Searching for synergistic bronchodilators and novel therapeutic regimens for chronic lung diseases from a traditional Chinese medicine, Qingfei Xiaoyan Wan.
Searching for synergistic bronchodilators and novel therapeutic regimens for chronic lung diseases from a traditional Chinese medicine, Qingfei Xiaoyan Wan.
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从中药中寻找慢性肺部疾病的协同支气管扩张剂和新的治疗方案，清肺消炎丸
DOI：
10.1371/journal.pone.0113104
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Bai G
中科院分区：
文献类型：
--
作者：
Hou Y;Cheng B;Zhou M;Fang R;Jiang M;Hou W;Bai G
中国古典药典描述了许多优秀的草药配方，每个处方都是药物发现的有效化合物的杰出池。阐明复杂中药配方中成分的组合机制的生物活性具有挑战性。本课题研究了临床上治疗慢性肺病的经典方剂清肺消炎丸。提出了一种相互增强的生物活性导向的超高效液相色谱/四极杆飞行时间质谱（UPLC/Q-TOF-MS）表征系统，并结合双荧光素酶报告基因分析用于β 2 AR激动剂辅因子的筛选。牛蒡苷、牛蒡苷元、莴苣苷和莴苣苷B是4种与麻黄碱具有协同支气管扩张作用的木质素类化合物。牛蒡子苷元与β 2AR激动剂协同作用的机制与胞内钙离子的减少有关，通过双荧光素酶报告细胞内钙离子和钙离子指示剂fluo-4/AM监测荧光的变化来阐明。气道平滑肌的舒张和收缩反应受细胞内cAMP和钙信号通路之间的串扰调节。我们的数据表明，非选择性βAR激动剂麻黄碱是该配方的主要支气管扩张剂，而木质素成分作为辅助成分。基于传统知识，更好地了解这些途径的控制机制，可能会导致识别用于治疗哮喘和COPD的新治疗靶点或新药物。
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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DOI：
10.1186/1476-9255-8-16
发表时间：
2011-07-07
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
Lee S;Shin S;Kim H;Han S;Kim K;Kwon J;Kwak JH;Lee CK;Ha NJ;Yim D;Kim K
通讯作者：
Kim K
DOI：
10.1155/2011/382789
发表时间：
2011
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Holzinger F;Chenot JF
通讯作者：
Chenot JF
影响因子：
24.3
作者：
Hall, IP
通讯作者：
Hall, IP
影响因子：
3.9
作者：
Hong, Feng;Haldeman, Brian D.;Jackson, Del;Carter, Mike;Baker, Jonathan E.;Cremo, Christine R.
通讯作者：
Cremo, Christine R.
影响因子：
4.3
作者：
Cheng, Binfeng;Hou, Yuanyuan;Bai, Gang
通讯作者：
Bai, Gang