Background: Synergistic antitumor effects of the combined chemoimmunotherapy based on dendritic cells have been reported recently. The aim of this study is to search new applicability of gefitinib into the combination treatment through the confirmation of gefitinib effects on the monocyte derived dendritic cells (moDCs); most potent antigen presenting cell (APC). Methods: Immature and mature monocyte-derived dendritic cell (im, mMoDC)s were generated from peripheral blood monocyte (PBMC) in Opti-MEM culture medium supplemented with IL-4, GM-CSF and cocktail, consisting of TNF-${\alpha}$ (10 ng/mL), IL-$1{\beta}$ (10 ng/mL), IL-6 (1,000 U/mL) and $PGE_2$ ($1{\mu}/mL$). Various concentrations of gefitinib also added on day 6 to see the influence on immature and mature MoDCs. Immunophenotyping of DCs under the gefitinib was performed by using monoclonal antibodies (CD14, CD80, CD83, CD86, HLA-ABC, HLA-DR). Supernatant IL-12 production and apoptosis of DCs was evaluated. And MLR assay with $[^3H]$-thymidine uptake assay was done. Results: Expression of CD83, MHC I were decreased in mMoDCs and MHC I was decreased in imMoDCs under gefitinib. IL-12 production from mMoDCs was decreased under $10{\mu}M$ of gefitinib sinificantly. Differences of T cell proliferation capacity were not observed in each concentration of geftinib. Conclusion: In spite of decreased expressions of some dendritic cell surface molecules and IL-12 production under $10{\mu}M$ of gefitinib, significant negative influences of gefitinib in antigen presenting capacity and T cell stimulation were not observed.
Atractylodes macrocephala is a perennial herb and is a member of the Compositae family. This plant is known to contain various bioactive constituents indicating anti-inflammatory, neuroprotective, anti-oxidant, immunological enhancement, and gastroprotective effects. In this investigation, we isolated four compounds with similar chemical structures from A. macrocephala, and evaluated their anti-inflammatory effects. Among the four compounds, compound 2(atractylenolide II) showed the second-best inhibitory effect on the lipopolysaccharide(LPS)-induced production of nitric oxide in RAW264.7 macrophages and BV2 microglial cells. Compound 2 also inhibited the LPS-induced the production of prostaglandin E2(PGE2), and the expression of inducible nitric oxide synthase(iNOS) and cyclooxygenase(COX)-2 proteins in both cells. In addition, compound 2 suppressed the production of pro-inflammatory cytokines including interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. These inhibitory effects were contributed by inactivation of nuclear factor kappa B(NF-κB) and mitogen-activated protein kinases(MAPKs) pathways by treatment with compound 2. This compound did not induce the expression of heme oxygenase(HO)-1 protein indicating that the anti-inflammatory effect of compound 2 was independent with HO-1 protein. Taken together, these results suggested that atractylenolide II can be a candidate material to treat inflammatory diseases.
We examined the anti-inflammatory properties of Nostoc commune HCW0811 in lipopolysaccharide-stimulated RAW264.7 macrophage cells. The anti-inflammatory activity of HCW0811 on viability of treated cells was assessed by measuring the level of expression of NO, prostaglandin E2 and pro-inflammatory cytokines, namely interleukin-1β, interleukin-6, and tumor necrosis factor-α in HCW0811 treated RAW 264.7 macrophages. HCW0811 was non-toxic to cells and inhibited the production of cytokines in a concentration-dependent manner. In addition its treatment suppressed the production of pro-inflammatory cytokines in a dose-dependent manner, and concomitantly decreased the protein expressions of inducible NO synthase and cyclooxygenase-2. Moreover, the levels of the phosphorylation of mitogen-activated protein kinase family proteins such as extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B were reduced by HCW0811. These findings suggest that the HCW0811 collected from Daejeon National Cemetery have anti-inflammatory effects, and demonstrated its efficacy in cell-based in vitro assays.
Resveratrol, a phytoalexin found at high levels in grapes and in grape products such as red wine, has been reported to possess a wide range of biological and pharmacological activities including antioxident, anti-inflammatory, anti-mutagenic, and anti-carcinogenic effects. According to recent studies, this compound is an effective inhibitor of cell growth in general, triggers partial arrest of the cell cycle and induce apoptosis. In this study, the anti-proliferative effects of resveratrol in A549 human lung carcinoma cells were investigated. It is shown that resveratrol induced the growth inhibition in a time-dependent manner and morphological changes of A549 cells, which were associated with induction of S phase arrest of the cell cycle and apoptotic cell death. The Bcl-$X_L$levels were markedly down-regulated in resveratrol treated cells, however, Bax and Bcl-2 were remained unchanged. Resveratrol treatment induced the proteolytic degradation of Sp-l and proliferating cell nuclear antigen protein, and inhibited the expression of $\beta$-catenin protein. Resveratrol treatment also induced a marked up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 and inhibited the kinase activities of Cdk2 and Cdk4. In addition, resveratrol treatment inhibited the levels of cyclooxygenase (COX)-2 mRNA and protein, and the release of prostagladin E2 without alteration of COX-1 expression. Taken together, these findings suggest that resveratrol may be a potential chemotherapeutic agent for the control of human lung carcinorma cells.
Jeon, In Hwa;Kang, Hyun Ju;Lee, Hyun-Seo;Shin, Jun Ho;Park, Yong Gyoun;Jeong, Seung-Il;Jang, Seon Il
Korean Journal of Food Science and Technology
/
v.46
no.4
/
pp.505-510
/
2014
Kojongsi persimmon (Diospyros kaki L.) is the major cultivar of dried persimmon in Korea. The purpose of this study was to investigate the antioxidant and anti-inflammatory activities of water-soluble extracts from the calyx (PCE), peel (PPE) and leaf (PLE) of Kojongsi persimmon. PCE showed the highest total phenolic and flavonoid contents. In addition, the antioxidant activities (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), nitric oxide and reducing power) of PCE were higher than those of PPE and PLE. Moreover, PCE, PPE and PLE significantly suppressed the production of inflammatory mediators (nitric oxide and $prostaglandinE_2$) and pro-inflammatory cytokines (tumor necrosis factor-${\alpha}$ and interluekin-$1{\beta}$) by lipopolysaccharide-stimulated RAW 264.7 cells in a dose-dependent manner. PCE showed the highest anti-inflammatory activity. Thus, these results suggest that the calyx of Kojongsi persimmon may be highly valuable as a natural product owing to its high-quality functional components as well as its-antioxidant, ant-iinflammatory activities.
Kim, Huiju;Jung, Taek Kyu;Kim, Ja Young;Yoon, Kyung-Sup
Journal of the Korean Applied Science and Technology
/
v.36
no.2
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pp.434-447
/
2019
Polyethylene glycol (PEG) is widely used in cosmetics as a surfactant, detergent and emulsifier. During the manufacturing process, 1,4-dioxane, which is toxic to humans, can be produced as a by-product by dimerization of ethylene oxide. As consumers' interest in cosmetic ingredients has increased, the need for safe emulsion research without PEG ingredients in the personal care market has increased. With increasing consumer interest in cosmetic ingredients, the need for safer emulsion research without the PEG ingredient in the personal care market has increased. In this study, we aimed to develop and stabilize nanoemulsion formulation without PEG. Response Surface Methodology (RSM) was used to develop optimized nanoemulsion formulations. Surfactant content (2~4%), oil content (4~8%) and polyol content (12~24%) were set as independent variables as a result of preliminary experiments for determining independent variables and ranges. The particle size, zeta potential, turbidity, and polydispersity index of the formulation were measured as response variables. As a result of measurement of the prepared nanoemulsion by FIB (Focused ion beam), spherical particles were found to have a size distribution of 100 to 200 nm. The stability of each formulation was evaluated for 30 days at each temperature ($4^{\circ}C$, $25^{\circ}C$, and $45^{\circ}C$). The optimal formulation considering the optimum particle size, turbidity, polydispersity index and zeta potential was found to be surfactant (2%), oil (8%) and polyol (24%).
Jeon, Chang Kwon;Park, Sang Mi;Park, Chung A;Byun, Sung Hui;Kim, Sang Chan
Herbal Formula Science
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v.27
no.2
/
pp.101-120
/
2019
PURPOSE : Euonymi Lignum Suberalatum (EL) is the stem fin of Euonymi alatus. In traditional Korean medicine, EL is used for treatment of uterine bleeding, metritis and static blood. Recently, many studies have reported several pharmacological effects of EL including anticancer, antimicrobial, antidiabetic activity, and anti-oxidative stress. However, the mechanisms underlying anti-inflammatory effects by the EL is not established. METHODS : To investigate anti-inflammatory effects of Euonymi Lignum Suberalatum Water (ELWE), Raw 264.7 cells were pre-treated with $10-300{\mu}g/mL$ of ELWE, and then exposed to $1{\mu}g/mL$ of LPS. Levels of NO, IL-6, $IL-1{\beta}$ and $TNF-{\alpha}$ were detected by ELISA kit. Expression of pro-inflammatory proteins were determined by immunoblot analysis. To evaluate the anti-inflammatory effect in vivo, rat paw edema volume, and expressions of COX-2 and iNOS proteins in carrageenan (CA)-induced rat paw edema model. RESULTS : NO production activated by LPS, was decreased by $30-300{\mu}g/mL$ of ELWE. Production of inflammatory mediators such as $TNF-{\alpha}$, ILs, $PGE_2$ were decreased by ELWE 100 and $300{\mu}g/mL$. In addition, ELWE reduced LPS-mediated iNOS and COX-2 expression. Moreover, ELWE increased $I-{\kappa}B{\alpha}$ expression in cytoplasm and decreased $NF-{\kappa}B$ expression in nucleus. In vivo study, ELWE reduced the increases of paw swelling, and expression of iNOS and COX-2 proteins in paw edema induced by CA injection. CONCLUSION : The results indicate that ELWE could inhibit the acute inflammatory response, via modulation of $NF-{\kappa}B$ activation. Furthermore, inhibition of rat paw edema induced by CA is considered as clear evidence that ELWE may be a useful source to treat acute inflammation.
Portulaca oleracea L. (PL) has been used in traditional medicine herb for treatment of various diseases, such as diarrhea, dysentery, and skin inflammation. Previous studies have shown that the PL regulates the inflammation by inhibition of pro-inflammatory cytokines. Although PL might have improvement effects of intestinal function and bioactive effects, there are not enough studies to demonstrate. This study investigated the effects of KDC16-2 on the improvement of intestinal function and anti-inflammatory effects in vivo and in vitro. The improvement effect of intestinal function was measured fecal amount, water content and intestinal transit rate in KDC16-2 treated ICR mice. As results, compared with the control group, the KDC16-2 group showed a significant increase in wet fecal weight, dry fecal weight and fecal water content. The intestinal transit rate of KDC16-2 group was significantly increased. Based on the results, KDC16-2 is considered to have effects on improving intestinal function. The effect of anti-inflammatory demonstrated by using dextran sulfate sodium (DSS)-induced colitis mice. The mice were administered 3% DSS along with KDC16-2 (100, 300 mg/kg) for 14 days. DSS-induced colitis mice were significantly ameliorated in KDC16-2 treated group, including body weight loss, colon length shortening, tight junction protein of colon and histological colon injury. The levels of inflammatory mediators (IgG2a, IgA, C-reactive protein and Myeloperoxidase) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-${\alpha}$, Interleukin (IL)-6) which are involved in inflammatory responses were increased in the DSS-treated group as compared to those in the control group, and the levels were significantly decreased in the KDC16-2 groups. In addition, we investigated the impact of KDC16-2 on lipopolysaccharide (LPS)-induced inflammatory responses in J774A.1 cells. KDC16-2 inhibited production of prostaglandin E2 (PGE2) and reactive oxygen species (ROS). These results suggested that the KDC16-2 could effectively alleviate the dysfunction of intestinal and inflammatory mediators. Thus, these KDC16-2 can be potentially used as health functional food of intestinal.
Jae In, Jung;Hyun Sook, Lee;So Mi, Kim;Soyeon, Kim;Jihoon, Lim;Moonjea, Woo;Eun Ji, Kim
Nutrition Research and Practice
/
v.16
no.6
/
pp.685-699
/
2022
BACKGROUND/OBJECTIVES: Platycodon grandiflorum (PG) has long been known as a medicinal herb effective in various diseases, including bronchitis and asthma, but is still more widely used for food. Fermentation methods are being applied to increase the pharmacological composition of PG extracts and commercialize them with high added value. This study examines the hydrolyzed and fermented PG extract (HFPGE) fermented with Lactobacillus casei in RAW 264.7 cells, and investigates the effect of amplifying the immune and the probable molecular mechanism. MATERIALS/METHODS: HFPGE's total phenolic, flavonoid, saponin, and platycodin D contents were analyzed by colorimetric analysis or high-performance liquid chromatography. Cell viability was measured by the MTT assay. Phagocytic activity was analyzed by a phagocytosis assay kit, nitric oxide (NO) production by a Griess reagent system, and cytokines by enzyme-linked immunosorbent assay kits. The mRNA expressions of inducible nitric oxide synthase (iNOS) and cytokines were analyzed by reverse transcription-polymerase chain reaction, whereas MAPK and nuclear factor (NF)-κB activation were analyzed by Western blots. RESULTS: Compared to PGE, HFPGE was determined to contain 13.76 times and 6.69 times higher contents of crude saponin and platycodin D, respectively. HFPGE promoted cell proliferation and phagocytosis in RAW 264.7 cells and regulated the NO production and iNOS expression. Treatment with HFPGE also resulted in increased production of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, C-X-C motif chemokine ligand10, granulocyte-colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-1, and the mRNA expressions of these cytokines. HFPGE also resulted in significantly increasing the phosphorylation of NF-κB p65, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. CONCLUSIONS: Taken together, our results imply that fermentation and hydrolysis result in the extraction of more active ingredients of PG. Furthermore, we determined that HFPGE exerts immunostimulatory activity via the MAPK and NF-κB signaling pathways.
Lee, Sun Young;Kim, Yoo-Sun;Lim, Ji Ye;Chang, Namsoo;Kang, Myung-Hee;Oh, Se-Young;Lee, He-Jin;Kim, Hyesook;Kim, Yuri
Nutrition Research and Practice
/
v.8
no.3
/
pp.249-256
/
2014
BACKGROUND/OBJECTIVES: The traditional Korean diet is plant-based and rich in antioxidants. Previous studies have investigated the potential health benefits of individual nutrients of Korean foods. However, the cumulative effects of a Korean diet on inflammation remain poorly understood. Therefore, the aim of this study was to investigate the anti-inflammatory effects of a plant-based Korean diet. MATERIALS/METHODS: Using data from the Fifth Korean National Health and Nutrition Examination Survey, 75 individual plant food items were selected which represent over 1% of the total diet intake of the Korean diet. These items were classified into ten different food groups, and the vegetable (Veg) and fruit (Fruit) groups were studied based on their high antioxidant capacity. For comparison, a mixture of all ten groups (Mix) was prepared. To produce a model of inflammation with which to test these Veg, Fruit, and Mix plant-based Korean food extracts (PKE), RAW264.7 macrophages were treated with lipopolysaccharide (LPS). RESULTS: Levels of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$), as well as protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were found to be lower following PKE treatment. Furthermore, PKE treatment was found to suppress tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) via the nuclear transcription factor kappa-B ($NF-{\kappa}B$) signaling pathway. Overall, the Mix group exhibited the greatest anti-inflammatory effects compared with Veg and Fruit PKE group. CONCLUSIONS: Inhibition of LPS-induced pro-inflammatory mediators by the PKE tested was found to involve an inhibition of NF-kB activation. Moreover, PKE tested have the potential to ameliorate various inflammation-related diseases by limiting the excessive production of pro-inflammatory mediators.
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