ABSTRACT
OBJECTIVE: To examine the role and decipher the mechanism of Pingchuan formula (PCF) in treating allergic asthma. METHODS: The mice were treated with saline, dexamethasone (DXM) and PCF for 1 week after the asthma model was established and their respiratory function including respiratory resistance (RI), pulmonary dynamic compliance (Cdyn) and maximum voluntary ventilation (MVV) were measured. In addition, cellular changes in bronchoalveolar lavage fluid (BALF) and pathological changes in lung biopsy as well as the expression level of -smooth muscle actin (α-SMA), transforming growth factor-beta1 (TGF-α1) in BALF and interleukin-5 (IL-5), interleukin-13 (IL-13), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), nuclear factor-kappa B-p65 (NF-κBp65), inhibitor-α of nuclear transcription factor κB (IκBα), p38 mitogen-activated protein kinase (p38MAPK), c-jun n-terminal kinase (JNK) and its phosphorylated proteins in lung tissue were also examined and compared among different groups. RESULTS: Our data suggested that the respiratory functions were significantly improved and the pathological changes ameliorated in the DXM group and the PCF group compared to the model group. Both DXM and PCF effectively decreased the number of eosinophils, lymphocytes, and neutrophils in BAL as well as the secretion of α-SMA and TGF-α1, IL-5, IL-13, while increased the expression of TNF-α and IFN-γ. Furthermore, our study indicated that the NF-κBp65, IκBα, p38MAPK and JNK pathways were inhibited under the treatment of PCF. CONCLUSION: Our data indicated that PCF can attenuate the inflammatory response in asthma through inhibiting the NF-κB/MAPK signaling pathway. This study not only supported the use of PCF in allergic asthma in clinic but also shed light upon afurther understanding of thediseasepathogenesis.
Subject(s)
Asthma , Drugs, Chinese Herbal , MAP Kinase Signaling System , NF-kappa B , Animals , Asthma/drug therapy , Asthma/genetics , Asthma/metabolism , Disease Models, Animal , Mice , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
BACKGROUND/AIMS: Asthma is a common chronic respiratory disease. It has been reported that Pingchuan formula (PCF) can control asthma attacks by reducing airway inflammation, muscle spasm and mucus secretion. However, PCF's mechanism for reducing airway mucus hypersecretion remains unclear. This study aimed to investigate the effect of PCF on airway mucus secretion in asthmatic mice and to explore changes in the PNEC-GABA-IL13-Muc5ac axis. METHODS: Male Babl/c mice were used to establish the asthma model via sensitisation with OVA. Mice were randomly divided into Normal, OVA, DEX, and PCF groups. After treatment, lung histopathology was observed with H&E and PAS staining. BALF levels of IL-5 and IL-13 were detected using ELISA. The levels of mRNA and protein expression for GAD1, GABAARß1, GABAARα1 and Muc5ac in the lung tissue were measured by RT-PCR and Western blot assays. PNECs were observed with AgNOR staining. RESULTS: PCF treatment effectively reduced goblet cell (P < 0.01) and PNEC (P < 0.05) proliferation, lung tissue inflammation and airway mucus hypersecretion. In addition, PCF also markedly downregulated mRNA and protein expression of GAD1, GABAARß1, GABAARα1 and Muc5ac (P < 0.05, compared with OVA), thus inhibiting the GABA-IL-13 pathway in the lung tissue of asthmatic mice. CONCLUSION: These findings suggest that PCF controls asthma attacks by reducing airway inflammation and mucus hypersecretion via the PNEC-GABA-IL13-Muc5ac axis.
Subject(s)
Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Drugs, Chinese Herbal/therapeutic use , Animals , Anti-Asthmatic Agents/pharmacology , Asthma/immunology , Asthma/metabolism , Asthma/pathology , Bronchoalveolar Lavage Fluid/immunology , Cell Proliferation/drug effects , Cytokines/immunology , Drugs, Chinese Herbal/pharmacology , Goblet Cells/drug effects , Interleukin-13/metabolism , Lung/drug effects , Lung/pathology , Male , Mice, Inbred BALB C , Mucin 5AC/metabolism , Mucus/metabolism , Neuroendocrine Cells/drug effects , Receptors, GABA-A/genetics , Receptors, GABA-A/metabolismABSTRACT
BACKGROUND: Asthma, a complex highly prevalent airway disease, is a major public health problem for which current treatment options are inadequate. OBJECTIVE: To evaluate the antiasthma activity of geraniol and investigate its underlying molecular mechanisms. METHODS: In a standard experimental asthma model, Balb/c mice were sensitized with ovalbumin, treated with geraniol (100 or 200 mg/kg) or a vehicle control, during ovalbumin challenge. RESULTS: Treatment of ovalbumin-sensitized/challenged mice with geraniol significantly decreased airway hyperresponsiveness to inhaled methacholine. Geraniol treatment reduced eotaxin levels in bronchoalveolar lavage fluid and attenuated infiltration of eosinophils induced by ovalbumin. Geraniol treatment reduced TH2 cytokines (including interleukins 4, 5, and 13), increased TH1 cytokine interferon γ in bronchoalveolar lavage fluid, and reduced ovalbumin-specific IgE in serum. In addition, treatment of ovalbumin-sensitized/challenged mice with geraniol enhanced T-bet (TH1 response) messenger RNA expression and reduced GATA-3 (TH2 response) messenger RNA expression in lungs. Furthermore, treatment of ovalbumin -sensitized/challenged mice with geraniol further enhanced Nrf2 protein expression and activated Nrf2-directed antioxidant pathways, such as glutamate-cysteine ligase, superoxide dismutase, and glutathione S-transferase, and enhanced formation of reduced glutathione and reduced formation of malondialdehyde in lungs. CONCLUSION: Geraniol attenuated important features of allergic asthma in mice, possibly through the modulation of TH1/TH2 balance and activation the of Nrf2/antioxidant response element pathway.
