Yangqing Chenfei formula alleviates crystalline silica induced pulmonary inflammation and fibrosis by suppressing macrophage polarization.

OBJECTIVE: To explore the underlying mechanisms of the effects of Yangqing Chenfei formula (, YCF) on inflammation and fibrosis in silicosis via inhibition of macrophage polarization. METHODS: A silicotic rat model was established via a single intratracheal instillation of silica particles on the first day of week 0. Subsequently, YCF was administered intragastrically to silicotic rats during weeks 0-2 and 5-8 twice daily. The mouse-derived alveolar macrophage cell line was used to investigate the mechanisms of YCF in M1/M2 polarization. RESULTS: YCF treatment effectively inhibited lung pathological changes, including inflammatory cell infiltration and tissue damage, and increased the forced expiratory volume in the first 0.3 s, functional residual capacity, and maximal mid-expiratory flow in weeks 2 and 8. Furthermore, the treatment improved lung functions by upregulating tidal volume, pause increase, and expiratory flow at 50% tidal volume from weeks 5 to 8. Moreover, YCF could significantly suppressed the progression of inflammation and fibrosis, by reducing the levels of inflammatory cytokines, as well as collagen- I and III. YCF treatment also decreased the numbers of macrophages and M1/M2 macrophages and the level of transforming growth factor-ß (TGF-ß). Additionally, YCF5, the effective substance in YCF, decreased lipopolysaccharide and interferon-γ-induced M1 macrophage polarization in a concentration-dependent manner. The mechanism of anti-M1 polarization might be related to a decrease in extracellular signal-regulated kinase, c-JUN N-terminal kinase, P38, and P65 phosphorylation. Furthermore, YCF5 inhibited interleukin-4-induced M2 macrophages by decreasing the protein and mRNA expressions of arginase-1 and CD206 as well as the levels of profibrotic factors, such as TGF-ß and connective tissue growth factor. The mechanisms underlying the anti-M2 polarization of YCF5 were primarily associated with the inhibition of the nuclear translocation of phosphorylated signal transducer and activator of transcription 6 (p-STAT6). CONCLUSION: YCF significantly inhibits inflammation and fibrosis in silicotic rats probably via the suppression of M1/M2 macrophage polarization mediated by the inhibition of mitogen-activated protein kinase and nuclear factor kappa B signaling pathways and Janus kinase/STAT6 pathways.

Compatibility characteristics of Bufei Yishen formula Ⅲ in regulating chronic obstructive pulmonary disease mucus hypersecretion / 中华危重病急救医学

Objective:To evaluate the compatibility laws of effective-component compatibility of Bufei Yishen formula Ⅲ (ECC-BYFⅢ) in regulating mucus hypersecretion of chronic obstructive pulmonary disease (COPD).Methods:According to the efficacy of the original Chinese medicine, the components of ECC-BYFⅢ were divided into four categories: Buqi (Ginsenoside Rh1+Astragaloside), Bushen (Icariin), Huatan (Nobiletin), and Huoxue (Paeonol). The four categories were divided into 14 groups based on the method of mathematical permutation. ① The rats were divided into control group, model group, ECC-BYFⅢ, and different components compatibility groups according to the random number table, totaling 17 groups. COPD rat model in stable phase was established by cigarette smoke exposure combined with repeated bacterial infections. The corresponding drugs were given by gavage at the 9th week of modeling, and the samples were collected at the end of the 16th week. The levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase 1 (TIMP-1) in serum and bronchoalveolar lavage fluid (BALF), and the levels of mucin (MUC) 5AC in lung tissue and BALF were detected by enzyme linked immunosorbent assay (ELISA). ② Human lung epithelial cells BEAS-2B were divided into blank group, model group, and different components compatibility groups. Hypoxia-induced mucus hypersecretion model of human lung epithelial cells BEAS-2B was established 4 hours after corresponding drug pretreatment. The mRNA expressions of MUC5AC, MUC5B, and MUC1 were detected by quantitative polymerase chain reaction (PCR). The mucus secretion indexes of rats and BEAS-2B cells were evaluated by Region (R) value comprehensive evaluation method.Results:① Compared with the control group, MMP-9 in serum and BALF from the model group were significantly increased, the level of TIMP-1 was significantly decreased, and MUC5AC in lung tissue and BALF were significantly increased. The results of R value comprehensive evaluation showed that except for the Buqi and Bushen groups, ECC-BYFⅢ and other components compatibility groups significantly corrected mucus hypersecretion in COPD rats, ECC-BYFⅢ, Bushen Quxie, Fuzheng Huatan, and Quxie groups were much better (R values were 2.15±0.42, 2.11±0.23, 2.16±0.23 and 2.16±0.55, respectively), compared with the model group (R value: 3.00±0.00), the differences were statistically significant (all P < 0.05). ② Compared with the blank group, the mRNA expressions of MUC5AC, MUC5B, and MUC1 increased in the model group. But different components compatibility groups had no significant effects on the mucus secretion of BEAS-2B cells. ③ The comprehensive evaluation results of R value about each in vivo and in vitro index showed that ECC-BYFⅢ, Huoxue, Quxie, Bushen Huoxue, Fuzheng Huatan, Buqi Quxie groups significantly corrected the mucus hypersecretion (R values were 2.30±0.43, 2.33±0.44, 2.12±0.68, 2.27±0.64, 2.24±0.27 and 2.29±0.47, respectively), compared with the model group (R value: 3.00±0.00), the difference was statistically significant (all P < 0.01). The order was: Quxie > Fuzheng Huatan > Bushen Huoxue > Buqi Quxie > ECC-BYFⅢ > Huoxue. Conclusions:Different components compatibility of ECC-BYFⅢ had different effects on COPD mucus secretion. The components containing Huatan (Nobiletin) or Huoxue (Paeonol) showed a better inhibitory effect on mucus secretion.

Effects of therapies for regulating and reinforcing lung and kidney on osteoporosis in rats with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the efficacy and long-term effects of the three therapies for regulating and reinforcing lung and kidney (reinforcing lung and invigorating spleen, reinforcing lung and replenishing kidney, and supplementing Qi and nourishing kidney) in Traditional Chinese Medicine (TCM) on osteoporosis in rats with chronic obstructive pulmonary disease. METHODS: Totally 120 rats were randomly divided into control, model, Bufeijianpi, Bufeiyishen, Yiqizishen, aminophyline groups. Repeated smoke inhalations and bacterial infections were used to duplicate the stable Chronic obstructive pulmonary disease rat model. Normal saline was given to the air control and model groups, while Bufeijianpi granule, Bufeiyishen granule, and Yiqizishen granule, and aminophylline were administrated to rats in the Bufeijianpi, Bufeiyishen, Yiqizishen, and aminophylline groups respectively from weeks 9 through 20. Another 12 weeks without medicines to observe the long-term effect. Rats were sacrificed at week 20 and week 32. Bone mass density (BMD), bone mineral content (BMC), morphology of the femoral head, lung function, and levels of serum interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α were detected. RESULTS: At weeks 20 and 32, tidal volume, peak expiratory flow and expiratory flow at 50% tidal volume in the three TCM-treated groups were higher than those in the model group (P < 0.05). Femur weight, BMD, and BMC were significantly higher in the three TCM-treated groups and the aminophylline-treated group compared with the model group (P < 0.01), except for BMC in the Yiqizishen-treated group at week 20. CONCLUSION: Bufeijianpi, Bufeiyishen, and Yiqizishen granules show good effects in the prevention and treatment of osteoporosis, which can alleviate airflow limitations and inflammation, improve BMD and BMC of the femur, and have favorable long-term effects.

R-value Comprehensive Evaluation Method for Efficacy of Tiao-Bu Fei-Shen Therapies on Cardiac Remodeling of COPD Rats / 世界科学技术-中医药现代化

This study was aimed to evaluate the efficacy of Tiao-Bu Fei-Shen therapies (i.e., Bu-Fei Jian-Pi, Bu-Fei Y i-Shen, Y i-Qi Zi-Shen) on cardiac remodeling of chronic obstructive pulmonary disease (COPD) rats and its mechanisms according to the R-value comprehensive evaluation method. Based on the database of previous experiment of COPD rats, R-value comprehensive evaluation method was used to evaluate the indexes as fellows to discuss efficacy of Tiao-Bu Fei-Shen therapies on cardiac remodeling of COPD rats. ① Indicators of right ventricular morphologic indexes: right ventricular hypertrophy index (RVHI), cardiac muscle sarcomere lengths, bulk density of myocardial mitochondria (Vv), surface area (δ), membrane surface (δm), Vv, δ, δm of heart mitochondria;② Indicators of mechanisms: right ventricular endothelin-1 (ET-1), transforming growth factor-beta ( TGF-β) , vascular endothelial growth factor ( VEGF ) , basic fibroblast growth factor ( bFGF ) , matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). The results showed that the sequence of improving effect of right ventricular remodeling at week 20 was Bu-Fei Jian-Pi, Bu-Fei Y i-Shen, aminophylline, and Y i-Qi Zi-Shen; at week 32 and the integrated week 20 and week 32, the sequence of effect was Bu-Fei Jian-Pi, Bu-Fei Y i-Shen, Y i-Qi Zi-Shen, and aminophylline. At integrated week 20 and week 32, Bu-Fei Jian-Pi had significant better intensity correcting effect than aminophylline (P< 0.01). There was no difference between week 20 and week 32. It showed that each treatment group had good long-term effect. For the mechanism of correcting effect on right ventricular remodeling, at week 20, the sequence of comprehensive effect was Bu-Fei Jian-Pi, Bu-Fei Y i-Shen, aminophylline, and Y i-Qi Zi-Shen. And Bu-Fei Jian-Pi had better effect compared with aminophylline and Y i-Qi Zi-Shen (P< 0.01); Bu-Fei Y i-Shen had better effect than Y i-Qi Zi-Shen (P< 0.05). At week 32, the sequence of effect was Y i-Qi Zi-Shen, aminophylline, Bu-Fei Jian-Pi, and Bu-Fei Y i-Shen. At the integrated week 20 and week 32, the sequence of effect was Bu-Fei Jian-Pi, and Bu-Fei Y i-Shen, Y i-Qi Zi-Shen, and aminophylline. Until week 32, the correcting effect of Tiao-Bu Fei-Shen therapies and aminophylline still maintained the same level as at week 20. It indicated that each treatment plan had good long-term effect. It was concluded that Tiao-Bu Fei-Shen therapies can improve the cardiac remodeling of COPD rats and expression of related factors in the cardiac remodeling through the R-value comprehensive evaluation method. And the effect of Bu-Fei Jian-Pi was obvious with good long-term effect.

Long-term effects of Tiaobu Feishen therapies on systemic and local inflammation responses in rats with stable chronic obstructive pulmonary disease / 中西医结合学报

To evaluate the influence and long-term effects on systemic and local inflammation responses in rat with stable chronic obstructive pulmonary disease (COPD) treated with traditional Chinese medicine (TCM) for regulating and invigorating the lung and kidney, including invigorating the lung and spleen (Bufei Jianpi) therapy, supplementing the lung and kidney (Bufei Yishen) therapy, and nourishing qi and kidney (Yiqi Zishen) therapy.