Effect of Bufei Yishen Prescription on Airway Mucus Hypersecretion and Notch3 and HES1 Expression in Lung Tissues of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

ObjectiveTo observe the effects of Bufei Yishen prescription on airway mucus hypersecretion and Notch signaling pathway related protein Notch3 and enhancer of split homologue 1 （HES1） in rats with chronic obstructive pulmonary disease （COPD） and to explore its action mechanism. MethodForty-eight SD rats were randomly divided into the control group， model group， Bufei Yishen prescription group， and aminophylline （APL） group，with 12 rats in each group. The stable COPD rat model was established via cigarette smoking exposure combined with Klebsiella bacterial infection for 12 weeks， and the corresponding drugs （3.7 g·kg-1·d-1 Bufei Yishen prescription and 54 mg·kg-1·d-1 APL） were administered by gavage during the next eight weeks. After the last administration at week 20， the lung tissue was sampled for observing the pathological changes and the rat lung function was detected. The tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and mucoprotein 5AC （MUC5AC） in bronchial alveolar lavage fluid and the mRNA and protein expression levels of Notch3， HES1， and MUC5AC in lung tissues were assayed. ResultCompared with the control group， the model group exhibited significantly weakened pulmonary function （P<0.05，P<0.01）， reduced average number of alveoli （P<0.01）， elevated mean linear intercept （P<0.01）， and up-regulated TNF-α， IL-6， and MUC5AC in bronchial alveolar lavage fluid and Notch3， HES1， and MUC5AC mRNA and protein expression in lung tissue （P<0.05，P<0.01）. Compared with the model group， Bufei Yishen prescription and APL remarkably enhanced pulmonary function， alleviated its pathological injury （P<0.05，P<0.01）， and down-regulated TNF-α， IL-6， and MUC5AC in bronchial alveolar lavage fluid and the mRNA and protein expression levels of Notch3， HES1， and MUC5AC in lung tissues （P<0.05，P<0.01）. ConclusionThe mechanism of Bufei Yishen prescription in inhibiting airway mucus hypersecretion of COPD rats was related to its regulation of Notch3 and HES1.

Progress in application of genetically engineered mice exposed to cigarette smoke in research on drug targets and pathogenesis of COPD / 中国药理学通报

Chronic obstructive pulmonary disease (COPD) is a common illness of respiratory system, seriously threatening human life and health. Emergence and development of COPD are results of inter-actions between genes and pathogenic factors. The combination of cigarette smoking exposure and genetically engineered mice is able to make similar biological effects of special genes under pathogenic condition of cigarette smoke exposure. The article summarizes the method practice on study of drug targets, inflammation and immune in COPD, analyzes the results of these studies, and describes the basic process of the method, aiming to provide reference for research on pathogenesis and drugs of COPD.

Effective-constituent compatibility-based analysis of Bufei Yishen formula, a traditional herbal compound as an effective treatment for chronic obstructive pulmonary disease / 中西医结合学报

OBJECTIVE@#Critical effective constituents were identified from Bufei Yishen formula (BYF), a traditional herbal compound and combined as effective-constituent compatibility (ECC) of BYF I, which may have potential bioactive equivalence to BYF.@*METHODS@#The active constituents of BYF were identified using four cellular models and categorised into Groups 1 (Bufeiqi), 2 (Bushen), 3 (Huatan) and 4 (Huoxue) according to Chinese medicinal theory. An orthogonal design and a combination method were used to determine the optimal ratios of effective constituents in each group and the ratios of "Groups 1 to 4" according to their pharmacological activity. We also comprehensively assessed bioactive equivalence between the BYF and the ECC of BYF I in a rat model of chronic obstructive pulmonary disease (COPD).@*RESULTS@#We identified 12 active constituents in BYF. The numbers of constituents in Groups 1 to 4 were 3, 2, 5 and 2, respectively. We identified the optimal ratios of effective constituents within each group. In Group 1, total ginsenosides:Astragalus polysaccharide:astragaloside IV ratio was 9:5:2. In Group 2, icariin:schisandrin B ratio was 100:12.5. In Group 3, nobiletin:hesperidin:peimine:peiminine:kaempferol ratio was 4:30:6.25:0:0. In Group 4, paeoniflorin:paeonol ratio was 4:1. An orthogonal design was then used to establish the optimal ratios of Group 1, Group 2, Group 3 and Group 4 in ECC of BYF I. The ratio for total ginsenosides:Astragalus polysaccharide:astragaloside IV:icariin:schisandrin B:nobiletin:hesperidin:peimine:paeoniflorin:paeonol was determined to be 22.5:12.5:5:100:12.5:4:30:6.25:25:6.25. A comprehensive evaluation confirmed that ECC of BYF I presented with bioactive equivalence to the original BYF.@*CONCLUSION@#Based on the ECC of traditional Chinese medicine formula method, the effective constituents of BYF were identified and combined in a fixed ratio as ECC of BYF I that was as effective as BYF itself in treating rats with COPD.

Inhibitory effect of Panax notoginseng saponins on alveolar epithelial to mesenchymal transition / 中国中药杂志

In the study, the effects of Panax notoginseng saponins (PNS) on alveolar epithelial to mesenchymal transition (EMT) and extracellular matrix degradation were observed in a type of human alveolar epithelial cell, A549 cells, stimulated by TGF-beta1. Firstly, MTT method was applied to evaluation of cellular proliferation and found that PNS from 12.5 mg x L(-1) to 200 mg x L(-1) dosage could not inhibit significantly cellular proliferation. Then, cells were divided into five groups, normal group, TGF-beta1 group, TGF-beta1 + 50 mg x L(-1) PNS group, TGF-beta1 + 100 mg x L(-1) PNS group and TGF-beta1 + 200 mg x L(-1) PNS group. Normal cells were not stimulatec by TGF-beta1; TGF-beta1 cells were only stimulated by TGF-beta1 and the other cells were stimulated by TGF-beta1 with different doses of PNS, respectively. After stimulation, cells and supernatants were collected for assays. Cellular roundness was applied to quantitative evaluation of morphological change. Immunocytochemistry was applied to examine E-cadherion, a-SMA and FN proteins expression in the cells. Enzyme linked-immunosorbent assay was applied to MMP-9 and TIMP-1 levels. The results showed that EMT of A549 cells was induced by TGF-beta1, showing significant change of roundness, E-cadherion, alpha-SMA and FN (P < 0.05, P < 0.01). Compared to TGF-beta1, PNS significantly inhibited the changes of roundness (P < 0.05), FN and alpha-SMA (P < 0.05, P < 0.01) and not significantly inhibited the change of E-cadherion. Furthermore, MMP-9 levels were significantly increased by TGFbeta1 stimulation (P < 0.05), without significant change of TIMP-1. Compared with TGF-beta1, PNS could significantly increase MMP-9 level (P < 0.05) and decrease TIMP-1 levels (P < 0.05, P < 0.01). In conclusion, PNS could inhibit alveolar epithelial cell EMT induced by TGF-beta1, with increase of extracellular matrix degradation ability, which showed anti-fibrosis of lung ability.