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

Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China.
Journal of ethnopharmacology (Impact Factor: 3). 02/2012; 141(1):314-21. DOI: 10.1016/j.jep.2012.02.037
Source: PubMed


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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    • "In 2012, Xiong and coworkers [48] confirmed the inhibitory effect of CPPD, containing praeruptorins, on allergic airway inflammation and T helper cell type two predominant responses in a mouse model. Pd-la has shown potent anti-inflammatory effect in a murine model of chronic 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.
    Full-text · Article · Nov 2013
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    • "Peucedani Radix (Qian-hu in Chinese), the dried roots of Peucedanum praeruptorum Dunn (Apiaceae) [1], has been widely employed for the treatment of cough with thick sputum and dyspnoea , nonproductive cough and upper respiratory infections [2] for centuries in China. On modern pharmacological models, this herbal drug was highly marked for tracheal and pulmonary arteries relaxant [3], coronary dilatory [2], myocardial protective [4], antitumor-promoting [5] and anti-inflammatory [6] activities, etc. There are several classes of compounds reported in Peucedani Radix, and the major constituents are angular-type pyranocoumarins (APs) that are widely believed to make the main contribution to the pharmacological properties of Qian-hu [7]. "
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    ABSTRACT: As a widely used traditional herbal medicine, it is crucial to characterize the holistic metabolic profile of Peucedani Radix (Chinese name: Qian-hu). However, it is quite arduous to obtain the whole picture of chemical constituents appropriately with the existing analytical techniques that were based on HPLC-UV or LC-MS/MS system. In present investigation, nuclear magnetic resonance (NMR) spectroscopy coupled with principal components analysis (PCA) was introduced to metabolomic characterization of Qian-hu crude extracts without any chromatographic separation. In addition, the contents of praeruptorin A (PA) and proaeruptorin B (PB) in Qian-hu were simultaneously determined using quantitative (1)H NMR (q(1)H NMR) spectroscopy. Eighteen reference compounds (1-18), which were purified from this herbal drug extract previously, were recruited for the assignment of the protonic signals in the (1)H NMR spectra. Following PCA, 15 batches of Peucedani Radix were divided into two groups (I and II), and angular-type pyranocoumarins, in particular PA and PB, as well as 5-methoxycoumarin were demonstrated as the predominant markers being responsible for the distinguishment of Qian-hu from different districts. The contents of the two analytes (PA & PB) were calculated by the relative ratio of the integral values of the target peak for each compound to the known amount of the internal standard, formononetin (IS). The lower limits of quantitation were determined as 19.5μg/mL for both PA and PB. The quantitative results indicated that the contents of PA and PB showed quite variable qualities among different extract samples. Above all, (1)H NMR spectroscopy, that could not only provide comprehensive profiles of the metabolites but also achieve convenient determination of praeruptorin A and praeruptorin B, is a promising means for evaluating the medicinal samples of Peucedani Radix.
    Full-text · Article · Aug 2013 · Journal of pharmaceutical and biomedical analysis
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    ABSTRACT: A strategy of ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) coupled to recycling preparative HPLC was utilized to sensitively detect the minor constituents and preparatively isolate coumarin isomers from the petroleum ether extract of Peucedanum praeruptorum roots. UPLC-Q-TOF-MS was achieved on an Agilent ZORBAX Extend C-18 analytical column (50 mm × 2.1 mm i.d. 1.8 μm) using methanol:H2O as the mobile phase, and three pairs of coumarin isomers with similar polarity were detected. Then recycling preparative HPLC was successfully used in one step for the isolation and purification of these six compounds with optimized mobile phases (methanol: H2O, 73:27, 81:19, 78:22, v/v). The structures of six coumarins including three new coumarins named praeruptorin (F–H) (1, 3 and 6) were identified by spectroscopic analysis.
    No preview · Article · Feb 2012 · Chromatographia
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