Peucedanum japonicum extract attenuates allergic airway inflammation by inhibiting Th2 cell activation and production of pro-inflammatory mediators.

The root of Peucedanum japonicum Thunberg is traditionally used to treat coughs, colds, headache and inflammatory diseases in Korea and Japan. Its effects on allergic lung inflammation have not been investigated. To investigate the anti-asthmatic effects of Peucedanum japonicum extract (PJE) using a murine model of asthma and a lipopolysaccharide (LPS)-stimulated macrophage cell line. Mice underwent two rounds of sensitization with ovalbumin 1 week apart followed by four intranasal ovalbumin challenges on days 13-16. The control group received saline only. Two ovalbumin-sensitized groups were orally administered vehicle or PJE (200mg/kg) 5 days a week starting 1 week before the first ovalbumin sensitization. The third group was orally administered the asthma medication Montelukast (10mg/kg) on days 12-16. All animals were sacrificed on day 17. The lungs were assessed for histological features, inflammatory cell infiltration, Th2 cell activation and GATA-binding protein-3 (GATA-3) expression. The bronchoalveolar lavage fluid (BALF) was assessed for type 2 cytokine levels. The effect of PJE on the in vitro Th2 polarization of naïve CD4+ splenocytes and the production of pro-inflammatory mediators and cytokines by LPS-stimulated RAW 264.7 cells was evaluated. PJE treatment inhibited OVA-induced inflammatory cell infiltration, eosinophilia, Th2 activation, and GATA-3 expression in the lung, reduced the interleukin (IL)-5 and IL-13 levels in BALF, down-regulated Th2 activation in vitro, and inhibited the macrophage production of inducible nitric oxide, cyclooxygenase-2, tumor necrosis factor-α, and IL-6. PJE attenuated allergic airway inflammation by inhibiting Th2 cell activation and macrophage production of inflammatory mediators. Peucedanum japonicum may be candidate therapy for allergic lung inflammation.

Chun JM ，Lee AR ，Kim HS ，Lee AY ，Gu GJ ，Moon BC ，Kwon BI ... -  《-》

Reduced allergic lung inflammation by root extracts from two species of Peucedanum through inhibition of Th2 cell activation.

Peucedani Radix (PR), the root of Peucedanum praeruptorum Dunn (PPD) or Peucedanum decursivum (Miq.) Maxim. (PDM), has long been used in Korea to eliminate sputum, relieve cough, and reduce bronchus contraction. Furthermore, these therapeutic strategies are recognized as general and effective methods in western medicine as well as traditional Korean medicine. To determine and compare the anti-inflammatory effects of PPD extracts (PPDE) and PDM extracts (PDME) on allergic lung inflammation, using in vivo OVA-induced airway inflammation in mice and in vitro primary cell culture systems. Eight-week-old female C57BL/6 mice were placed into four groups (n=4 per group): saline control, OVA-induced allergic lung inflammation with vehicle, or PPDE (200mg/kg) or PDME (200mg/kg) treatment. PR extracts (PRE) were administered from 1 week before 1st OVA sensitization to the day before sacrifice. Mice were sacrificed 18h after last OVA intra-nasal challenge followed by histological and biochemical analyses. Inflammatory phenotypes were alleviated with oral administration of PRE. PRE treatment decreased mucus production in airway epithelium, inflammatory cell number, eosinophilia, type 2 cytokines, and histamine in bronchoalveolar lavage fluid (BALF). Mice with PRE administration showed diminished activated CD4 T cell (CD4+CD25+ cell) and GATA-3 level in the lung. In addition, PRE treatment reduced Th2 cell activation in vitro, using Th2 polarization system. Our findings indicate that the anti-inflammatory effects of PRE arise from reduced Th2 cell activation and validate the clinical use of PR in traditional Korean medicine.

Lee AR ，Chun JM ，Lee AY ，Kim HS ，Gu GJ ，Kwon BI ... -  《-》

Anthriscus sylvestris root extract reduces allergic lung inflammation by regulating interferon regulatory factor 4-mediated Th2 cell activation.

Anthriscus sylvestris L. Hoffmann (AS) is a perennial plant that grows in Asia and Eastern Europe. Its dried root is used to treat conditions such as asthma, bronchitis, and cough. The present study investigated the anti-inflammatory effects of whole AS extract (ASE) on allergic lung inflammation in vitro and in vivo as well as the underlying mechanisms. We used an ovalbumin (OVA)-induced asthma mouse model and in vitro primary T helper (Th)2 polarization system. Five groups of 8-week-old female C57BL/6 mice were divided into the following groups: saline control, or OVA-induced allergic asthma with vehicle, ASE (100 or 200 mg/kg), or dexamethasone (5 mg/kg) treatment for 7 days. ASE attenuated mucus secretion in airway epithelial cells, inflammatory cell infiltration, eosinophilia, and Th2 cytokine levels in bronchoalveolar lavage fluid. Mice administered ASE showed reductions in the activated cluster of differentiation 4+ T cell population and GATA-binding protein-3 gene expression in the lung, and diminished Th2 cell differentiation and activation in vitro. Furthermore, ASE-treated mice showed decreased interleukin-6 and interferon regulatory factor (IRF)4 expression, with corresponding reductions in nitric oxide levels in the lungs of asthmatic mice and in stimulated RAW cells. ASE exerts anti-asthmatic effects by inhibiting IRF4 expression and thereby suppressing Th2 cell activation.

Kim SB ，Lee AY ，Chun JM ，Lee AR ，Kim HS ，Seo YS ，Moon BC ，Kwon BI ... -  《-》

18β-Glycyrrhetinic acid, the major bioactive component of Glycyrrhizae Radix, attenuates airway inflammation by modulating Th2 cytokines, GATA-3, STAT6, and Foxp3 transcription factors in an asthmatic mouse model.

18β-Glycyrrhetinic acid (18Gly), the major bioactive component of Glycyrrhizae Radix, possesses anti-ulcerative, anti-inflammatory, and other pharmacological properties. Although 18Gly is associated with immunoregulatory functions of allergic diseases, the pathophysiological mechanisms of 18Gly action in allergic inflammatory lung disease have not been examined. Moreover, there are no in vivo studies on the anti-asthmatic effects of 18Gly in allergic asthma. We investigated its effect and mechanism of action in airway inflammation in a BALB/c mouse model of allergic asthma. Interestingly, 18Gly strongly suppressed airway hyperresponsiveness, accumulation of inflammatory cells, and levels of T helper type 2 (Th2) cytokines (interleukin (IL)-5 and IL-13) in bronchoalveolar lavage fluid (BALF). It also attenuated lung IL-5, IL-13, and IL-4 expression, but it upregulated peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression in lungs. Moreover, it exerted immunomodulatory effects by suppressing Th2 cytokines (IL-5, IL-13) production through upregulation of forkhead box p3 (Foxp3), and downregulation of signal transducer and activator of transcription (STAT6), GATA-binding protein 3 (GATA-3), and retinoic acid-related orphan receptor γ t (RORγt) expression. These results suggest that the anti-asthmatic activity of 18Gly may occur by the suppression of IL-5, IL-13, and OVA-specific Immunoglobulin E (IgE) production through inhibition of the RORγt, STAT6, GATA-3 pathways and upregulation of the Foxp3 transcription pathway. Also, 18Gly treatment was protective against the oxidative stress by inducing significant decrease of reactive oxygen species (ROS) generation in MH-S alveolar macrophage cells. Our results suggest that 18Gly can improve allergic asthma and can be a novel therapeutic component for the treatment of allergic asthma.

Kim SH ，Hong JH ，Lee JE ，Lee YC ... -  《-》

Attenuation of airway hyperreactivity and T helper cell type 2 responses by coumarins from Peucedanum praeruptorum Dunn in a murine model of allergic airway inflammation.

The root of Peucedanum praeruptorum Dunn (PPD) is a commonly used traditional Chinese medicine for the treatment of asthma. Its major constituents, coumarins, were presumed to be responsible for its efficacy. The potential of coumarins from PPD (CPPD) as anti-asthma agent was investigated. Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce allergic airway inflammation. CPPD was administered intragastrically before every OVA challenge. Airway reactivity to the intravenous administration of acetylcholine chloride was measured 48h after final OVA inhalation. Airway inflammation was evaluated by leukocyte counts of bronchoalveolar lavage fluid (BALF) and histopathological analysis of lung lesions. Levels of interleukin (IL)-4, IL-5, IL-10, IL-13 and IFN-γ in BALF and OVA-specific immunoglobulin (Ig) E in serum, and activity of eosinophil peroxidase (EPO) in lung was measured. The percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells among CD4(+) T cells in spleen was analyzed by flow cytometry. Compared with model group, CPPD significantly reduced airway hyperreactivity and airway eosinophilic inflammation, improved pathologic lesion of the lungs, reduced levels of IL-4, IL-5, IL-13 in BALF and OVA-specific IgE in serum, inhibited the activities of EPO in lung, and up-regulated levels of IL-10 and IFN-γ in BALF as well as the percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells in spleen. CPPD can significantly suppress OVA-induced airway inflammation, airway hyperreactivity and Th2 predominant response in mice, showing great therapeutic potential for the treatment of allergic asthma.

Xiong YY ，Wu FH ，Wang JS ，Li J ，Kong LY ... -  《-》