• Journal of the Korea Academia-Industrial cooperation Society
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• v.15 no.11
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• pp.6739-6745
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• 2014

Acer tegmentosum Maxim (AT) is a species of the maple genus, which is native to North-Eastern China and Korea. Traditionally, AT has been already used for pain relief in Korea. On the other hand, its antidepressant-like activity and related molecular mechanisms is not completely understood. Using the Forced Swimming Test (FST), the effects of a subacute treatment with AT(100, 200, and 400 mg/kg, p.o.) on the immobility and FST-induced changes to the immune parameters, cortisol, ACTH, and cytokine, in rats were investigated. The tendency of immobility showed a dose-dependent decrease in FST. The levels of cortisol, IL-6 and $IL-1{\beta}$ in the peripheral blood were increased significantly after FST exposure. Overall, these results suggest that AT treatment can decrease the immobility time and the release of pro-inflammatory cytokines in the FST, suggesting that the anti-inflammatory effects of AT might be involved in the antidepressant-like effect.

• The Journal of Korean Medicine
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• v.39 no.2
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• pp.92-105
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• 2018

Objectives: This aim of this study is to compare the reflux esophagitis improvement effects of Sepiae Os, Arcae Concha, Ostreae Concha, and Proton Pump Inhibitor(esomeprazole) through rat experiments. Methods: NO production inhibitory effect was measured by NO production amount and iNOS mRNA expression level in cell lines. iNOS, $TNF-{\alpha}$ and $p-I{\kappa}B$, and serotonin were compared using immunohistochemistry at the rat reflux esophagitis. Reflux esophagitis connection external form, lower esophageal sphincter, and gap were observed and an esophageal inflammatory indicator, IL-6 activity was also evaluated by immunohistochemistry. Results: NO production and iNOS mRNA expression was showed concentration dependent decrease in cell lines treated with Sepiae OS, Arcae Concha, and Ostreae Concha at the experiments of cell lines. In the suppression of iNOS and $p-I{\kappa}B$ at the rat reflux esophagitis, Sepiae Os treat group(SOT) and Ostreae Concha treat group(OCT) were more effective. In the increase of serotonin at the rat reflux esophagitis, ACT, MT and OCT were more effective. Damage of lower esophageal sphincter, and gap between esophageal keratin and mucosa were observed less at the SOT, ACT, OCT. In the suppression of IL-6 at the rat reflux esophagitis, SOT and OCT were more effective than GE and, SOT was more effective than MT significantly. Conclusions: The anti-inflammatory effect was the best in the SOT and lower esophageal sphincter muscle contraction was the best in the ACT at the rat reflux esophagitis. Sepiae OS was more effective than esomeprazole in the suppression of iNOS, $TNF-{\alpha}$, and IL-6.

• Journal of Ginseng Research
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• v.42 no.1
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• pp.68-74
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• 2018

Background: Ginsenosides have been reported to have many health benefits, including anti-inflammatory effects, and the resolution of inflammation is now considered to be an active process driven by M2-type macrophages. In order to determine whether ginsenosides modulate macrophage phenotypes to reduce inflammation, 11 ginsenosides were studied with respect to macrophage polarization and the resolution of inflammation. Methods: Mouse peritoneal macrophages were polarized into M1 or M2 phenotypes. Reverse transcription-polymerase chain reaction, Western blotting, and measurement of nitric oxide (NO) and prostaglandin $E_2$ levels were performed in vitro and in a zymosan-induced peritonitis C57BL/6 mouse model. Results: Ginsenoside $Rg_3$ was identified as a proresolving ginseng compound based on the induction of M2 macrophage polarization. Ginsenoside $Rg_3$ not only induced the expression of arginase-1 (a representative M2 marker gene), but also suppressed M1 marker genes, such as inducible NO synthase, and NO levels. The proresolving activity of ginsenoside $Rg_3$ was also observed in vivo in a zymosan-induced peritonitis model. Ginsenoside $Rg_3$ accelerated the resolution process when administered at peak inflammatory response into the peritoneal cavity. Conclusion: These results suggest that ginsenoside $Rg_3$ induces the M2 polarization of macrophages and accelerates the resolution of inflammation. This finding opens a new avenue in ginseng pharmacology.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.71-76
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• 2010

Skin irritation caused by retinol and retinoic acid results in mild erythema called as retinoid dermatitis. To develop compounds modulating the retinoid dermatitis, we tried to establish the screening method for retinoid dermatitis. At first we examined the inflammatory cytokine profile in neonatal human dermal fibroblasts which are known to be one of main site of retinoid action. As a result, interleukin-8 (IL-8) and monocytes chemoattractant protein-1 (MCP-1) were significantly produced by all trans retinoic acid (ATRA) and all trans retinol (ATROL) in dermal fibroblasts. Especially the production of MCP-1 was more than that of IL-8. The production of MCP-1 by retinoid was dose-dependently increased, continuing up to 24 hrs. After then using ethacrynic acid (ECA) known to reduce mouse ear edema induced by ATRA, we checked whether ECA suppressed the production of MCP-1. As a result, ECA effectively suppressed the production of MCP-1 in the ATRA- or ATROL-treated-fibroblasts. These results suggested that screening method effectively reflects the in vivo anti-inflammatory activity of ECA. It was reported that citral inhibited the enzyme involved in the conversion of ATROL to ATRA. We showed that citral suppressed the production of MCP-1 in ATROL-treated fibroblasts. We expect these finding might be helpful to find useful compounds modulating the side effects of retinoid or retinoid dermatitis.

• The Journal of the Korean Society for Microbiology
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• v.35 no.1
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• pp.9-18
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• 2000

Immunological mechanisms involving the release of inflammatory factors by HIV-1 infected microglia in the brain have been implicated in the pathogenesis of HIV dementia (HIVD). Since the regulation of matrix metalloproteinases (MMPs) activity can be influenced by variety of inflammatory mediators, this study was undertaken to look for a correlation between the MMP-9 release and the production of TNF-${\alpha}$ in response to HIV-1 p24 in the human monocyte cell line THP-1 as a model for microglia. First, it was shown that HIV-l core p24 antigen induced THP-1 to secrete MMP-9 in a dose response manner while it elicited a little effect on MMP-2 release in human astroglial cell line T98G. Next, it was found that p24 induced THP-1 to secrete TNF-${\alpha}$ without prior differentiation into macrophages by phorbol myristate acetate (PMA) treatment. Furthermore, anti-TNF-${\alpha}$ neutralizing antibodies significantly blocked p24-induced MMP-9 release in a dose dependent manner. Our data indicate that p24 antigen induces monocytic MMP-9 release by triggering up-regulation of TNF-${\alpha}$ secretion.

• Herbal Formula Science
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• v.11 no.1
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• pp.115-128
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• 2003

Bojungikgitang is the water extracts prepared from Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Astractylodis Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Bupleuri Radix, Cimicifugae Rhizoma, which has been used for the treatment of indigestion, and immunological disease in oriental countries. In this study, the effects of Bojungikgitang on the productions of nitiric oxide (NO) and prostaglandin $E_2\;(PGE_2)$, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined using RAW 264.7 macrophages activated with $interferon-{\gamma}\;(IFN-{\gamma})$ plus lipopolysaccharide (LPS). Bojungikgitang (10-400 ${\mu}$g/ml) per se had no cytotoxic effect in unstimulated macrophages, but this compound dose-dependently reduced the release of NO and $PGE_2$ caused by stimulation of $LPS/IFN-{\gamma}$. The levels of iNOS and COX-2 protein were markedly suppressed by the treatment with Bojungikgitang in a concentration dependent manner. Moreover, Bojungikgitang also attenuated the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (1L)-1${\beta}$ and IL-6 in LPS-stimulated RAW 264.7 macrophages. These results suggest that Bojungikgitang decreases the NO and $PGE_2$ production in macrophages by inhibiting iNOS and COX-2 expression and these properties may contribute to the anti-inflammatory activity of Bojungikgitang.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.27-34
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• 2014

Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin $D_2$ ($PGD_2$) and 5-lipoxygenase (5-LO) dependent leukotriene $C_4$ ($LTC_4$) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular $Ca^{2+}$ influx via phospholipase $C{\gamma}1$ ($PLC{\gamma}1$) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-${\kappa}B$ (NF-${\kappa}B$) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum $LTC_4$, $PGD_2$, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.

• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.66-71
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• 2013

Broussonetia papyrifera and Lonicera japonica have long been used in the treatment of inflammatory disorders in Chinese medicine, especially respiratory inflammation. Previously, a new phytoformula (BL) containing B. papyrifera and L. japonica was found to exert strong anti-inflammatory activity against several animal models of inflammation, especially against an animal model of acute bronchitis. In the present investigation, the effects of BL on animal models of septic inflammation and chronic bronchitis are examined. Against lipopolysaccharide (LPS)-induced septic inflammation in mice, BL (200-400 mg/kg) reduced the induction of some important proinflammatory cytokines. At 1 h after LPS treatment, BL was found to considerably inhibit TNF-${\alpha}$ production when measured by cytokine array. At 3 h after LPS treatment, BL inhibited the induction of several proinflammatory cytokines, including IFN-${\gamma}$ and IL-$1{\beta}$, although dexamethasone, which was used as a reference, showed a higher inhibitory action on these biomarkers. Against chronic bronchitis induced by LPS/elastase instillation in rats for 4 weeks, BL (200-400 mg/kg/day) significantly inhibited cell recruitment in bronchoalveolar lavage fluid. Furthermore, BL considerably reduced lung injury, as revealed by histological observation. Taken together, these results indicate that BL may have a potential to treat systemic septic inflammation as well as chronic bronchitis.

• Biomolecules & Therapeutics
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• v.20 no.6
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• pp.526-531
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• 2012

During our on-going studies to identify bioactive compounds in medicinal herbs, we found that saucerneol F (SF), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis), showed in vitro anti-inflammatory activity. In this study, we examined the effects of SF on the generation of 5-lipoxygenase (5-LO) dependent leukotriene $C_4$ ($LTC_4$), cyclooxygenase-2 (COX-2) dependent prostaglandin $D_2$ ($PGD_2$), and on phospholipase $C{\gamma}1$ ($PLC{\gamma}1$)-mediated degranulation in SCF-induced mouse bone marrow-derived mast cells (BMMCs). SF inhibited eicosanoid ($PGD_2$ and $LTC_4$) generation and degranulation dose-dependently. To identify the molecular mechanisms underlying the inhibition of eicosanoid generation and degranulation by SF, we examined the effects of SF on the phosphorylation of $PLC{\gamma}1$, intracellular $Ca^{2+}$ influx, the translocation of cytosolic phospholipase $A_2$ ($cPLA_2$) and 5-LO, and on the phosphorylation of MAP kinases (MAPKs). SF was found to reduce intracellular $Ca^{2+}$ influx by inhibiting $PLC{\gamma}1$ phosphorylation and suppressing the nuclear translocations of $cPLA_2$ and 5-LO via the phosphorylations of MAPKs, including extracellular signal-regulated protein kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Taken together, these results suggest that SF may be useful for regulating mast cell-mediated inflammatory responses by inhibiting degranulation and eicosanoid generation.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.421-427
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• 2015

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene $C_4$ ($LTC_4$) and prostaglandin $D_2$ ($PGD_2$) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent $LTC_4$ and cyclooxygenase-2-dependent $PGD_2$ through the inhibition of intracellular calcium influx/phospholipase $C{\gamma}1$, cytosolic phospholipase $A_2$/mitogen-activated protein kinases and/or nuclear factor-${\kappa}B$ pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.