Qufeng Xuanbi Formula Ameliorates Airway Remodeling in Asthmatic Mice by Suppressing Airway Smooth Muscle Cell Proliferation through MEK/ERK Signaling Pathway.

Asthma is a common chronic respiratory disease. The Qufeng Xuanbi formula (QFXBF), a Chinese herbal decoction, has shown efficacy in the management of asthma. The purpose of this study was to investigate the potential therapeutic effects of QFXBF in the treatment of asthma both in vitro and in vivo. Platelet-derived growth factor (PDGF)-induced airway smooth muscle cell (ASMC) proliferation and MTT assays were used to explore the effects of QFXBF on the proliferation of ASMCs. Moreover, 40 female BALB/c mice were randomly divided into five groups: control group, ovalbumin (OVA) group, high QFXBF group, low QFXBF group, and dexamethasone (DEX) group (n = 8 per group). A mouse allergic asthma model was established using the intranasally administered OVA sensitization method. Morphological changes in the lung tissue were examined by hematoxylin and eosin (H&E) staining and Masson's trichrome staining. Finally, the protein expression of alpha-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), phospho-mitogen-activated protein kinase (p-MEK1/2), mitogen-activated protein kinase (MEK1/2), phospho-extracellular signal-regulated kinases (p-ERK1/2), and extracellular signal-regulated kinases (ERK1/2) in ASMCs and lung tissue were determined by western blotting and immunofluorescent staining assays. PDGF significantly increased the viability of ASMCs. Compared with mice in the control group, the airway walls and airway smooth muscle of mice in the OVA group were thickened, and the number of inflammatory cells around the bronchus significantly increased. Moreover, the administration of QFXBF markedly inhibited the proliferation of ASMCs and alleviated the pathological changes induced by OVA. Furthermore, the protein expressions of p-ERK1/2, p-MEK1/2, PCNA, and α-SMA were significantly increased in OVA-treated mice and PDGF-treated ASMCs. Finally, treatment with QFXBF also significantly decreased the protein expression of p-ERK1/2, p-MEK1/2, α-SMA, and PCNA. QFXBF inhibited the proliferation of ASMCs by suppressing MEK/ERK signaling in PDGF-induced ASMCs and OVA-induced mice.

"Yiqi Huayu, Wenyang Lishui" Prescription (YHWLP) Improves the Symptoms of Chronic Obstructive Pulmonary Disease-Induced Chronic Pulmonary Heart Disease by Inhibiting the RhoA/ROCK Signaling Pathway.

BACKGROUND: Chronic pulmonary heart disease (CPHD) is a common type of heart disease. In China, chronic obstructive pulmonary disease (COPD) is one of the main causes of CPHD. At present, there is no specific therapy for COPD-induced CPHD, so it is of great importance to identify a new therapy for CPHD. OBJECTIVE: The purpose of this study was to explore the effects of "Yiqi Huayu, Wenyang Lishui" prescription (YHWLP) on CPHD symptoms. METHODS: Eighty patients with COPD-induced CPHD were randomly divided into the control group and the YHWLP group, both involving treatment for 3 months. Both groups were treated with Western medicine, and the YHWLP group was also treated with YHWLP. The changes (relative to baseline) in the symptoms, pulmonary arterial pressure, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (Fbg), D-dimer (D-D), and ratio of phosphorylated (p)-myosin-binding subunit (MBS)/total (t)-MBS in peripheral blood (which indirectly indicates the activation/inhibition of RhoA/ROCK signaling) were compared between the two groups. RESULTS: YHWLP plus Western medicine was superior to Western medicine alone at reducing symptoms, pulmonary arterial pressure, PT, aPTT, Fbg, D-D, and p-MBS/t-MBS. CONCLUSION: YHWLP can relieve CPHD by inhibiting the RhoA/ROCK signaling pathway, which means YHWLP is a potential treatment for CPHD.

Effect of urban air pollution on CRP and coagulation: a study on inpatients with acute exacerbation of chronic obstructive pulmonary disease.

PURPOSE: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important event in the course of chronic obstructive pulmonary disease that negatively affects patients' quality of life and leads to higher socioeconomic costs. While previous studies have demonstrated a significant association between urban air pollution and hospitalization for AECOPD, there is a lack of research on the impact of particulate matter (PM) on inflammation and coagulation in AECOPD inpatients. Therefore, this study investigated the association of changes in coagulation function and C-reactive protein (CRP) with PM levels in the days preceding hospitalization. PATIENTS AND METHODS: We reviewed the medical records of AECOPD patients admitted to Putuo Hospital, Shanghai University of Traditional Chinese Medicine, between March 2017 and September 2019. We analyzed the association of coagulation function and CRP level in AECOPD patients with PM levels in the days before hospitalization. Multivariate unconditional logistic regression analyses were used to evaluate the adjusted odds ratio (OR) and 95% confidence interval (CI) for the association of CRP data with hospitalization day. Kruskal-Wallis tests were used to evaluate mean aerodynamic diameter of ≥ 2.5 µm (PM2.5) exposure on the day before hospitalization; we assessed its association with changes in prothrombin time (PT) in AECOPD inpatients with different Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes. RESULTS: The peripheral blood PT of AECOPD patients with PM2.5 ≥ 25 mg/L on the day before hospitalization were lower than those of patients with PM2.5 < 25 mg/L (t = 2.052, p = 0.041). Patients with severe GOLD class exposed to greater than 25 mg/L of PM2.5on the day before hospitalization showed significant differences in PT (F = 9.683, p = 0.008). Peripheral blood CRP levels of AECOPD patients exposed to PM2.5 ≥ 25 mg/L and PM10 ≥ 50 mg/L on the day before hospitalization were higher than those of patients exposed to PM2.5 < 25 mg/L and PM10 < 50 mg/L (t = 2.008, p = 0.046; t = 2.637, p = 0.009). Exposure to < 25 mg/L of PM2.5 on the day before hospitalization was significantly associated with CRP levels (adjusted OR 1.91; 95% CI 1.101, 3.315; p = 0.024). CONCLUSION: Exposure of patients with AECOPD to high PM levels on the day before hospitalization was associated with an increased CRP level and shortened PT. Moreover, PM2.5 had a greater effect on CRP level and PT than mean aerodynamic diameter of ≥ 10 µm (PM10). AECOPD patients with severe GOLD class were more sensitive to PM2.5-induced shortening of PT than those with other GOLD classes.

Exploration of the Potential Mechanisms of Compounds from Rheum palmatum L. against Chronic Obstructive Pulmonary Disease: A Network Pharmacology Study.

BACKGROUND: Rheum palmatum L. (RpL) is a traditional Chinese medicine commonly used clinically. However, there was no systematic research to elucidate the mechanisms of RpL acting on COPD. OBJECTIVE: To explore the potential mechanisms against COPD based on network pharmacology. METHODS: The active compounds of RpL were retrieved from TCMSP database, and their corresponding targets were obtained through TCMSP and STITCH databases. COPD-related targets were identified from the TTD, GeneCards and MalaCards database. Drug-disease genes were obtained through intersection analysis, and the correlation between these genes and COPD was analyzed. After that, a protein-protein interaction network was constructed and enrichment analysis was performed. Then, key targets were obtained according to the network topology attributes analysis. Finally, the Auto dock vina 1.1.2 was used for molecular docking to verify the binding ability between the active compounds and key targets. RESULTS: There were 8 active compounds and 90 corresponding targets were identified in RpL. A total of 4502 COPD-related targets were obtained from databases. After cross-analysis, 81 drug-disease targets were obtained. Drug-disease targets mainly regulated apoptosis and inflammatory responses and participated in related signal pathways. Besides, 28 key genes were obtained from the network topology analysis. TP53, TNF, NFKB1, VEGFA, MMP9, and MMP1 were selected to dock with the compounds. The results of molecular docking showed that the above targets have different affinities with the 8 active compounds of RpL. CONCLUSION: The mechanisms of RpL acting on COPD were mainly related to the regulation of apoptosis, inflammatory response, and airway remodeling.

Bufadienolides from Venenum Bufonis Inhibit mTOR-Mediated Cyclin D1 and Retinoblastoma Protein Leading to Arrest of Cell Cycle in Cancer Cells.

OBJECTIVE: Bufadienolides, the main components in Venenum Bufonis secreted from toads, have been proved to be with significant anticancer activity aside from the positive inotropic action as cardenolides. Here an underlying anticancer mechanism was further elucidated for an injection made from Venenum Bufonis containing nine bufadienolides. METHODS: One solution reagent and cell cycle analyses were for determining effect of bufadienolides on cancer cells. Western blotting was used for protein expression. RESULTS: Bufadienolides inhibit cell proliferation and arrest cells in G1 phase. Bufadienolides also inhibit the mammalian target of rapamycin (mTOR) signaling pathway, which is evidenced by the data that bufadienolides inhibit type I insulin-like growth factor- (IGF-1-) activated phosphorylation of mTOR by a concentration- and time-dependent way, as well as phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1). Subsequent results indicated that cyclin D1 expression and phosphorylation of retinoblastoma protein (Rb)-two characterized regulators in cell cycle of G1-are also inhibited and the process is dependent on mTOR pathway. CONCLUSION: Bufadienolides inhibit proliferation partially due to arresting cell cycle in G1 phase, which is mediated by inhibiting mTOR-cyclin D1/Rb signal pathway.

Qu Feng Xuan Bi Formula attenuates anaphylactic rhinitis-asthma symptoms via reducing EOS count and regulating T cell function in rat ARA models.

ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous extract of Qu Feng Xuan Bi Formula (QFXBF, a Chinese herb formula) which composed of Radix Glycyrrhizae, Radix Glycyrrhizae Preparata, Paeonia sterniana Fletcher in Journ, Pheretima, Allium macrostemon Bunge, Astragalus membranaceus (Fisch) Bunge and Divaricate Saposhnikovia Root has been used in treatment of allergic rhinitis and asthma (ARA) as an approved hospital prescription for many years in Jiangsu Province Hospital of Traditional Chinese Medicine, China. The present study was designed to investigate the effect of the aqueous extract of QFXBF in the gene expression of Toll-like receptor 9 (TLR9) and the manners of immune modulation of T cell-associated interleukin (IL-4 and IL-13) in rat ARA models. MATERIALS AND METHODS: Fifty SD male rats were divided into five groups: not treated group, OVA only group (treated only with OVA), dexamethasone (DXM) group, low dose QFXBF group and high dose QFXBF group randomly (n=10 per group). Rat allergic rhinitis and asthma model was developed by ovalbumin (OVA) sensitization and nose infusion. Pathological changes of nasal tissue and lungs were examined by H&E staining. Gene expressions of TLR9, Stat 3, Jak-1 and C-Jun in nasal tissue were assayed by real-time polymerase chain reaction (RT-PCR). The serum and broncho-alveolar lavage fluid (BALF) levels of T cell-associated interleukin (IL-4 and IL-13) were determined by enzyme-linked immunosorbent assay (ELISA). RESULT: The ARA model was successfully established. Marked EOS count was observed in BALF from ARA models. The aqueous extract of QFXBF could reduce EOS levels and increase TLR9 expression, but did not affect the gene expression of Stat-3 and Jak-1 and C-Jun. The reduction of IL-13 concentration in serum from high dose QFXBF group was observed in BALF, albeit not significantly. Despite the not treated group, serum levels of IL-4 had significantly increased in other four groups (P<0.001, n=4-6) but made higher in low dose QFXBF group and DXM group (P<0.05, n=4-6). CONCLUSION: This study originally provides the evidence that the aqueous extract of Qu Feng Xuan Bi Formula alone is effective in the treatment of anaphylactic rhinitis-asthma symptoms. The extract of Qu Feng Xuan Bi Formula was effective to reduce the eosophil recruitment to the lung. In addition it increased the IL-4 concentration in the BALF and expression of TLR9 in the nasal tissue. No alteration was observed in the IL-13 concentration in the BALF and expression of STAT-3, JAK-1 and C-Jun in nasal tissue. The results thereby scientifically provided mechanism of these aqueous extract of QFXBF in improvement of ARA and supported its clinical use.

[Investigation and confirmatory factor analysis of information collected with the four diagnostic methods in patients with bronchial asthma].

OBJECTIVE: To investigate the information acquired through the four diagnostic methods of traditional Chinese medicine in patients with bronchial asthma, and to classify the syndrome types. METHODS: Four hundred and thirty patients with bronchial asthma were randomly investigated. The information acquired through the four diagnostic methods was recorded and the database was established by Amos software, and then the data were analyzed by confirmatory factor analysis (CFA). RESULTS: After analyzing the data with 4 factors, 5 factors and 6 factors, we found that the results of CFA with 6 factors were in accordance with clinical practical experience. CONCLUSION: According to the results of CFA with 6 factors and with the standard regression coefficient 0.4 as primary and secondary critical points, the syndromes in patients with bronchial asthma can be classified into 5 types, which are syndromes of cold fluid retained in lung, phlegm-heat obstructing lung, wind-phlegm blocking lung, qi deficiency of lung and kidney and qi deficiency of spleen.