethanol-AK co-treated group significantly increased compared to those in the ethanol-treated group. In the in vivo study with C57BL/6J mice, the AK-supplemented group with ethanol liquid diet showed significantly reduced hepatic markers, including serum aspartate aminotransferase, alanine aminotransferase, and ${\gamma}$-glutamyl transferase, compared to the ethanol group without AK supplementation. AK supplementation (20 mg/kg BW/d) also significantly attenuated reactive oxygen species generation and malondialdehyde level. Notably, a low dose of AK supplementation (20 mg/kg BW/d) suppressed expression of hepatic CYP2E1 and inhibited CYP2E1 enzyme activity. These data indicate that a low dose of AK supplementation could restrain alcohol-induced hepatic damage mediated by CYP2E1.

• Korean Journal of Food Science and Technology
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• v.41 no.6
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• pp.700-705
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• 2009

Several studies have demonstrated that chlorophyll has many beneficial properties, including anti-inflammatory, anti-tumor, and antioxidant properties. Chlorophyll has been also shown to have an excellent chemopreventive potential against skin tumor. Its preventive mechanism against skin tumor, however, has not been examined in detail. Furthermore, the effects of chlorophyll on UVB-induced cellular responses have not been investigated. Solar UV radiation, in particular its UVB component, is the primary cause of many adverse biological effects, which is responsible for the photoaging and skin cancer. We investigated the preventive effects of chlorophyll a on UVB-mediated responses in human immortalized HaCaT kerationocytes and normal human fibroblast. We found that treatment of chlorophyll a markedly inhibited UVB-induced generation of reactive oxygen species and lipid peroxidation. Chlorophyll a also prevented UVB-induced MMP-1 expression and MMP-2 activation and increased Type I pN collagen synthesis. These results suggest that chlorophyll a is a potent candidate for the prevention and treatment of UVB-induced skin cancer and photoaging.

• Journal of Marine Bioscience and Biotechnology
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• v.11 no.2
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• pp.42-51
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• 2019

We compared the antibacterial activities of spermidine and astaxanthin against two gram-positive bacteria such as Streptococcus parauberis and S. iniae to find new antibacterial candidates. We also evaluated the preventive effects of spermidine against oxidative stress-induced cytotoxicity in C2C12 myoblasts. Our results indicated that spermidine has more significant antibacterial activities than astaxanthin against both two fish pathogenic bacteria as well as gram-negative bacteria Escherichia coli used as a control group. Minimum inhibitory concentration and minimum bactericidal concentration of spermidine were 0.25 mM and 1 mM against S. parauberis, 1 mM and 3 mM against S. iniae, and 0.5 mM and 1.5 mM against E. coli, respectively. In addition, the postantibiotic effect lasted from 7 h, 5 h and 6 h for S. parauberis, S. iniae and E. coli, respectively. The results also showed that the decreased C2C12 cell viability by H₂O₂ could be attributed to the induction of DNA damage and apoptosis accompanied by the increased production of reactive oxygen species, which was remarkably protected by spermidine. Additionally, the antioxidant effect of spermidine was associated with the activation of Nrf2 signaling pathway. According to the data, spermidine may be a potential lead compound which can be further optimized to discover novel antibacterial and antioxidant agents.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.1
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• pp.8-14
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• 2017

To examine the protective effect of rosmarinic acid on the aluminum of dementia inducer, cultured C6 glioma cells were treated with various concentrations of aluminum chloride ($AlCl_3$) or rosmarinic acid. The cell viability, electron donating ability (EDA), superoxide dismutase (SOD)-like activity, and inhibitory activity of lipid peroxidation were evaluated for the antioxidant effect of rosmarinic acid. In these cultures, $AlCl_3$ sowed a cytotoxic effect by decreasing the cell viability in a dose-dependent manner; then, the $XTT_{50}$ value was measured at $142.2{\mu}M$ of $AlCl_3$ after treating the cultured C6 glioma cells with media containing $120{\sim}160{\mu}M\;AlCl_3$. Therefore, its toxicity was determined as mid-cytotoxic by Borenfreund and Puerner's toxic criteria; while, vitamin E of antioxidant markedly increased the cell viability on $AlCl_3$-induced cytotoxicity in these cultures. This study showed the antioxidant effect of rosmarinic acid via several assays, such as electron donating activity (EDA), superoxide dismutase (SOD)-like activity, and inhibitory activity of lipid peroxidation. From these findings, it is suggested that the oxidative stress is involved in $AlCl_3$-induced cytotoxicity, and rosmarinic acid was effective in the protection of $AlCl_3$-induced cytotoxicity by antioxidant activity. In conclusion, natural resources, like rosmarinic acid, may be a putative antioxidant agent for the treatment of reactive oxygen species (ROS)-mediated disease, such as dementia.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1163-1169
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• 2007

Effects of Sotosaja hwan on Blood Glucose, Hyperlipidemia, Polyol Pathway and Antioxidative Mechanism in ob/ob Mouse Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Sotosaja-hwan has been known to be effective for the antiaging and composed of four crude herbs. In male ob/ob mouse in severe obesity, hyperinsulinemia and hyperlipidemia, which are features of NIDDM, the hyperglycemic activites and mechanisms of Sotosaja-hwan were examined. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. The effects of Sotosaja-hwan extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of superoxide anion radical $({\cdot}O_2)$, MDA+HAE, GSH/GSSG ratio, and also the enzyme activities involved in polyol pathway. Sotosaja-hwan lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Sotosaja-hwan treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the generation of ${\cdot}O_2$ in the kidney. Finally, MDA+HAE levels was increased and GSH/GSSG ratio was decreased in the ob/ob mice, whereas those were improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan showed the antidiabetic and anti hyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging reactive oxygen species and reducing the MDA+HAE levels in the ob/ob mice.

• Biomolecules & Therapeutics
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• v.28 no.3
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• pp.259-266
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• 2020

The present research work primarily investigated whether spinosin has the potential of improving the pathogenesis of Alzheimer's disease (AD) driven by β-amyloid (Aβ) overproduction through impacting the procession of amyloid precursor protein (APP). Wild type mouse Neuro-2a cells (N2a/WT) and N2a stably expressing human APP695 (N2a/APP695) cells were treated with spinosin for 24 h. The levels of APP protein and secreted enzymes closely related to APP procession were examined by western blot analysis. Oxidative stress related proteins, such as nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were detected by immunofluorescence assay and western blot analysis, respectively. The intracellular reactive oxygen species (ROS) level was analyzed by flow cytometry, the levels of Aβ_1-42 were determined by ELISA kit, and Thioflavin T (ThT) assay was used to detect the effect of spinosin on Aβ_1-42 aggregation. The results showed that ROS induced the expression of ADAM10 and reduced the expression of BACE1, while spinosin inhibited ROS production by activating Nrf2 and up-regulating the expression of HO-1. Additionally, spinosin reduced Aβ_1-42 production by impacting the procession of APP. In addition, spinosin inhibited the aggregation of Aβ_1-42. In conclusion, spinosin reduced Aβ_1-42 production by activating the Nrf2/HO-1 pathway in N2a/WT and N2a/APP695 cells. Therefore, spinosin is expected to be a promising treatment of AD.