Jin-Ah Lee

Anti-asthmatic effects of Angelica dahurica against ovalbumin-induced airway inflammation via upregulation of heme oxygenase-1

Asthma is a chronic immune inflammatory disease characterized by variable airflow obstruction. The present study was undertaken to assess the effects of an Angelica dahurica Bentham et Hooker ethanolic extract (AD) on airway inflammation in an ovalbumin (OVA)-induced airway inflammation model. Mice that received AD displayed significantly lower airway eosinophilia, cytokine levels, including interleukin (IL)-4, IL-5, and tumor necrosis factor (TNF)-alpha levels, mucus production and immunoglobulin (Ig)E, compared with OVA-induced mice. In our experiments, AD treatment reduced airway inflammation and suppressed oxidative stress in the OVA-induced asthma model, partly via induction of heme oxygenase (HO)-1. The effects of AD on OVA-induced HO-1 induction were partially reversed by the HO-1 inhibitor, tin protoporphyrin (SnPP). Our results clearly indicate that AD is a suppressor of airway allergic inflammation, and may thus be effectively used as an anti-inflammatory drug in the treatment of asthma.

Anti-inflammatory activity of Angelica dahurica ethanolic extract on RAW264.7 cells via upregulation of heme oxygenase-1

In this study, we analyzed the anti-inflammatory effects of Angelica dahurica Bentham et Hooker ethanolic extract (ADEE) on RAW264.7 cells, to understand the mechanism underlying its observed effects. ADEE inhibited cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, leading to the suppression of COX-2-derived prostaglandin E(2) and iNOS-derived production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. These inhibitory effects of ADEE were accompanied by the reduced production of tumor necrosis factor α and interleukin (IL)-6. ADEE also inhibited nuclear factor κB (NFκB) translocation to the nucleus by interrupting inhibitor kappa Bα (IκBα) degradation. ADEE upregulated heme oxygenase 1 expression, and treatment with tin protoporphyrin IX (SnPP), a selective inhibitor of HO-1, reversed the LPS-induced generation of proinflammatory cytokines. ADEE also induced IL-4 and IL-5 expression in concanavalin-A-stimulated splenocytes. These results suggest that ADEE has anti-inflammatory activity, which acts via the suppression of the NF-κB pathway.

Hepatoprotective and Antioxidative Activities of Cornus officinalis against Acetaminophen-Induced Hepatotoxicity in Mice

The fruit of Cornus officinalis Sieb. et Zucc. is commonly prescribed in Asian countries as a tonic formula. In this study, the hepatoprotective effect of ethanolic extracts of the fruit of C. officinalis (ECO) was investigated in a mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice with ECO (100, 250, and 500 mg/kg for 7 days) significantly prevented the APAP (200 mg/kg) induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, and LDH). Parallel to these changes, ECO treatment also prevented APAP-induced oxidative stress in the mice liver by inhibiting lipid peroxidation (MDA) and restoring the levels of antioxidant enzymes (SOD, CAT, and HO-1) and glutathione. Liver injury and collagen accumulation were assessed using histological studies by hematoxylin and eosin staining. Our results indicate that ECO can prevent hepatic injuries associated with APAP-induced hepatotoxicity by preventing or alleviating oxidative stress.

Anti-inflammatory Effects of Amomum compactum on RAW 264.7 Cells via Induction of Heme Oxygenase-1

Amomum compactum is commonly used in Korean traditional medicine. In this study, we demonstrate that A. compactum ethanolic extract (ACEE) has anti-inflammatory effects in a lipopolysaccharide-induced RAW 264.7 cell model of inflammation. In this system, ACEE prominently inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and inhibited the protein expression of inducible nitric oxide synthase and cyclooxygenase-2. Furthermore, ACEE treatment inhibited the translocation of nuclear factor-kappaB (NF-κB) and the degradation of inhibitory factor-kappaB alpha, but enhanced the expression of heme oxygenase (HO)-1 and the nuclear translocation of nuclear factor-erythroid 2 (Nrf2). Treatment with tin protoporphyrin IX dichloride (SnPP), a selective HO-1 inhibitor, reversed the ACEE-induced suppression of NO production, suggesting that the induction of HO-1 is involved in the suppression of NO, TNF-α, and IL-6 production by ACEE. Taken together, these results suggest that ACEE have anti-inflammatory effects occurring through HO-1 induction, which leads to suppression of the blocking NF-κB.

Alpinia katsumadai H AYATA Seed Extract Inhibit LPS-Induced Inflammation by Induction of Heme Oxygenase-1 in RAW264.7 Cells

In the present study, we investigated the effects of Alpinia katsumadai HAYATA (Zingiberaceae) seed ethanolic extract (AKEE) and its three components on the production of inflammatory mediators and some potential underlying mechanisms in lipopolysaccharide (LPS)-induced inflammation RAW264.7 cells. The whole formula, AKEE, and three major component compounds were then evaluated for their effects on inflammation-related parameters using LPS-induced RAW264.7 cells. Production of namely nitric oxide (NO) and cytokine levels were measured by the Griess reagent and ELISA, respectively. To investigate the underlying mechanisms of anti-inflammatory activities of AKEE, protein expression of nitric oxide synthase (inducible nitric oxide synthase, iNOS), heme oxygenase-1 (HO-1), and nuclear factor-kappa B (NF-κB) were evaluated by western blot analysis. AKEE and the major group of compounds in AKEE (alpinetin, cardamonin, and pinocembrin) complement exert anti-inflammatory effects for NO and PGE2 production. In addition, AKEE treatment significantly inhibited the LPS-induced production of interleukin-6 and tumor necrosis factor (TNF)-α, as well as the expression of iNOS. AKEE also induced HO-1 expression in RAW264.7 cells and inhibited the nuclear translocation of NF-κB by preventing degradation of the inhibitor kappa B-alpha. We also demonstrated that the effects of AKEE on TNF-α production were partially reversed by the HO-1 inhibitor tin protoporphyrin. These results indicate that AKEE and its major component may have anti-inflammatory activity via induction of HO-1 expression was partly responsible for the anti-inflammatory effects.

Anti-asthmatic effect of schizandrin on OVA-induced airway inflammation in a murine asthma model.

Asthma comprises a triad of reversible airway obstruction, bronchial smooth muscle cell hyperreactivity to bronchoconstrictors, and chronic bronchial inflammation. Clinical and experimental findings have established eosinophilia as a sign of allergic disorders. In the present investigation, we evaluated the anti-asthmatic effects of schizandrin and its underlying mechanisms in an in vivo murine asthmatic model. To accomplish this, female BALB/c mice were sensitized and challenged with ovalbumin (OVA), and examined for the following typical asthmatic reactions: increased numbers of eosinophils and other inflammatory cells in bronchoalveolar lavage fluid (BALF); production of Th1 cytokines (such as tumor necrosis factor (TNF)-α in BALF); production of Th2 cytokines (such as interleukin IL-4 and IL-5) in BALF; presence of total and OVA-specific immunoglobulins (Ig)E in serum; presence of oxidative stress; hyperplasia of goblet cells in the lung; and marked influx of inflammatory cells into the lung. Our results collectively show that schizandrin exerts profound inhibitory effects on accumulation of eosinophils into the airways and reduces the levels of IL-4, IL-5, IFN-γ, and TNF-α in BALF. Additionally, schizandrin suppresses the production of reactive oxygen species (ROS) in a dose-dependent manner, and inhibits goblet cell hyperplasia and inflammatory cell infiltration in lung tissue. Thus, schizandrin has anti-asthmatic effects, which seem to be partially mediated by reduction of oxidative stress and airway inflammation, in a murine allergic asthma model. These results indicate that schizandrin may be an effective novel therapeutic agent for the treatment of allergic asthma.

Protective effects of allantoin against ovalbumin (OVA)-induced lung inflammation in a murine model of asthma

Asthma is characterized by difficulty in breathing because of the constriction of the smooth muscles of the bronchi, as a result of inflammation. In the present study, we focus on the protective effects of allantoin against ovalbumin (OVA)-induced lung inflammation in a murine allergic model, and assess cytokine release, eosinophilia, and mucus hypersecretion. Allantoin treatment led to significant reduction in the levels of Ig(immunoglobulin)E and T-helper-2-type cytokines, such as IL(interleukin)-4 and IL-5, in bronchoalveolar lavage (BAL) fluid. Airway inflammatory-cell infiltration was remarkably alleviated in allantoin-treated asthma groups, compared with the control group. Moreover, allantoin-treated asthma groups exhibited a marked decrease in cytokine mRNA expression in lung tissues, compared with the control group. The effectiveness of allantoin was similar to that of montelukast, used as a positive control. These results support the utility of allantoin as a protective agent against asthma.

Alpinia katsumadai seed extract attenuate oxidative stress and asthmatic activity in a mouse model of allergic asthma

Allergic asthma is a chronic inflammatory disorder of the airways characterized by biphasic airway obstruction. Oxidative stress plays an important role in the development of asthmatic conditions. Thus, identification of oxidative stress markers in bronchoalveolar lavage fluid (BALF) and lung tissue from ovalbumin (OVA)-sensitized mice could provide new insights into both the pathogenesis of the disease and the possible use of anti-oxidants to alleviate disease severity. In this study, we investigated the effect of an ethanolic extract of Alpinia katsumadai seeds (AK) on a murine model of OVA-induced asthma model. The anti-oxidant and anti-asthmatic effects of AK on OVA-induced murine airway reaction were determined through observation of Th2-type cytokine levels, eosinophil recruitment, and lung histopathology. AK was found to significantly inhibit increases in Th2-type cytokines and mRNA expression such as IL-4 and IL-5 in BALF and lung tissue, and effectively suppressed IgE, IgG2a, eosinophilia, and mucus hypersecretion in the asthmatic mouse model. Also, the generation of reactive oxygen species (ROS) in BALF was diminished by AK treatment. These findings indicate that oxidative stress may play a crucial role in the pathogenesis of OVA-induced asthma model and that AK may have applications in the treatment of asthma.

Protective Effects of Mentha haplocalyx Ethanol Extract (MH) in a Mouse Model of Allergic Asthma

Mentha haplocalyx Briq., a commonly used herb in traditional Oriental medicine, has a variety of known pharmacological properties. However, neither the protective effects of Mentha haplocalyx ethanol extract (MH) against inflammation of the airway in an asthmatic model nor the mechanisms involved, have previously been reported. In the present study, an ovalbumin (OVA)‐induced mouse model of allergic asthma was used to investigate whether MH was effective against the disease through regulation of airway inflammation. The MH treatment significantly inhibited increases in immunoglobulin (Ig) E and T‐helper 2 (Th2)‐type cytokines such as IL‐4 and IL‐5 in bronchoalveolar lavage fluid (BALF) and lung tissue. Inflammatory cell infiltration of the airway in mice treated with MH was effectively alleviated when compared with infiltration seen in the OVA‐induced group. These data indicated that decreased cytokine levels are the result of the decreased number of invaded leukocytes. Also, the generation of reactive oxygen species (ROS) in BALF was diminished by MH treatment. Taken together, these findings indicate that the administration of MH may have potential therapeutic value in the treatment of inflammatory disease. Copyright

Protective effects of Ulmus davidiana var. japonica against OVA-induced murine asthma model via upregulation of heme oxygenase-1

AIM OF THE STUDY Traditionally, the stem and root bark of Ulmus davidiana var. japonica (Ulmaceae) are Korean herbal medicines used for anti-inflammatory and anticancer therapy. In this study, we investigated the protective effects of Ulmus davidiana var. japonica ethanolic extract (UD) in a murine asthma model. Furthermore, we determined whether heme oxygenase (HO)-1 is required for the protective activity of UD. MATERIALS AND METHODS Airways of ovalbumin (OVA)-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. UD was applied 1h prior to OVA challenge. Mice were administered UD orally at doses of 100 and 200mg/kg once daily on days 18-23. Bronchoalveolar lavage fluid (BALF) was collected 48 h after the final OVA challenge. Levels of interleukin (IL)-4 and IL-5 in BALF were measured using enzyme-linked immunosorbent assays (ELISAs). Lung tissue sections 4 microm in thickness were stained with Mayers hematoxylin and eosin for assessment of cell infiltration and mucus production with PAS (periodic acid shift reagent) staining, in conjunction with ELISA, immunohistochemistry and Western blot analyses for HO-1 protein expression. RESULTS AND CONCLUSION Orally administered UD significantly inhibited the number of OVA-induced inflammatory cells and IgE production, along with reduced T-helper (Th)2 cytokine levels, such as IL-4 and IL-5, in BALF and lung tissue. In addition, UD induced a marked decrease in OVA-induced reactive oxygen species (ROS), inflammatory cell infiltration and mucus production in lung tissue. These effects were correlated with HO-1 mRNA and protein induction. Our results indicate that UD protects against OVA-induced airway inflammation, at least in part, via HO-1 upregulation.