Purpose: To provide the information of efficacy for herbal formulas of high frequency, it was evaluated the anti-inflammatory effect. In many studies, plantderived anti-inflammatory efficacies have been investigated for their potential inhibitory effects on lipopolysaccharide (LPS)-stimulated macrophages. This study was performed to examine the anti-inflammatory effects of herbal formulas of high frequency on LPS-stimulated RAW 264.7 cells. Methods: Anti-inflammatory activity was investigated in 25 herbal formula extracts in vitro and in vivo. To investigate the anti-inflammatory effect in vitro model, using LPS-stimulated macrophages, RAW 264.7 cell line. The productions of nitric oxide(NO), prostaglandin(PG)$E_2$, interleukin(IL)-6 and tumor necrosis factor(TNF)-$\alpha$ were examined in RAW 264.7 cells, in the presence of the herbal formulas. RAW 264.7 cells were incubated with LPS $1\;{\mu}g/mL$ and herbal formulas for 18 hours. As an in vivo, using a rat model of carrageenin-induced paw edema. The paw volume was measured at 2 and 4 hours following carrageenin-induced paw edema in rats. Results: 8 kinds of herbal formula inhibited NO production by LPS-stimulated in some concentration, but the effect of NO inhibition is weak. 12 kinds of herbal formula inhibited $PGE_2$ production by LPS-stimulated over the 30%. Among them Gumiganghwal-tang, Sagunja-tang, Samchulkunbi-tang, Insampaedok-san and Hwangryunhaedok-tang inhibited IL-6 production by LPS-stimulated but TNF-$\alpha$ was not inhibited. 12 kinds of herbal formula reduced the carrageenin-induced paw edema in rats. Particularly, 3 kinds of herbal formula(Gumiganghwal-tang, Ssanghwa-tang and Soshiho-tang) were better than indomethacin. Conclusion: These results suggest that Gumiganghwal-tang, Sangunja-tang, Samchulkunbi-tang, Insampaedok-san and Hwangryunhaedok-tang have antiinflammatory activity.
Effects of resveratrol glucosylation on the immunomodulation properties of resveratrol and on the viability of macrophage cells have been studied by using murine macrophage RAW 264.7 cells. Nitric oxide (NO) and interleukin 6 (IL-6) expression in macrophages in vitro were studied after treatment with different concentrations of (E)-resveratrol, (E)-resveratrol 3-O-${\beta}$-${\small{D}}$-glucoside (R-3-G), or (E)-resveratrol 4'-O-${\beta}$-${\small{D}}$-glucoside (R-4'-G). In vitro viability of RAW 264.7 cells after treatment with the aforementioned three compounds was also studied. As demonstrated by macrophage cell viability assays, two different resveratrol monoglucosides, R-3-G and R-4'-G, exhibited 50-80% reduced cytotoxicity in comparison to (E)-resveratrol in A549 and HepG2 cells. Compared to the resveratrol aglycon, both glucosylated resveratrol derivatives positively modulated NO and IL-6 production in macrophages positively via transcriptionally up-regulating IL-6 and iNOS expression. Conjugation of a glucose moiety on resveratrol was found to enhance the immunomodulating activity of resveratrol and the viability of RAW 264.7 cells.
Purpose : The purpose of this research was to investigate the effects of Saurui Herba Seu Rhizoma(SHSR) on Anti-inflammatory properties in Raw264.7 cell line and murine models of inflammation. Methods : To investigate the effects of Saurui Herba Seu Rhizoma(SHSR) on anti-inflammation, we study cytotoxicity effects of SHSR on Mouse Lung Fibroblast Cells and Peritoneal Macrophages, Inhibitory effects of SHSR on the nitric oxide (NO) release, the ROS production, and the interleukin-6 production. Results : The cytotoxicity of SHSR on mouse lung fibroblast Cells and Raw264.7 cell line was not observed. SHSR in RAW264.7 cell line inhibited $IL-1{\beta}$, IL-6 mRNA gene expression depending upon the concentrations of extract and inhibited IL-18 mRNA gene expression at 100 ${\mu}g/ml$ of extract. SHSR in RAW264.7 cell line inhibit COX-2 mRNA gene expression at 100, 10 ${\mu}g/ml$ of extract. SHSR in RAW264.7 cell line inhibited NOS-II mRNA gene expression depending upon the concentrations of extract. SHSR in RAW264.7 cell line didn't inhibit $TNF-{\alpha}$ mRNA gene expression. SHSR in RAW264.7 cell line decreased IL-6 production depending upon the concentrations of extract. SHSR in RAW264.7 cell line decreased $ITNF-{\alpha}$ production according to the concentrations of extract. SHSR in RAW264.7 cell line inhibited NO release specially SHSR 100, 10 ${\mu}g/ml$ concentrations of extract. SHSR inhibit ROS production depending upon the concentrations of extract. Conclusion : These results suggest that SHSR can be used treating a lot of women disease caused by inflammation.
Previously, we reported that Helicobacter pylori-associated gastritis and gastric cancer are closely associated with increased levels of hydrogen sulfide ($H_2S$) and that Korean red ginseng significantly reduced the severity of H. pylori-associated gastric diseases by attenuating $H_2S$ generation. Because the incubation of endothelial cells with $H_2S$ has been known to enhance their angiogenic activities, we hypothesized that the amelioration of $H_2S$-induced gastric inflammation or angiogenesis in human umbilical vascular endothelial cells (HUVECs) might explain the preventive effect of Korean red ginseng on H. pylori-associated carcinogenesis. The expression of inflammatory mediators, angiogenic growth factors, and angiogenic activities in the absence or presence of Korean red ginseng extracts (KRGE) were evaluated in HUVECs stimulated with the $H_2S$ generator sodium hydrogen sulfide (NaHS). KRGE efficiently decreased the expression of cystathionine ${\beta}$-synthase and cystathionine ${\gamma}$-lyase, enzymes that are essential for $H_2S$ synthesis. Concomitantly, a significant decrease in the expression of inflammatory mediators, including cyclooxygenase-2 and inducible nitric oxide synthase, and several angiogenic factors, including interleukin (IL)-8, hypoxia inducible factor-1a, vascular endothelial growth factor, IL-6, and matrix metalloproteinases, was observed; all of these factors are normally induced after NaHS. An in vitro angiogenesis assay demonstrated that NaHS significantly increased tube formation in endothelial cells, whereas KRGE pretreatment significantly attenuated tube formation. NaHS activated p38 and Akt, increasing the expression of angiogenic factors and the proliferation of HUVECs, whereas KRGE effectively abrogated this $H_2S$-activated angiogenesis and the increase in inflammatory mediators in vascular endothelial cells. In conclusion, KRGE was able to mitigate $H_2S$-induced angiogenesis, implying that antagonistic action against $H_2S$-induced angiogenesis may be the mechanism underlying the gastric cancer preventive effects of KRGE in H. pylori infection.
Bang, Chang Seok;Hong, So Hyung;Suk, Ki Tae;Kim, Jin Bong;Han, Sang Hak;Sung, Hotaik;Kim, Eun Ji;Kim, Myoung Jo;Kim, Moon Young;Baik, Soon Koo;Kim, Dong Joon
Journal of Ginseng Research
/
v.38
no.3
/
pp.167-172
/
2014
Background: Roles of immune reaction and toll-like receptor-4 (TLR-4) have widely been established in the pathogenesis of alcoholic liver disease (ALD). Methods: We evaluated the biologic efficacy of Korean Red Ginseng (KRG), urushiol, and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) in mouse models of ALD. Sixty C57BL/6 mice were equally divided into six feeding groups for 10 weeks: normal diet, alcohol, control, alcohol + KRG, alcohol + urushiol, and alcohol + probiotics. Alcohol was administered via a LiebereDeCarli liquid diet containing 10% alcohol. TLR-4 expression, proinflammatory cytokines, and histology, as well as the results of liver function tests were evaluated and compared. Results: No between-group differences were observed with regard to liver function. TLR-4 levels were significantly lower in the KRG, urushiol, and probiotics groups than in the alcohol group ($0.37{\pm}0.06ng/mL$, $0.39{\pm}0.12ng/mL$, and $0.33{\pm}0.07ng/mL$, respectively, vs. $0.88{\pm}0.31ng/mL$; p < 0.05). Interleukin-$1{\beta}$ levels in liver tissues were decreased among the probiotics and KRG groups. The tumor necrosis factor-${\alpha}$ level of liver tissue was decreased in the KRG group. Conclusion: The pathological findings showed that alcohol-induced steatosis was significantly reduced by KRG and urushiol. As these agents improve immunologic capacity, they may be considered in potential anti-ALD treatments.
Kim, Yejin;Kim, Hyemin;Bae, Seyeon;Choi, Jiwon;Lim, Sun Young;Lee, Naeun;Kong, Joo Myung;Hwang, Young-Il;Kang, Jae Seung;Lee, Wang Jae
IMMUNE NETWORK
/
v.13
no.2
/
pp.70-74
/
2013
L-ascorbic acid (vitamin C) is one of the well-known antiviral agents, especially to influenza virus. Since the in vivo antiviral effect is still controversial, we investigated whether vitamin C could regulate influenza virus infection in vivo by using Gulo (-/-) mice, which cannot synthesize vitamin C like humans. First, we found that vitamin C-insufficient Gulo (-/-) mice expired within 1 week after intranasal inoculation of influenza virus (H3N2/Hongkong). Viral titers in the lung of vitamin C-insufficient Gulo (-/-) mice were definitely increased but production of anti-viral cytokine, interferon (IFN)-${\alpha}/{\beta}$, was decreased. On the contrary, the infiltration of inflammatory cells into the lung and production of pro-inflammatory cytokines, tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-${\alpha}/{\beta}$, were increased in the lung. Taken together, vitamin C shows in vivo antiviral immune responses at the early time of infection, especially against influenza virus, through increased production of IFN-${\alpha}/{\beta}$.
Purpose : Investigate the effects of Haeganjeon water extract (HGJ) on immobilization-stress or cold-stress in C57BL/6J mice. Methods : Male C57BL/6J 30 mice of weighting 18${\pm}$2g, were divided into sixs groups including the immobilization-stress group(5heads), after immobilization-stress HGJ oral administration(500mg/kg) groups(5heads), cold-stress group(5heads) and after cold-stress HGJ oral administration(500mg/kg) groups(5heads). then we observed changes in the serum histamine and corticosterone level and changes immune system. Results : HGJ decreased the serum level of histamine and corticosterone increased by immobilization-stress or cold-stress. HGJ inhibited the release of histamine from mast cells. In addition, HGJ enhanced the cell viability of thymocytes decreased by immobilization-stress or cold-stress and decreased DNA fragmentation of thymocytes increased by immobilization- stress or cold-stress. Also, HGJ increased the cell viability of splenocytes decreased by cold-stress and decreased DNA fragmentation of splenocytes increased by cold-stress. HGJ decreased the population of thymic CD4+ cells increased by immobolization-stress. HGJ increased the population of B220+ cells decreased by immobilization-stress and decreased the population of Thy1+ cells increased by immobilization-stress. Also, HGJ decreased the population of splenic CD4+ cells increased by immobolization-stress. HGJ enhanced the production of ${\gamma}-interferon$ decreased by immobilization-stress or cold-stress and increased the production of interleukin-4 decreased by immobilization-stress. Furthermore, HGJ enhanced the phagocytic activity decreased by immobilization-stress or cold-stress and enhanced the level of nitric oxide decreased by immobilization-stress or cold-stress. Conclusion : HGJ may be useful for the prevention and treatment of stress via suppression of serum histamine and corticosterone level and enhancement of immune response.
The principal objective of this study was to compare the effects of whole and hydrolyzed cells (bifidobacteria) treated with gastrointestinal digestive enzymes on the activation of cloned macrophages. Seven different strains of Bifidobacterium obtained from swine, chickens, and rats, were digested with pepsin followed by pancreatin and the precipitate (insoluble fraction) and supernatant (soluble fraction) obtained via centrifugation. The RAW 264.7 murine macrophages were incubated with either whole cells, the precipitate, or supernatant at various concentrations. Pronounced increases in the levels of nitric oxide (NO), interleukin $(IL)-1{\beta}$, IL-6, IL-12, and tumor necrosis factor $(TNF)-{\alpha}$ were observed in the whole cells and precipitates, but these effects were less profound in the supernatants. The precipitates also evidenced a slight, but significant, inductive activity for NO and all tested cytokines, with the exception of $(TNF)-{\alpha}$ in the macrophage model as compared with the whole cells. By way of contrast, $(TNF)-{\alpha}$ production when cultured with whole cells (100 ng/ml) resulted in marked increases as compared with what was observed with the precipitates. The results of this study indicated, for the first time, that digested Bifidobacterium sp. can induce the production of NO and several cytokines in RAW 264.7 murine macrophage cells. In the current study, it was demonstrated that Bifidobacterium strains treated with digestive enzymes, as compared with whole cells, are capable of stimulating the induction of macrophage mediators, which reflects that they may be able to modulate the gastrointestinal immune functions of the host.
This experimental study was carried out to evaluate the effects of Kimchi intake of Cordyceps sinensis extract (CDSE) supplementation on cytokine-induction and immune response in mice. To study in experiments using male Balb/c mice fed Kimchi and Kimchi of CDSE supplementation (addition of 2% of total Kimchi weight) containing fed experimental diet during 2 weeks. Experimental mice were fed control diet or diet containing freeze-dried Kimchi at the level of 5%(w/w) or 5% freeze-dried Kimchi with 2% CDSE supplementation. The main ingredient of Kimchi was Korean cabbage and fermentation was carried out at $4^{\circ}C$ for three weeks. Freeze-dried 2% CDSE supplementation was added to Kimchi at the beginning of fennentation. In order to investigate the effect of Kimchi intake of CDSE supplementation (5%Kimchi-2%CDSE), the following was performed; body weight, food intake, hematological parameter, serum level of mouse interleukin-4 (mIL-4) and mouse $interferon-{\gamma}$$(mIFN-{\gamma})$, and, the percentage of CD3+/CD4+, CD3+/CD8+, B220+ in splenic cells. The results of final body weight, and food diet intake of two Kimchi groups were lower than those of the control group (not supplemented experimental diet). The hematology change obtained from the level of WBC (white blood cell) and platelet were not affected by feeding different dietary regiments, but the level of RBC (red blood cells) HB (hemoglobin), and spleen weight of two Kimchi groups were increased significantly than those of the control group. The serum level of IL-4 and $IFN-{\gamma}$ of two Kimchi groups were increased significantly than those of the control group, also enhanced the percentages of the CD3+/CD4+ and CD3+/CD8+ by 5% freeze-dried Kimchi, and 5%Kimchi-2%CDSE group were 43.9 and 60.1%, and 96.0 and 174% than those of the control group, respectively. From these results, it can be concluded that Kimchi itself has an immuno-stimulatory effect and Kimchi contaning 2% CDSE supplementation has the more pronounced effect in vivo system.
Natural killer (NK) cells provide one of the initial barriers of cellular host defense against pathogens, in particular intracellular pathogens. Because bone marrow-derived hematopoietic stem cells (HSCs), lymphoid protenitors, can give rise to NK cells, NK ontogeny has been considered to be exclusively lymphoid. Here, we show that porcine c-$kit^+$ bone marrow cells (c-$kit^+$ BM cells) develop into NK cells in vitro in the presence of various cytokines [interleukin (IL)-2, IL-7, IL-15, IL-21, stem cell factor (SCF), and fms-like tyrosine kinase-3 ligand (FLT3L)]. Adding hydrocortisone (HDC) and stromal cells greatly increases the frequency of c-$kit^+$ BM cells that give rise to $CD2^+CD8^+$ NK cells. Also, intracellular levels of perforin, granzyme B, and NKG2D were determined by RT-PCR and western blotting analysis. It was found that of perforin, granzyme B, and NKG2D levels significantly were increased in cytokine-stimulated c-$kit^+$ BM cells than those of controls. And, we compared the ability of the cytotoxicity of $CD2^+CD8^+$ NK cells differentiated by cytokines from c-$kit^+$ BM cells against K562 target cells for 28 days. Cytokines-induced NK cells as effector cells were incubated with K562 cells as target in a ratio of 100 : 1 for 4 h once a week. In results, $CD2^+CD8^+$ NK cells induced by cytokines and stromal cells showed a significantly increased cytotoxicity 21 days later. Whereas, our results indicated that c-$kit^+$ BM cells not pretreated with cytokines have lower levels of cytotoxicity. Taken together, this study suggests that cytokines-induced NK cells from porcine c-$kit^+$ BM cells may be used as adoptive transfer therapy if the known obstacles to xenografting (e.g. immune and non-immune problems) were overcome in the future.
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