• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.4
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• pp.377-382
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• 2007

This study was designed to investigate the effect of Plebeiae Herba (Salvia plebeia R. Br.) on the proliferation of AGS cell lines and the activation of splenocytes. In an anti-cancer test using AGS cells, water and ethanol extracts of Plebeiae Herba inhibited the growth of AGS cell lines and morphological changes were also observed in a dose-dependent manner. Water extract of Plebeiae Herba showed growth-inhibitory effect of 43.3% at $1,000{\mu}g/mL$ and 69.7% at $3,000{\mu}g/mL$. Ethanol extracts of Plebeiae Herba showed growth-inhibitory effect of approximately 37.3% for $1,000{\mu}g/mL$ and 75.8% for $3,000{\mu}g/mL$. The Plebeiae Herba induced the proliferation of spleen cells and increased interleukin (IL)-2, interleukin (IL)-6 and tumor necrosis factor $(TNF)-{\alpha}$. In conclusion, these results suggest that the Plebeiae Herba seems to have antiproliferationg effect against the AGS cell and acts as a potent immunomodulator.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.7
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• pp.929-937
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• 2016

The purpose of this study was to investigate the effect of Acanthopanax senticosus extract (ASE) (ethanol : DW=1:1, v/v) on inhibition of type 2 diabetes using an OLETF rat model via regulation of HbA1c and AGEs levels. Supplementation with ASE 0.1% and 0.5% effectively lowered levels of glucose, insulin, oral glucose tolerance test, and Homa-insulin resistance, suggesting reduced insulin resistance. Blood levels of HbA1c and AGEs were significantly reduced in a dose-dependent manner. As oxidative stress plays a key role in accelerating production of HbA1c and AGEs, which worsen symptoms of type 2 diabetes, levels of malonaldehyde and pro-inflammatory cytokines were measured. Lipid peroxidation in both blood and liver tissues was significantly reduced, and induction of pro-inflammatory cytokines interleukin-${\beta}$ and tumor necrosis factor-${\alpha}$, which elevate production of HbA1c and AGEs, was inhibited (P<0.05). To evaluate the possible cellular events after AGEs receptor activation, genetic expression of protein kinase C (PKC)-${\delta}$ and transforming growth factor (TGF)-${\beta}$ was measured by real-time polymerase chain reaction. Supplementation with both ASE 0.1% and 0.5% significantly inhibited mRNA expression of PKC-${\delta}$ and TGF-${\beta}$, indicating that ASE may have beneficial effects on preventing insulin-resistant cells or tissues from progressing to diabetic complications. Taken together, ASE has potential to improve type 2 diabetes by inhibiting insulin resistance and protein glycosylation, including production of HbA1c and AGEs. Anti-oxidative activities of ASE are a main requisite for reducing production of HbA1c and AGEs and are also related to regulation of the PKC signaling pathway, resulting in suppression of TGF-${\beta}$, which increases synthesis of collagen, prostaglandin, and disease-related proteins.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.12
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• pp.1663-1670
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• 2012

The inhibitory effects of rose hip (Rosa canina L.) water extracts from two different manufactures on osteoarthritis was comparatively investigated in primary cultures of rat cartilage cells. To identify the effects of rose hip extracts against $H_2O_2$ (300 ${\mu}M$, 2 hr) treatment, cell survival was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell survival increased by rose hip extracts in the range of 100 to 600 ${\mu}g/mL$ of $H_2O_2$ treatment. To determine the anti-inflammatory effects of rose hip extracts, tumor necrosis factor alpha (TNF-${\alpha}$), nitric oxide (NO), and Cox-2 expression were measured after lipopolysaccharide (LPS) activation. TNF-${\alpha}$ level with rose hip extract treatment was decreased by 27.4% and 31.9% at 600 ${\mu}g/mL$ of $H_2O_2$ treatment. Nitric oxide was inhibited by rose hip extract at 100~600 ${\mu}g/mL$ of $H_2O_2$ treatment in a dose-dependent manner. In addition, Cox-2 protein expression was dose-dependently decreased while Cox-1 had no change in expression level. The severity of osteoarthritis is controlled by a balance between anabolic and catobolic factors in an articulation, therefore the expression of these factors plays a critical role in preventing osteoarthritis. In measuring anabolic factors, the genetic expression of collagen type I increased with rose hip treatment, while the genetic expression of collagen II did not change. In addition, the genetic expression of aggrecan (proteoglycan core protein) was significantly increased. while the genetic expression of matrix metalloproteinase (MMP) 3, 7 and 13, known catabolic factors, was significantly inhibited by treatment with rose hip extract. The expression of MMP13 was especially highly influenced. In conclusion, rose hip water extracts show inhibitory effects on cell death by $H_2O_2$ mediated oxidative stress, which is related to inhibitory effects on inflammation due to TNF-${\alpha}$, NO, and Cox-2. The ability of rose hip extracts to ameliorate inflammation in primary cultures of cartilage cells seems to associate with an increased genetic expression of specific anabolic factors, collagen type I and aggrecan, and a decreased expression of catabolic factors, MMPs (3, 7, and 13). However, there were no significant differences between rose hip extracts from the two manufacturers.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.1
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• pp.25-31
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• 2009

This study was carried out to investigate the mutagenic, antimutagenic, cytotoxicity and antitumor effects of Adenophora triphylla (AT). AT was extracted with 70% ethanol and then further fractionated to hexane, chloroform, ethyl acetate, butanol and water. Antimutagenic, cytotoxicity and antitumor effects of AT extracts were measured by using Ames test, SRB method, and the tumor growth inhibition test. AT extracts did not show any mutagenicity in the Ames test; however, 70% ethanol extracts and its fractions had strong antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). The ethyl acetate fraction of AT (200 ${\mu}g$/plate) showed approximately 66.5% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain, whereas 83.3% and 75.1% inhibitions were observed on the mutagenesis induced by MNNG and 4NQO against TA100 strain. In anticancer effects, the cytotoxicity of AT extract and its fractions against cancer cell lines including human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human breast adenocarcinoma (MCF-7), human gastric carcinoma (AGS), human lung carcinoma (A549) and transformed primary human embryo kidney (293) were investigated. The treatment of 1 mg/mL AT ethyl acetate faction had the highest cytotoxicity of 79.9%, 74.9%, 66.0%, 71.0% and 74.3% against HeLa, Hep3B, MCF-7, AGS and A549 cells, respectively. In contrast, the extract and its fractions showed only $3{\sim}36%$ cytotoxicity for a normal human kidney cell line (293). In vivo anti-cancer effect of Adenophora triphylla extract was tested using Balb/c mice transplanted sarcoma-180 cells. Adenophora triphylla ethyl acetate fraction showed the highest inhibition rate of 37.2% at the 50 mg/kg concentration.

• Journal of Gastric Cancer
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• v.2 no.2
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• pp.73-80
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• 2002

In spite the fact that H. pylori infection might be the causative organisms of acute and chronic gastritis, peptic ulcer diseases and the definition as the class I carcinogen by WHO IARC, still debates exist about the relationship between H. pylori and gastric carcinogenesis. Epidemiological and animal studies demonstrated a link between gastric cancer and chronic infection with H, pylori, but the exact mechanism responsible for the development of gastric cancer in H. pylori-infected patients still remain obscure. In order to declare the clear association, definate evidences like that decrement in the incidence of gastric cancer after the eradication of H. pylori in designated area compared to noneradicated region or the blockade of specific mechanism acting on the carcinogenesis by H. pylori infection. The other way is to identify the upregulating oncogenes or downregulating tumor suppressor genes specifically invovled in H. pylori-associated carcinogenesis. For that, we established the animal models using C57BL/6 mice strain. Already gastric carcinogenesis was developed in Mongolian gerbils infected with H. pylori, but there has been no development of gastric cancer in mice model infected with H. pylori after long-term evaluation. Significant changes such as atrophic gastritis were observed in mice model. However, we could observe the development of mucosal carcinoma in the stomach of transgenic mice featuring the loss of TGF-beta sig naling by the expressions of dominant negative forms of type II receptor specifically in the stomach. Moreover, the incidence of gastric adenocarcinoma was significantly increased in group administered with both MNU and H. pylori infection than MNU alone, signifying that H. pylori promoted the gastric carcinogenesis and there might be host susceptibility genes in H. pylori-associated gastric carcinogenesis. Based on the assumption that chronic, uncontrolled inflammation might predispose to carcinogenesis, there have been several evidences showing chronic atrophic gastritis predisposed to gastric carcinogenesis in H. pylori infection. Although definite outcome of chemoprevention was not drawn after the longterm administration of anti-inflammatory drug in H. pylori infection, the actual incidence of atrophic gastritis and molecular evidence of chemoprevention could be obtained. Selective COX-2 inhibitor was effective in decreasing the development of gastric carcinogenesis provoked by H. pylori infection and carcinogen like in chemoprevention of colon carcinogenesis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.8
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• pp.1183-1189
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• 2013

We investigated the effects of oyster shell extract (OSE) on papain-induced osteoarthritis in C57BL/6J mice. Osteoarthritis was induced in mice by a papain injection into the knee joint. The mice were divided into a total of five groups (n=8). The normal group was untreated, whereas the papain group (negative control) was induced with osteoarthritis and treated with water daily. The papain+DS group (positive control) was treated with diclofenac sodium. Papain+OSE groups were treated with OSE concentrations of 100 and 200 mg/kg/bw for 20 days. Proteoglycan content in articular cartilage was analyzed through safranine-O fast green staining and H&E staining. The histopathological changes in cartilage were measured by the Rudolphi score approach. The contents of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, and IL-6 in plasma were analyzed by the ELISA method. After experiments, body weights of the treated groups were not significantly different compared with the normal group. Cartilage loss and joint instability significantly improved in a dose-dependent manner in the OSE-treated group compared with the papain group (P<0.05). Proteoglycan content was significantly higher in the OSE-treated group than the papain group (P<0.05). Osteoarthritis scores of the OSE-treated group were significantly decreased compared with the papain group (P<0.05). TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 content in the plasma of the papain+OSE treated groups significantly decreased in a dose-dependent manner compared with the papain group (P<0.05). These results suggest that OSE treatment might have anti-arthritic effects on papain-induced osteoarthritis in C57BL/6J mice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.5
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• pp.664-672
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• 2015

In order to develop new immuno-stimulating ingredients from mature leaves of green tea, crude polysaccharides were isolated from pectinase digests of tea leaves (green tea enzyme digestion, GTE-0), after which their immuno-stimulating activities and chemical properties were examined. GTE-0 mainly contained neutral sugars (54.9%) such as glucose (14.2%), arabinose (12.2%), rhamnose (11.1%), and galacturonic acid (45.1%), which are characteristic of pectic polysaccharides. The anti-complementary activity of GTE-0 was similar to that of polysaccharide K (used as positive control). Number of morphologically activated macrophages was significantly increased in the GTE-0-treated group. GTE-0 significantly augmented $H_2O_2$ and reactive oxygen species production by murine peritoneal macrophage cells in a dose-dependent manner, whereas production of nitric oxide showed the highest activity at a dose of $100{\mu}g/mL$ among all tested concentrations. Murine peritoneal macrophages stimulated with GTE-0 showed enhanced production of various cytokines such as interleukin (IL)-6, IL-12, and tumor necrosis factors-${\alpha}$ in a dose-dependent manner. Further, GTE-0 induced higher phagocytic activity in a dose-dependent manner. In ex vivo assay for cytolytic activity of murine peritoneal macrophages, GTE-0-treated group showed significantly higher activity compared to the untreated group at an effector-to-target cell ratio of 20. The above results lead us to conclude that polysaccharides from leaves of green tea have a potent immuno-stimulating effect on murine peritoneal macrophage cells.

• Pediatric Infection and Vaccine
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• v.12 no.1
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• pp.75-85
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• 2005

Purpose : Fungal infection is one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B(ABV) and itraconazole(ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-$1{\beta}$(IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines(IL-4, IL-1Ra) by ABV and ITZA. Methods : From March 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-$1{\beta}$, TNF-${\alpha}$, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results : Empirical antifungal agents were given to 37 patients(ABV 20, ITZA 17), and 30 patients(ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-$1{\beta}$ was increased in ABV treatment group and the ratio of IL-1Ra/IL-$1{\beta}$ is markedly decreased in ABV treatment group while increased in ITZA group. Conclusion : ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.672-683
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• 2004

Background: The treatment results of the advanced lung carcinoma is not satisfactory with the present therapeutic modalities: surgical resection, anti-cancer chemotherapy, and radiotherapy or combination therapy. To predict the prognosis of the non-small-cell lung carcinoma, TNM classification has been was as the basic categorization; however, it has been not satisfactory. It is necessary to consider the causes and the prognosis of the lung carcinoma from another points of view rather the conventional methods. We intended to find out the relationship between the major apoptotic factor, p53 gene and the prognosis of the patient with lung carcinoma. Material and Method: Three hundreds and fifty-nine patients with lung carcinoma who underwent surgery were analysed. We observed p53 protein accumulated in the cellular nuclei. The p53 protein was detected by immuno-histo-chemical method. We collected information of the patient retrospectively. Result: p53 protein densities were observed in 40% in average as a whole. The protein density was 44 percent in man, 25 percent in woman, 49 percent in the squamous cell carcinoma, and 38 percent in the adenocarcinoma. There were significant correlations between the p53 protein density and the mortality in the squamous cell carcinoma (p=0.025), follow-up duration in TNM stage I group (p=0.010), and follow-up duration in the lobectomy patient group (p=0.043), and tumor cell differentiation (p=0.009). p53 protein densities were significantly different between the lobectomy and the pneumonectomy group (p=0.044). Conclusion: The authors found that p53 protein had some correlations with the prognosis of the lung cancer partially in some factors. We suggest the p53 protein density could be used as a marker of prognosis in the non-small-cell lung carcinoma.

• Journal of Life Science
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• v.30 no.2
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• pp.113-121
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• 2020

Macrophages are initiators for regulating a host's defenses to eliminate pathogens and trigger tissue repair. Macrophages are classified into two types: classically (M1) activated macrophages and alternatively (M2) activated macrophages. M1-phenotype macrophages directly or indirectly kill infectious organisms and tumor cells via pro-inflammatory responses, whereas M2-phenotype macrophages remodel wounded tissue through anti-inflammatory responses. In this paper, we investigated how Phellinus linteus hot water extract passed from Diaion HP-20 resin (PLEP) regulates polarization of M1-like or M2-like macrophages in human THP-1 cells. PLEP did not have cytotoxicity at a high concentration of 300 ㎍/ml. We observed morphological alteration of the THP-1 cells, which are stimulated by PLEP, LPS/INF-γ (M1 stimulators) or IL-4/IL13 (M2 stimulators). PLEP exposure induced morphology contiguous with LPS/INF-γ. qPCR was also performed to determine whether PLEP influences M1 or M2 polarization-related genes. M1-phenotype macrophage-specific genes, such as TNF-α, IL-1β, IL-6, IL-8, CXCL10 and CCR7, were enhanced by PLEP in a dose-dependent manner similar to LPS/INF-γ. Conversely, M2-phenotype-specific genes, such as MRC-1, DC-SIGN, CCL17 and CCL22, were suppressed by PLEP. PLEP also significantly up-regulated secretory inflammation cytokines related to M1 polarization of macrophages, including TNFα, IL-1β and IL-6, which was similar to the gene expression. Further, MAPK and NF-κB signaling were increased by treatment with PLEP, resulting in enhancement of cytokine secretion. PLEP might therefore be used as a promising booster of pro-inflammatory responses through M1 polarization of human THP-1 cells.