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Searching for synergistic bronchodilators and novel therapeutic regimens for chronic lung diseases from a traditional Chinese medicine, Qingfei Xiaoyan Wan.

Hou Y, Cheng B, Zhou M, Fang R, Jiang M, Hou W, Bai G - PLoS ONE (2014)

Bottom Line: Classical Chinese pharmacopeias describe numerous excellent herbal formulations, and each prescription is an outstanding pool of effective compounds for drug discovery.Arctiin, arctigenin, descurainoside and descurainolide B, four lignin compounds that showed synergistic bronchodilation effects with ephedrine, were revealed.The synergistic mechanism of arctigenin with the β2ARagonist involved with the reduction of free Ca2+ was clarified by a dual-luciferase reporter assay for intracellular calcium and the Ca2+ indicator fluo-4/AM to monitor changes in the fluorescence.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.

ABSTRACT
Classical Chinese pharmacopeias describe numerous excellent herbal formulations, and each prescription is an outstanding pool of effective compounds for drug discovery. Clarifying the bioactivity of the combined mechanisms of the ingredients in complex traditional Chinese medicine formulas is challenging. A classical formula known as Qingfei Xiaoyan Wan, used clinically as a treatment for prevalent chronic lung disease, was investigated in this work. A mutually enhanced bioactivity-guided ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) characterization system was proposed, coupled with a dual-luciferase reporter assay for β2AR-agonist cofactor screening. Arctiin, arctigenin, descurainoside and descurainolide B, four lignin compounds that showed synergistic bronchodilation effects with ephedrine, were revealed. The synergistic mechanism of arctigenin with the β2ARagonist involved with the reduction of free Ca2+ was clarified by a dual-luciferase reporter assay for intracellular calcium and the Ca2+ indicator fluo-4/AM to monitor changes in the fluorescence. The relaxant and contractile responses of airway smooth muscle are regulated by crosstalk between the intracellular cAMP and calcium signaling pathways. Our data indicated the non-selective βAR agonist ephedrine as the principal bronchodilator of the formula, whereas the lignin ingredients served as adjuvant ingredients. A greater understanding of the mechanisms governing the control of these pathways, based on conventional wisdom, could lead to the identification of novel therapeutic targets or new agents for the treatment of asthma and COPD.

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The bronchodilator effect of QFXY on an atomized His-induced guinea pig asthma model (A) and the guinea pig tracheal muscle relaxant test (B).The values are presented as the mean ± SEM (n = 5). *P<0.05, **P<0.01, ***P<0.001, compared to the control group; #P<0.05, middle dose QFXY compared to the EE group.
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pone-0113104-g001: The bronchodilator effect of QFXY on an atomized His-induced guinea pig asthma model (A) and the guinea pig tracheal muscle relaxant test (B).The values are presented as the mean ± SEM (n = 5). *P<0.05, **P<0.01, ***P<0.001, compared to the control group; #P<0.05, middle dose QFXY compared to the EE group.

Mentions: The guinea pig asthma model was established to validate the bronchodilation effect of high, middle and low doses of QFXY (397.5, 132.5, and 44.1 mg/100 g, respectively) and EE (0.146 mg/100 g)which containing the same dose of ephedrine (about 21.9 µg) with the middle dose QFXY. As shown in Figure 1A, 10−6 mol/L salbutamol (Sal) used as a positive control prolonged the latent period by approximately 1.48-fold. QFXY inhibited asphyxial convulsions in a concentration- dependent manner. The increasing rates of the high, middle and low doses were approximately 1.76-, 1.07-, and 0.22-fold, respectively. The EE contained the identical dose of ephedrine as the middle dose of QFXY and prolonged the latent period only 0.46-fold. Additionally, the identical effect was observed on the guinea pig tracheal muscle relaxant test, and the EC50 of the middle QFXY dose was more effective than the EE extract (Figure 1B). Differing from Sal and the EE extract, the relaxant effect of QFXY was not completely inhibited by 10−7 mol/L Pro. As a result, QFXY was more effective for reducing the severity of bronchoconstriction after exposing His or Ach stimulation than when the ephedrine extract was used alone. In addition to the monarch drug (Herba Ephedrae), other ingredients played a role in the anti-asthmatic action.


Searching for synergistic bronchodilators and novel therapeutic regimens for chronic lung diseases from a traditional Chinese medicine, Qingfei Xiaoyan Wan.

Hou Y, Cheng B, Zhou M, Fang R, Jiang M, Hou W, Bai G - PLoS ONE (2014)

The bronchodilator effect of QFXY on an atomized His-induced guinea pig asthma model (A) and the guinea pig tracheal muscle relaxant test (B).The values are presented as the mean ± SEM (n = 5). *P<0.05, **P<0.01, ***P<0.001, compared to the control group; #P<0.05, middle dose QFXY compared to the EE group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232530&req=5

pone-0113104-g001: The bronchodilator effect of QFXY on an atomized His-induced guinea pig asthma model (A) and the guinea pig tracheal muscle relaxant test (B).The values are presented as the mean ± SEM (n = 5). *P<0.05, **P<0.01, ***P<0.001, compared to the control group; #P<0.05, middle dose QFXY compared to the EE group.
Mentions: The guinea pig asthma model was established to validate the bronchodilation effect of high, middle and low doses of QFXY (397.5, 132.5, and 44.1 mg/100 g, respectively) and EE (0.146 mg/100 g)which containing the same dose of ephedrine (about 21.9 µg) with the middle dose QFXY. As shown in Figure 1A, 10−6 mol/L salbutamol (Sal) used as a positive control prolonged the latent period by approximately 1.48-fold. QFXY inhibited asphyxial convulsions in a concentration- dependent manner. The increasing rates of the high, middle and low doses were approximately 1.76-, 1.07-, and 0.22-fold, respectively. The EE contained the identical dose of ephedrine as the middle dose of QFXY and prolonged the latent period only 0.46-fold. Additionally, the identical effect was observed on the guinea pig tracheal muscle relaxant test, and the EC50 of the middle QFXY dose was more effective than the EE extract (Figure 1B). Differing from Sal and the EE extract, the relaxant effect of QFXY was not completely inhibited by 10−7 mol/L Pro. As a result, QFXY was more effective for reducing the severity of bronchoconstriction after exposing His or Ach stimulation than when the ephedrine extract was used alone. In addition to the monarch drug (Herba Ephedrae), other ingredients played a role in the anti-asthmatic action.

Bottom Line: Classical Chinese pharmacopeias describe numerous excellent herbal formulations, and each prescription is an outstanding pool of effective compounds for drug discovery.Arctiin, arctigenin, descurainoside and descurainolide B, four lignin compounds that showed synergistic bronchodilation effects with ephedrine, were revealed.The synergistic mechanism of arctigenin with the β2ARagonist involved with the reduction of free Ca2+ was clarified by a dual-luciferase reporter assay for intracellular calcium and the Ca2+ indicator fluo-4/AM to monitor changes in the fluorescence.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.

ABSTRACT
Classical Chinese pharmacopeias describe numerous excellent herbal formulations, and each prescription is an outstanding pool of effective compounds for drug discovery. Clarifying the bioactivity of the combined mechanisms of the ingredients in complex traditional Chinese medicine formulas is challenging. A classical formula known as Qingfei Xiaoyan Wan, used clinically as a treatment for prevalent chronic lung disease, was investigated in this work. A mutually enhanced bioactivity-guided ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) characterization system was proposed, coupled with a dual-luciferase reporter assay for β2AR-agonist cofactor screening. Arctiin, arctigenin, descurainoside and descurainolide B, four lignin compounds that showed synergistic bronchodilation effects with ephedrine, were revealed. The synergistic mechanism of arctigenin with the β2ARagonist involved with the reduction of free Ca2+ was clarified by a dual-luciferase reporter assay for intracellular calcium and the Ca2+ indicator fluo-4/AM to monitor changes in the fluorescence. The relaxant and contractile responses of airway smooth muscle are regulated by crosstalk between the intracellular cAMP and calcium signaling pathways. Our data indicated the non-selective βAR agonist ephedrine as the principal bronchodilator of the formula, whereas the lignin ingredients served as adjuvant ingredients. A greater understanding of the mechanisms governing the control of these pathways, based on conventional wisdom, could lead to the identification of novel therapeutic targets or new agents for the treatment of asthma and COPD.

Show MeSH
Related in: MedlinePlus