Uncovering the action mechanism of Shenqi Tiaoshen formula in the treatment of chronic obstructive pulmonary disease through network pharmacology, molecular docking, and experimental verification.

OBJECTIVE: To reveal the potential underlying mechanism of the Shenqi Tiaoshen formula (, SQTS) in the treatment of chronic obstructive pulmonary disease (COPD) by utilizing network pharmacology, molecular docking, and experimental verification. METHODS: Multiple open-source databases and research related to Traditional Chinese Medicine or compounds were employed to screen active ingredients and corresponding potential targets of the SQTS. The protein-protein interaction network screened hub genes, the relevant molecular mechanism and gene regulation were initially identified through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, and molecular docking was used to confirm further the interaction of the main components bound to the core targets. In vivo experiments on the COPD combined Qi-deficiency syndrome rat model were performed to verify the intervention effects and predicted potential molecular mechanisms of the SQTS. RESULTS: This study selected 156 active compounds and 326 candidate targets for treating COPD. Quercetin, Nobiletin, Kaempferol, Luteolin, Ginsenoside Rh2 and Formononetin were probably the main active compounds of SQTS in COPD treatment as they affected the most COPD-related targets, and interleukin-1 (IL-6), signal transducing activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP9), vascular endothelial growth factor A (VEGFA), protein kinase B (AKT1), hypoxia-inducible factor-1α (HIF-1α), and forkhead box O3 (FoxO3) were identified as the hub genes associated with its therapeutic effect. KEGG analysis was mainly enriched in the signaling pathways closely related to inflammation, immunity and oxidative stress, such as HIF-1, tumor necrosis factor (TNF), phosphatidylinositol 3 kinase (PI3K)-AKT, FoxO, apoptosis, IL-17, and toll-like receptor. Molecular docking confirmed that the main active components shared a good affinity with the hub genes. In vivo experiments, the SQTS was found to improve the body weight, exhaustive swimming time, tail-hanging immobility time and struggle times, airway inflammation, lung functions, and inflammatory factors in the rat model of COPD. The up-regulation of p-PI3K, p-AKT, HIF-1α, FoxO3α, toll like receptor 4, VEGFA, Caspase 3, TNF-α, and IL-17 in COPD rats were down-regulated by SQTS, consistent with the network pharmacology results. CONCLUSIONS: This study provides evidence that the SQTS plays a critical role in anti-inflammation via suppressing immune inflammation and oxidative stress related pathways, indicating that the SQTS is a candidate herbal drug for further investigation in treating COPD.

Analysis of chemical components of Shenqi tiaoshen formula / 中国药房

OBJECTIVE To analyze chemical components of Shenqi tiaoshen formula （SQTS）. METHODS UPLC-QE-MS method was adopted. The determination was performed on ACQUITY UPLC BEH C18 column with mobile phase consisted of 0.1% formic acid solution-0.1% formic acid acetonitrile solution （gradient elution） at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃ ， and the sample size was 5 μL. The electrospray ionization source was used to scan positive and negative ions， and the scanning range was m/z 100-1 500. Combined with TCMSP， PubChem and other databases， SQTS active component database was established and the components were identified in combination with relevant literature. RESULTS & CONCLUSIONS Totally 131 chemical components were identified from SQTS， including 23 terpenoids， 22 flavonoids， 21 phenylpropanoids， 12 alkaloids， 11 phenols， 9 amino acid derivatives， 4 fatty acyls， 3 organic acids and others， such as rutin， citrinin， synephrine， cinnamic acid and ginsenoside Rg1，etc. The cracking process of the main components involved the breaking of glycosidic bonds， dehydration， etc.

Establishment and Evaluation of Rat Model for Chronic Obstructive Pulmonary Disease with Lung-spleen Qi Deficiency / 中国实验方剂学杂志

ObjectiveTo establish and evaluate a chronic obstructive pulmonary disease （COPD） model with lung-spleen qi deficiency. MethodA rat model mimicking COPD with lung-spleen qi deficiency was established by the combination of cigarette smoking and intratracheal instillation of lipopolysaccharide （LPS） along with gavage of Sennae Folium infusion. Forty male SPF-grade SD rats were randomly assigned to blank， model， and low- （L-FXY）， medium- （M-FXY）， and high-dose （H-FXY） Sennae Folium infusion groups. Other groups except the blank group were exposed to daily cigarette smoke， with LPS administrated via intratracheal instillation on the 1st and 14th days. On the 28th day of modeling， the L-FXY， M-FXY， and H-FXY groups were administrated with Sennae Folium infusion at 5， 10， and 20 g·kg-1， respectively， and at 4 ℃ for three weeks. The modeling lasted for 49 days. The general conditions （body mass， food intake， fecal water content， and anal temperature） and behaviors （grip strength test and tail suspension test） of rats in different groups were examined. The lung function， lung histopathology， D-xylose， amylase， and gastrin levels in the serum， interleukin（IL）-1β and IL-6 levels in the alveolar lavage fluid， levels of T-lymphocyte subsets （CD4+， CD8+， and CD4+/CD8+） in the peripheral blood， and thymus and spleen indices were measured. ResultTwo rats died in the H-FXY group. Compared with the blank group， both the M-FXY and H-FXY groups exhibited reduced body mass and food intake （P<0.01） and increased fecal water content （P<0.01）. The anal temperature in the H-FXY group was lower than that in the blank group （P<0.01）. The grip strength decreased in the modeling groups compared with the blank group （P<0.01）， and the duration of immobility in the tail suspension test increased in the M-FXY and H-FXY groups （P<0.05， P<0.01）. Compared with the blank group， the modeling groups showed reduced 0.3 second forced expiratory volume （FEV0.3）， FEV0.3/forced vital capacity （FVC）（P<0.01）， thickening of bronchial walls， proliferation of goblet cells， and the presence of emphysematous changes. In terms of gastrointestinal function， the M-FXY and H-FXY groups had lower levels of D-xylose， gastrin， and α-amylase than the blank group （P<0.01）. Regarding the immune and inflammatory indices， the M-FXY and H-FXY groups showed lower thymus and spleen indices than the blank group （P<0.01）. Compared with the blank group， the modeling groups presented lowered CD4+ level （P<0.01） and CD4+/CD8+ ratio （P<0.05， P<0.01） in the peripheral blood and elevated levels of IL-1β and IL-6 in the alveolar lavage fluid （P<0.01） than the blank group. ConclusionA model of COPD with lung-spleen Qi deficiency was established through the combination of daily cigarette smoke， intratracheal instillation with LPS， and gavage of Sennae Folium infusion. The comprehensive evaluation results suggested medium-dose （10 g·kg-1） Sennae Folium infusion for gavage during the modeling of COPD with lung-spleen Qi deficiency.

The role of traditional Chinese medicine characteristic lung rehabilitation for treatment of patients with chronic obstructive pulmonary disease and syndrome of lung and kidney qi deficiency at steady state / 中国中西医结合急救杂志

Objective To observe the clinical effect of traditional Chinese medicine (TCM) characteristic lung rehabilitation in treatment of patients with chronic obstructive pulmonary disease (COPD) and TCM syndrome of lung and kidney qi deficiency at stable period. Methods Sixty patients with stable COPD and lung and kidney qi deficiency syndrome admitted to the First Affiliated Hospital of Anhui University of Chinese Medicine from June to August 2017 were enrolled, and they were divided into routine treatment group and lung rehabilitation treatment group according to the random number table method, each group 30 cases. The routine treatment group was given Seretide (serevent/futicasone) dry powderi nhalation therapy; on the basis of therapy in the routine treatment group, the lung rehabilitation treatment group was treated with TCM characteristic lung rehabilitation technology (acupoint application + Chinese medicine ionic induction + oral administration of Chinese medicine Liuweibuqi granules, delivery at appropriate intervals); both groups were treated for 2 months. The changes of TCM syndrome score, western medicine symptom score, the times of acute exacerbation of COPD, COPD assessment test (CAT) score, lung function indexes: forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC) were observed before and after treatment in two groups. Results After treatment, TCM syndrome score, western medicine symptom score, CAT score, and after treatment the times of acute exacerbation of COPD in both groups were significantly lower than those before treatment, and the above indexes in the lung rehabilitation treatment group were markedly lower than those in routine treatment group [TCM syndrome score:11.93±1.80 vs. 14.27±2.88, western medicine symptom score: 14.20±2.75 vs. 11.93±4.23, CAT score: 14.87±2.60 vs. 16.23±4.39, the times of acute exacerbation of COPD (times): 0.63±0.49 vs. 0.95±0.83, all P < 0.05]. The improvement of FEV1 in the two groups was not significant; but FEV1/FVC in lung rehabilitation treatment group was obviously higher than that before treatment, FEV1/FVC in lung rehabilitation treatment group was significantly higher than that in the routine treatment group [(57.93±7.27)% vs. (52.49±6.61)%, P < 0.05]. Conclusion The application of TCM characteristic lung rehabilitation in the treatment of COPD patients with stable lung and kidney qi deficiency syndrome based on bronchodilators and glucocorticoids can reduce the number of acute exacerbation, improve the patients' clinical symptoms and living quality, but the improvement of lung function is not significant.

Taste from the Matching of Qingyingtang Prescription Features / 浙江中医药大学学报

Objective]To investigate the characteristics of Qingyingtang group side, learning worthy dialectical medication characteristics, to guide clinical practice. [Methods] Retrieve ancient and modern literature, combined with a comprehensive analysis of drug-induced flavor theory;drug potency and taste of Qingyingtang were demolished square analysis, summary described the taste Qingyingtang prescription characteristics. [Results] Analyse Qingyingtang prescriptions from the taste characteristics of compatibility aspects, it can be summarized as follows:salty Hanku vent, Qingreliangxue, Gan Han Zi camp, nourish lung and stomach, bitter cold stasis, blood stasis and new students, Xin Liang Qing Xuan, through heat transfer gas four aspects. Wu Jutong heat into the blood according to the clinical syndrome features, combined with the taste of the above diagnosis and treatment using the compatibility Herbal Prescription for TCM Syndrome methods election due to drug model, called the lead from future generations. [Conclusion] The taste of the theory of the clinical treatment combination prescription medication an important basis for Qingyingtang nature flavor compatibility demolition fomula research can enhance the the world of knowledge and understanding of compatibility, thereby improving clinical scholar ability prescription medication.