Retraction: Sasa borealis extract exerts an antidiabetic effect via activation of the AMP-activated protein kinase.

[This retracts the article on p. 15 in vol. 7, PMID: 23423690.].

Anti-inflammatory Effects of Sanguisorbae Radix on Contact Dermatitis Induced by Dinitrofluorobenzene in Mice.

OBJECTIVE: To investigate the anti-inflflammatory effects of Sanguisorbae Radix on contact dermatitis (CD). METHODS: Mice were sensitized by painting 30 µL of 1-fluoro-2,4-dinitrofluorobenzene (DNFB) onto each ear for 3 days. Four days later, mice were challenged by painting with 50 µL of DNFB onto the shaved dorsum every 2 days. Sanguisorbae Radix methanol extract (MESR) was applied onto the shaved dorsum every 2 days. The effects of MESR on skin thickness, skin weights, histopathological changes, skin lesions and cytokine production in DNFB-induced CD mice were investigated, as well as its effects on body weights and spleen/body weight ratio. RESULTS: Topical application of MESR effectively inhibited enlargement of skin thickness and weight (P<0.05). MESR treatment also inhibited hyperplasia, spongiosis and immune cell infiltration induced by DNFB in inflamed tissues and improved lesions on dorsum skin in CD mice. Moreover, treatment with MESR suppressed the increase in the levels of tumor necrosis factor α (TNF-α,P<0.01) and interferon γ (IFN-γ,P<0.05), respectively. Finally, MESR had no effect on body weight gain or spleen/body weight ratio. CONCLUSION: These data suggest that MESR acts as an anti-inflflammatory agent that decreases the production of TNF-α and IFN-γ, resulting in reductions of skin lesions and histopathological changes in inflamed skin tissues.

Therapeutic properties of Scutellaria baicalensis in db/db mice evaluated using Connectivity Map and network pharmacology.

We have reported that an extract of Scutellaria baicalensis (ESB) has effects against obesity and hypertriglyceridemia in type 2 diabetic animal model (db/db mouse). In the present study, we tried to explain the pharmacological effects of ESB by integrating gene expression information from db/db mouse liver with that of ESB-treated HepG2 hepatocellular carcinoma cells. Using Connectivity Map (cmap) analysis, we found an inverse relationship in the pharmaceutical profiles based on gene expression between db/db mouse liver and ESB-treated HepG2 cells. This inverse relationship between the two data sets was also observed for pathway activities. Functional network analysis showed that biological functions associated with diabetes and lipid metabolism were commonly enriched in both data sets. We also observed a similarity in distribution of cmap enrichment scores between db/db mouse liver and human diabetic liver, whereas there was an inverse pattern of cmap enrichment scores in human diabetic liver compared with ESB-treated HepG2 cells. This relationship might explain the pharmacological activities of ESB against db/db mouse and possible effectiveness of ESB against human diabetes. We expect that our approach using in vitro cell lines could be applied in predicting the pharmacological effectiveness of herbal drugs in in vivo systems.

Anti-Inflammatory Effects of Artemisia Leaf Extract in Mice with Contact Dermatitis In Vitro and In Vivo.

The leaves of Artemisia argyi Lev. et Vant. and A. princeps Pamp. are well known medicinal herbs used to treat patients in China, Japan, and Korea with skin problems such as eczema and itching, as well as abdominal pain and dysmenorrhoea. We investigated the anti-inflammatory effects of Artemisia leaf extract (ALE) using CD mice and Raw 264.7 cells. The effects of ALE on histopathological changes and cytokine production in ear tissues were assessed in mice with CD induced by 1-fluoro-2,4-dinitrobenzene (DNFB). Moreover, the anti-inflammatory effects on production levels of prostaglandin E2 (PGE2) and nitric oxide (NO) and expression levels of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) were investigated in Raw 264.7 cells. Topical application of ALE effectively prevented ear swelling induced by repeated DNFB application. ALE prevented epidermal hyperplasia and infiltration of immune cells and lowered the production of interferon- (IFN-) gamma (γ), tumour necrosis factor- (TNF-) alpha (α), and interleukin- (IL-) 6 in inflamed tissues. In addition, ALE inhibited expression of COX-2 and iNOS and production of NO and PGE2 in Raw 264.7 cells. These results indicate that Artemisia leaf can be used as a therapeutic agent for inflammatory skin diseases and that its anti-inflammatory effects are closely related to the inhibition of inflammatory mediator release from macrophages and inflammatory cytokine production in inflamed tissues.

Effects of astaxanthin on dinitrofluorobenzene-induced contact dermatitis in mice.

Astaxanthin (AST) is known to exhibit antioxidative and antitumor properties, therefore, the present study investigated its other potential medical applications. AST was observed to exhibit anti­allergic and anti­inflammatory effects in a dinitrofluorobenzene (DNFB)­induced contact dermatitis (CD) mouse model and RBL­2H3 cell lines. The topical application of AST effectively inhibited the enlargement of ear thickness and increase in weight, which occurred following repeated application of DNFB. Furthermore, topical application of different concentrations of AST inhibited inflammatory hyperplasia, edema, spongiosis, and the infiltration of mononuclear cells and mast cells in the ear tissue. In addition, the levels of TNF­α and IFN­Î³ produced were decreased by application of AST in vivo, and treatment of RBL­2H3 cells with AST inhibited the release of histamine and ß­hexosaminidase in vitro. Taken together, these data suggested that AST may be used to treat patients with allergic skin diseases through a mechanism, which may be associated with that involved in anti­inflammatory or anti-allergic activities.

[Genome wide expression analysis of the effect of Socheongryong Tang in asthma model of mice].

OBJECTIVE: To investigate the molecular effect of Socheongryong Tang (SCRT, Xiaoqinglong Tang in Chinese) on whole genome level in asthma mouse model by microarray technology. METHODS: Asthma was induced by intranasal instillation of ovalbumin in mouse. After administration of SCRT on asthma-induced mouse, the expression of genes in lung tissue was measured using whole genome microarray. The functional implication of differentially expressed genes was performed using ontological analysis and the similarity of promoter structure of genes was also analyzed. RESULTS: Treatment of SCRT restored expression level of many up- or down-regulated genes in asth- ma model, and this recovery rate means SCRT could regulate a set of genes having specific TFBS binding sites. CONCLUSION: In this study, we identified a set of genes subjected to similar regulation by SCRT in asthma model in mice.

Effects of Pogostemon cablin Blanco extract on hypoxia induced rabbit cardiomyocyte injury.

BACKGROUND: Pogostemonis Herba, the dried aerial part of Pogostemon cablin Blanco, is a well-known materia medica in Asia that is widely used for syndrome of gastrointestinal dysfunctions. OBJECTIVE: This study was undertaken to examine whether Pogostemon cablin extract (PCe) might have any beneficial effect on hypoxia induced rabbit cardiomyocyte injury. MATERIALS AND METHODS: Isolated cardiomyocytes were divided into three groups and the changes of cell viability in cardiomyocytes of hypoxic and hypoxia/reoxygenation group were determined. The effect of PCe on reactive oxygen species (ROS) generation, intracellular formation of ROS was also measured by monitoring the 2',7'-dichlorofluorescein fluorescence. RESULTS: PCe effectively protected the cells against both the hypoxia and reoxygenation induced injury, and the protective effect of PCe is not mediated by interaction with adenosine triphosphate-sensitive K(+) channels. In the presence of PCe, production of ROS under chemical hypoxia was remarkably reduced which suggests that PCe might exert its effect as a ROS scavenger. CONCLUSION: The present study provides clear evidence for the beneficial effect of PCe on cardiomyocyte injury during hypoxia or reoxygenation following prolonged hypoxia.

Effects of Valerianae Radix et Rhizoma extract on psychological stress in mice.

BACKGROUND: The aim of this study was to identify the effects of Valerianae Radix et Rhizoma water extract (VRe) originated from Valeriana fauriei Briquet on reducing psychological stress (PS) on mice. OBJECTIVE: Mice were put under PS with communication box method: Restraining mice and forcing to see other mice underfoot shock stress. MATERIALS AND METHODS: Measurements on plasma corticosterone, noradrenaline and lipid peroxidation, and elevated plus-maze (EPM) tests were carried out to determine the effect of VRe administration on physiological and behavioral responses of mice. RESULTS: VRe showed anxiolytic effects in plasma corticosterone, noradrenaline, and EPM transfer latency levels, but it did not show any significant effects on the other indicators. CONCLUSION: V. fauriei, which has been used as a natural anxiolytic drug, exerts positive effects in the communication box induced PS in mice.

Effect of co-administration of Angelicae gigantis radix and Lithospermi radix on rat hepatic injury induced by carbon tetrachloride.

BACKGROUND: Co-administration of Angelicae gigantis radix (AGR) and Lithospermi radix (LR) has been commonly applied to patients to treat cardiac and hepatic disorders. Individual bioactivities of these herbal medicines have been widely investigated, but the hepatoprotective effects of co-treatment of AGR and LR have yet to be clarified. OBJECTIVE: The present study investigated the protective effects of extracts of AGR and LR on carbon tetrachloride (CCl4) induced hepatic injury. MATERIALS AND METHODS: In this study, we measured the hepatoprotective activity of individual and co-treatment of the two herbal medicines on hepatic injury induced by CCl4 by measuring different biochemical parameters such as serum aspartate aminotransaminase (AST) and serum alanine aminotransaminase (ALT). Microarray technology also used to compare ontological difference with individual and co-treatment of these two. RESULTS: Combined treatment with AGR and LR (AGR + LR) decreased AST and ALT level in serum which demonstrate hepatoprotective effect of the therapy. When the effect of AGR and LR according to treatment conditions was measured, co-treatment showed the most prominent effect on hepatic injury by CCl4 rather than individual treatment condition. We further defined gene set that could be the molecular target of herbal effect on hepatic injury by CCl4 using bioinformatical analysis of interaction network. Highly recovered genes by treating AGR + LR play significant roles in response to hepatic injury induced by CCl4. CONCLUSION: Combined treatment with AGR and LR showed synergistic protective effects on the CCl4-induced rat hepatic tissue injury.

Effects of Dictamnus dasycarpus Turcz., root bark on ICAM-1 expression and chemokine productions in vivo and vitro study.

ETHNOPHARMACOLOGICAL RELEVANCE: The root bark of Dictamnus dasycarpus Turcz., family Rutaceae is a well known anti-inflammatory agent for skin diseases such as eczema, pruritus and urticaria in Eastern countries. MATERIALS AND METHODS: We investigated the effects of methanol extract of Dictamnus dasycarpus root bark (MEDD) on Intercellular Adhesion Molecule-1 (ICAM-1) expression, epidermal hyperplasia and immune cell infiltration in 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis (CD) mice. We also investigated its effects on the expression of ICAM-1, binding capacity to THP-1 cells, cytokine and chemokine production, and phosphorylation of NF-κB in human keratinocytes (HaCaT cells). RESULTS: Topical application of MEDD effectively inhibited ICAM-1 expression and epidermal hyperplasia in inflamed tissues. MEDD treatment also inhibited immune cell infiltration induced by DNFB. In addition, treatment with MEDD reduced surface expression and total amount of ICAM-1in HaCaT cells and effectively lowered the capacity to bind to THP-1 cells. MEDD also lowered the levels of IL-6, IL-8, monokine induced by gamma interferon (MIG), monocyte chemotactic protein-1 (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES). Finally, MEDD treatment prevented activation of the NF-κB pathway induced by TNF-α in HaCaT cells. CONCLUSIONS: These data indicate that root bark of Dictamnus dasycarpus has the potential for treatment of inflammatory skin diseases as a complementary or alternative medicine to corticosteroids. In addition, they suggest that the anti-inflammatory effects of Dictamnus dasycarpus on CD are involved in the regulation of ICAM-1 expression and cytokine and chemokine secretion through down-regulation of the NF-κB signaling pathway in keratinocytes.

Comparative study of Korean White Ginseng and Korean Red Ginseng on efficacies of OVA-induced asthma model in mice.

BACKGROUND: Korean ginseng is a well-known medicinal herb that has been widely used in traditional medicine to treat various diseases, including asthma. Ginseng can be classified as white ginseng (WG) or red ginseng (RG), according to processing conditions. In this study, the authors compared the efficacies of these two ginseng types in a mouse model of acute asthma. METHODS: To produce the acute asthma model, BALB/c mice were sensitized with ovalbumin (OVA) and aluminum hydroxide, and then challenged with OVA. WG and RG extracts were administered to mice orally. The influences of WG and RG on airway hyperresponsiveness (AHR), immune cell distributions in bronchoalveolar lavage fluid (BALF), and OVA-specific immunoglobulin E (IgE), IgG1, and IgG2a in serum were investigated. Cytokine production by lymphocytes isolated from peribronchial lymph nodes and histopathological changes was also examined. RESULTS: In OVA-sensitized mice, both WG and RG reduced AHR and suppressed immune cell infiltration in bronchoalveolar regions. BALF OVA-specific IgE levels were significantly lower in RG-treated OVA-sensitized mice than in the OVA-sensitized control group. WG and RG also suppressed inflammatory cytokine production by peribronchial lymphocytes. Histopathological findings showed reduced inflammatory cell infiltration and airway remodeling (e.g., epithelial hyperplasia) in WG- and RG-treated OVA mice compared with OVA controls. CONCLUSION: In this study, WG and RG showed antiasthmatic effects in an OVA-sensitized mouse model, and the efficacies of RG were found to be better than those of WG.

So-Cheong-Ryong-Tang, a herbal medicine, modulates inflammatory cell infiltration and prevents airway remodeling via regulation of interleukin-17 and GM-CSF in allergic asthma in mice.

BACKGROUND: So-Cheong-Ryong-Tang (SCRT), herbal medicine, has been used for the control of respiratory disease in East Asian countries. However, its therapeutic mechanisms, especially an inhibitory effect on inflammatory cell infiltration and airway remodeling in allergic asthma are unclear. OBJECTIVE: The present study investigated the mechanism of antiasthmatic effects of SCRT in allergic asthma in mice. MATERIALS AND METHODS: We investigated the influence of SCRT on levels of interleukin-17 (IL-17), granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-4, and interferon gamma (IFN-γ) in bronchoalveolar lavage fluid (BALF), ovalbumin (OVA)-specific IgE in serum, and histopathological changes in allergen-induced asthma. RESULTS: So-Cheong-Ryong-Tang decreased levels of IL-17 and GM-CSF in BALF. IL-4, a Th2-driven cytokine, was also decreased by SCRT, but IFN-γ, a Th1-driven cytokine, was not changed. Levels of OVA-specific IgE in serum were also decreased by SCRT. With SCRT treatment, histopathological findings showed reduced tendency of inflammatory cell infiltration, and prevention from airway remodeling such as epithelial hyperplasia. CONCLUSION: In this study, we firstly demonstrated that regulation of IL-17 and GM-CSF production may be one of the mechanism contributed to a reduction of inflammatory cell infiltration and prevention from airway remodeling.

Anti-inflammatory effects of Cryptotympana atrata Fabricius slough shed on contact dermatitis induced by dinitrofluorobenzene in mice.

BACKGROUND: The slough shed of Cryptotympana atrata Fabricius is widely used to treat skin diseases in China, Japan, and Korea. OBJECTIVE: To investigate the anti-inflammatory effects of C. atrata on contact dermatitis. MATERIALS AND METHODS: We investigated the effects of C. atrata methanol extract (MECA) on ear swelling, histophathological changes and cytokine production in 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis (CD) mice. RESULTS: Topical application of MECA effectively inhibited enlargement of ear swelling (30 and 100 µ/ear, P < 0.05; 300 µg/ear, P < 0.01). MECA treatment also inhibited hyperplasia, spongiosis (100 and 300 µg/ear, P < 0.001), and immune cell infiltration (30 µg/ear, P < 0.05; 100 and 300 µg/ear, P < 0.001) induced by DNFB. In addition, treatment with MECA suppressed the increase in the levels of TNF-α (P < 0.05), IFN-g (3, 100 µg/ear, P < 0.05; 300 µg/ear, P < 0.01), and IL-6 (100 µg/ear, P < 0.05; 300 µg/ear, P < 0.01) production. CONCLUSION: These data suggest that MECA has the potential for use in the treatment of inflammatory skin diseases, including CD. Moreover, the results presented herein indicate that anti-inflammatory actions of MECA are mediated by decreasing production of TNF-α, IFN-γ, and IL-6 in inflamed tissues.

Antiasthmatic effects of schizandrae fructus extract in mice with asthma.

BACKGROUND: Schizandrae fructus (SF), the fruit of Schisandra chinensis, has been used for the treatment of cough, wheezing, dry mouth, hepatitis, cardiovascular disease, and as a tonic and astringent in China, Japan, and Korea. OBJECTIVE: Investigation of the antiasthmatic effects of SF. MATERIALS AND METHODS: We investigated the effects of SF on airway hyperresponsiveness (AHR) to methacholine, production levels of antigen-specific antibodies, and histopathological changes in the lung tissue in a mouse model (Balb/c) of asthma induced by repeated intranasal instillation of an antigen. RESULTS: SF lowered AHR to methacholine (P < 0.05), antigen-specific immunoglobulin E (IgE) level (P < 0.01), and immune cell infiltration in mice with asthma. Prednisolone (PD) effectively decreased AHR (P < 0.01), total antibody (P < 0.01) and IgE (P < 0.01) levels, and immune cell infiltration. SF and PD did not affect the levels of antigen-specific IgG1 and IgG2a antibodies. CONCLUSION: Our data suggest that SF has possible application as an antiasthmatic drug. We also suggest that SF could be used as a complementary or alternative medicine to glucocorticoids.

Anti-inflammatory activities of Dictamnus dasycarpus Turcz., root bark on allergic contact dermatitis induced by dinitrofluorobenzene in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The root bark of Dictamnus dasycarpus Turcz. is widely used as a medicinal herb for treatment of skin diseases such as eczema, pruritus and urticaria in China, Japan and Korea. MATERIALS AND METHODS: We investigated the effects of methanol extract of Dictamnus dasycarpus Turcz., root bark (MEDD) on ear thickness, ear weights, histopathological changes such as hyperplasia, edema, spongiosis and immune cell infiltration and cytokine productions in 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis (CD) mice. We also investigated its effects on degranulation of histamine and ß-hexosaminidase and related mechanisms using RBL-2H3 cells. RESULTS: Topical application of MEDD effectively inhibited enlargement of ear thickness and weight (P<0.05). MEDD treatment also inhibited hyperplasia, edema and spongiosis induced by DNFB. Treatment with 300 µg/ear of MEDD suppressed the increase in IFN-γ and TNF-α levels (P<0.05). In addition, treatment with >50 µg/mL MEDD reduced the level of ß-hexosaminidase release, while >100 µg/mL MEDD lowered the level of histamine release in a dose-dependent manner (P<0.05). Finally, MEDD treatment prevented phosphorylation of p38 MAPK induced by phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 in RBL-2H3 cells. CONCLUSIONS: These data indicate that root bark of Dictamnus dasycarpus Turcz. has the potential for use in the treatment of allergic skin diseases. Furthermore, they suggest that root bark of Dictamnus dasycarpus Turcz. is involved in decreasing degranulation of MCs via inhibition of the p38 MAPK pathway as well as in the inhibition of Th1 skewing reactions.

Antiobesity activity of Vigna nakashimae extract in high-fat diet-induced obesity.

In this study, we evaluated the antiobesity effects of Vigna nakashimae (VN) extract and elucidated the underlying mechanisms. VN extract suppressed adipocyte differentiation and significantly attenuated the expression of adipogenic genes in 3T3-L1 cells. It decreased the expression of peroxisome proliferator-activated receptor γ (PPARγ) and its target genes in fully differentiated 3T3-L1 cells. Moreover, it enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC), and increased the expression of fatty acid oxidation genes. In high-fat diet (HFD) fed mice, VN extract suppressed HFD-induced increases in body weight, epididymal fat tissue weight, and hepatic lipid levels, and decreased the plasma levels of triacylglycerols, fatty acid, total cholesterol, and inflammatory cytokines. Consistently with in vitro study results, VN extract prevented HFD-induced increases in the expression of PPARγ and its target genes, and restored the decrease in the phosphorylation of AMPK and ACC in epididymal fat and liver tissues. These findings suggest that Vigna nakashimae prevents obesity through suppression of PPARγ expression and activation of AMPK, and that it might be a useful dietary supplement for the prevention of obesity.

Sasa borealis extract exerts an antidiabetic effect via activation of the AMP-activated protein kinase.

Leaf of Sasa borealis, a species of bamboo, has been reported to exhibit anti-hyperglycemic effect. However, its antidiabetic mechanism is not fully understood. In this study, we examined whether an extract of S. borealis activates AMP-activated protein kinase (AMPK) and exerts anti-hyperglycemic effects. Treatment with the S. borealis extract increased insulin signaling and phosphorylation of AMPK and stimulated the expression of its downstream targets, including PPARα, ACO, and CPT-1 in C2C12 cells and PPARα in HepG2 cells. However, inhibition of AMPK activation attenuated insulin signaling and prevented the stimulation of AMPK target genes. The S. borealis extract increased glucose uptake in C2C12 cells and suppressed expression of the gluconeogenic gene, PEPCK in HepG2 cells. The extract significantly reduced blood glucose and triglyceride levels in STZ-induced diabetic mice. The extract enhanced AMPK phosphorylation and increased Glut-4 expression in the skeletal muscle of the mice. These findings demonstrated that the S. borealis extract exerts its anti-hyperglycemic effect through activation of AMPK and enhancement of insulin signaling.

Effect of Sophora flavescens Aiton extract on degranulation of mast cells and contact dermatitis induced by dinitrofluorobenzene in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried root of Sophora flavescens Aiton (Sophorae radix, SR) has long been used in traditional medicine for the treatment of fever and swelling in eastern countries. MATERIALS AND METHODS: The present study investigated the anti-allergic and anti-inflammatory effects of SR using 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis mouse model and in vitro using RBL-2H3 cells. RESULTS: In mice, the topical application of 10 mg/mL of SR effectively inhibited enlargement of ear thickness and weight induced by repeated painting with DNFB. Topical application of SR also inhibited hyperplasia, edema, spongiosis and infiltration of mononuclear cells in ear tissue. In addition, production levels of interferon-gamma and tumor necrosis factor-alpha were decreased by SR in vivo. Finally, the release of histamine and ß-hexosaminidase, and migration were inhibited by treatment with SR. CONCLUSIONS: These data indicate the potential of SR in treating patients with allergic skin diseases and also suggest that related mechanisms are involved in anti-inflammatory action on the Th 1 skewing reaction and inhibition against recruitment and degranulation of mast cells.

Dangkwisoo-san, an herbal medicinal formula, ameliorates acute lung inflammation via activation of Nrf2 and suppression of NF-κB.

ETHNOPHARMACOLOGICAL RELEVANCE: Dangkwisoo-san (DS), an herbal medicinal formula, has long been used in Korea for the treatment of inflammatory complications caused by physical trauma. Although the therapeutic effect of DS is likely associated with anti-inflammatory activity, the precise underlying mechanisms are largely unknown. Here we sought to elucidate the possible mechanisms of anti-inflammatory activity of DS. MATERIALS AND METHODS: The water extract of DS was orally fed to C57BL/6 mice for 14 days prior to LPS intranasal instillation for lung inflammation. The effects of DS on lung inflammation were determined by differential cell counting, lung histology, and semi-quantitative RT-PCR of lung sections. The effects of DS on the activities of Nrf2 and NF-κB were assessed by western blotting, semi-quantitative RT-PCR, and luciferase reporter assays in RAW 264.7, an NF-κB reporter cell line, and HEK 293 transfected with an NF-κB reporter construct. RESULTS: Mice that were treated with a water extract of DS showed significant attenuation of lung inflammation induced by intranasal lipopolysaccharide (LPS) compared to control mice treated with vehicle. In vitro experiments show that DS activated Nrf2, an anti-oxidant transcription factor that protects from various inflammatory diseases, and induced Nrf2-regulated genes including GCLC, NQO-1 and HO-1. In addition, DS suppressed NF-κB activity and reduced the production of pro-inflammatory cytokines. Transfection experiment indicates that inhibition of NF-κB likely occurred upstream of IKK complex. Furthermore, DS enhanced the expression of HO-1 and suppressed that of IL-1ß and TNF-α in inflamed mouse lungs. CONCLUSIONS: These results suggest that the therapeutic effects of DS are related with suppression of inflammation, which is, at least in part, mediated by activation of anti-inflammatory factor Nrf2 and inhibition of pro-inflammatory factor NF-κB.

Vitamin C Up-regulates Expression of CD80, CD86 and MHC Class II on Dendritic Cell Line, DC-1 Via the Activation of p38 MAPK.

Vitamin C is an essential water-soluble nutrient which primarily exerts its effect on host defense mechanisms and immune homeostasis, but the mechanism related to immune-potentiation is poorly understood. Since dendritic cells (DCs) are known as a potent antigen presenting cell (APC) that could enhance the antigen specific immune responses, we investigate the effects of vitamin C on activation of DCs and its related mechanism by using dendritic cell lines, DC-1. First, we found that there was no damage on DC-1 by 2.5 mM of vitamin C. In the presence of vitamin C, the expression of CD80, CD86, and MHC molecules was increased, but it was decreased by the pre-treatment of SB203580, p38 MAPK-specific inhibitor. We confirmed the phosphorylation of p38 MAPK was increased by the treatment of vitamin C. Taken together, these results suggest that vitamin C could enhance the activity of dendritic cells via the up-regulation of the expression of CD80, CD86, and MHC molecules and the activation of p38 MAPK is related to this process.