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.
ABSTRACT 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.
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ABSTRACT: Praeruptorins belonging to the angular-type pyranocoumarins are bioactive constituents that have been isolated from some Peucedanum species such as P. praeruptorum, which is used in traditional Chinese medicine for treatment of cold, cough, upper respiratory infections, and so forth. Many reports have demonstrated that the beneficial pharmacological effects of P. praeruptorum root on cardiovascular, pulmonary, immune, and nervous system diseases were attributed to the presence of praeruptorins. The aim of this review is to explain the recent efforts of scientists in pharmacological screening of natural and synthetic praeruptorin derivatives, studying the mechanisms of some praeruptorins action, pharmacokinetics, toxicity, and relevant structure-activity relationships. Based on reported data about the pharmacological properties of praeruptorins and semisynthetic derivatives of them, it is hopeful that in the near future more studies focus on the discovery of the new application and therapeutic uses of these bioactive compounds and understanding the specific mechanisms of them. The present discusses the reports on molecular and biological activities of praeruptorins of the genus Peucedanum, from 1976 onwards.11/2013; 2013:343808. DOI:10.1155/2013/343808
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ABSTRACT: The genus Peucedanum (Apiaceae) comprising more than 120 species are widely distributed in Europe, Asia and Africa. The ethnopharmacologial history of this genus indicated that some extracts of aerial and underground parts of several Peucedanum species have used in folk medicine for treatment of various conditions, such as cough, cramps, pain, rheumatism, asthma and angina.Journal of Ethnopharmacology 09/2014; 156. DOI:10.1016/j.jep.2014.08.034 · 2.94 Impact Factor
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ABSTRACT: Klotho is a recently discovered antiaging protein. Although many researchers are investigating the roles of Klotho in chronic kidney diseases and cancer, however, there are no studies on the roles of Klotho in chronic pulmonary diseases. The purpose of this study was to define the role of Klotho in pulmonary fibrosis using a murine model of ovalbumin (OVA)-induced chronic asthma and in BEAS-2B human bronchial epithelial cells. In an in vivo experiment, mice were sensitized by intraperitoneal injection of OVA (20 μg/mouse), followed 1 week later by an airway challenge with 1 % OVA solution delivered three times a week for 4 weeks. In an in vitro experiment, we investigated the effects of stimulated with interleukin (IL)-4 and tumor necrosis factor (TNF)-α on Klotho protein and VEGF and transforming growth factor (TGF)-β1/Smad3 signaling in BEAS-2B cells. Klotho decreased and VEGF and TGF-β1 levels increased with increasing duration of OVA challenge. Similar findings were found for the expression of these proteins in lung tissue. The collagen content in lung tissue increased with repeated OVA challenge. In the in vitro experiment, Klotho expression decreased and VEGF and TGF-β1/Smad3 expression increased after IL-4 (50 ng/mL) and TNF-α (50 ng/mL) stimulation. Pretreatment with 25, 50, and 100 ng/mL of Klotho protein significantly attenuated the increases in VEGF and TGF-β1/Smad3 expression levels after IL-4 and TNF-α treatment, and reduced α-smooth muscle actin expression in concentration-dependent manner. Klotho protein inhibited the fibrotic response by suppressing VEGF and TGF-β1/Smad3 expression. These results suggest that Klotho protein may be crucial to inhibiting fibrosis associated with chronic airway diseases.Archive für Toxikologie 06/2014; DOI:10.1007/s00204-014-1282-y · 5.08 Impact Factor