Inflammation of the asthmatic airway is usually accompanied by increased vascular permeability and plasma exudation. Angiopoietin-1 (Ang1) has potential therapeutic applications in preventing vascular leakage. Recently, we developed a soluble, stable, and potent Ang1 variant, COMP-Ang1. COMP-Ang1 is more potent than native Ang1 in phosphorylating the tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 receptor in lung endothelial cells. We have used a mouse model for allergic airway disease to determine effects of COMP-Ang1 on allergen-induced bronchial inflammation and airway hyper-responsiveness. These mice develop the following typical pathophysiological features of allergic airway disease in the lungs: increased numbers of inflammatory cells of the airways, airway hyper-responsiveness, increased levels of Th2 cell cytokines (IL-4, IL-5, and IL-13), adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), and chemokines (eotaxin and RANTES), and increased vascular permeability. Intravenous administration of COMP-Ang1 reduced bronchial inflammation and airway hyper-responsiveness. In addition, the increased plasma extravasation in allergic airway disease was significantly reduced by the administration of COMP-Ang1. These results suggest that COMP-Ang1 attenuates airway inflammation and hyper-responsiveness, prevents vascular leakage, and may be used as a therapeutic agent in allergic airway disease.
Allergens/immunology ; Angiopoietin-1/genetics/pharmacology/*therapeutic use ; Animals ; Asthma/*prevention & control ; Bronchial Hyperreactivity/physiopathology/prevention & control ; Chemokines/metabolism ; Inflammation/pathology/*prevention & control ; Mice ; Mice, Inbred C57BL ; Recombinant Fusion Proteins/*therapeutic use

OBJECTIVETo observe the effect of compound Chinese herbal monomer (CHM) recipe, consisted of ligustrazin (3.75 mg/kg x d), baicalin (7.5 mg/kg x d) and ginkgolide (2 mg/kg x d), on airway atopic inflammation and hyper-responsiveness in asthma.

METHODSModel guinea pigs of asthma were randomly divided into three groups, the model group, the CHM group and the cromlyn sodium (CS) group, they were treated by atomizing inhalation with normal saline, CHM and CS respectively. The eosinophil count and eosinophil cation protein (ECP) in blood and bronchial alveolar lavage fluid (BALF), and total cell count in BALF were measured and compared. And the effect of treatment on the airway hyperresponsiveness and pathology among groups were compared.

RESULTSCHM showed significant inhibition on blood eosinophil count and BALF and total cell count in BALF, showing significant difference (P < 0.05 or P < 0.01) as compared with those in the model group. The level of ECP was not different in the various groups. Airway responsiveness determination showed that CHM has significant inhibitory action on it. And the pathology of airway inflammation in the CHM group was significantly milder than that in the model group.

CONCLUSIONThe compound inhalation liquid consisted of ligustrazin, baicalin and ginkgolide, has the anti-asthmatic airway atopic inflammation and depression on airway hyper-responsiveness, suggesting that components of compound CHM recipe could inhibit the multiple pathogenetic asthmatic inflammation from different angles and on multiple targets, so as to cure asthma effectively.

Animals ; Anti-Asthmatic Agents ; pharmacology ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Asthma ; drug therapy ; physiopathology ; prevention & control ; Bronchial Hyperreactivity ; drug therapy ; prevention & control ; Bronchoalveolar Lavage Fluid ; cytology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Flavonoids ; pharmacology ; Ginkgo biloba ; Guinea Pigs ; Male ; Pyrazines ; pharmacology ; Random Allocation

BACKGROUND/AIMS: Ozone is an environmentally reactive oxidant, and pycnogenol is a mixture of flavonoid compounds extracted from pine tree bark that have antioxidant activity. We investigated the effects of pycnogenol on reactive nitrogen species, antioxidant responses, and airway responsiveness in BALB/c mice exposed to ozone. METHODS: Antioxidant levels were determined using high performance liquid chromatography with electrochemical detection. Nitric oxide (NO) metabolites in bronchoalveolar lavage (BAL) fluid from BALB/c mice in filtered air and 2 ppm ozone with pycnogenol pretreatment before ozone exposure (n = 6) were quantified colorimetrically using the Griess reaction. RESULTS: Uric acid and ascorbic acid concentrations were significantly higher in BAL fluid following pretreatment with pycnogenol, whereas gamma-tocopherol concentrations were higher in the ozone exposed group but were similar in the ozone and pycnogenol pretreatment groups. Retinol and gamma-tocopherol concentrations tended to increase in the ozone exposure group but were similar in the ozone and pycnogenol pretreatment groups following ozone exposure. Malonylaldehyde concentrations increased in the ozone exposure group but were similar in the ozone and pycnogenol plus ozone groups. The nitrite and total NO metabolite concentrations in BAL fluid, which parallel the in vivo generation of NO in the airways, were significantly greater in the ozone exposed group than the group exposed to filtered air, but decreased with pycnogenol pretreatment. CONCLUSIONS: Pycnogenol may increase levels of antioxidant enzymes and decrease levels of nitrogen species, suggesting that antioxidants minimize the effects of acute ozone exposure via a protective mechanism.
Animals ; Antioxidants/*pharmacology ; Ascorbic Acid/metabolism ; Bronchial Hyperreactivity/chemically induced/metabolism/*prevention & control ; Bronchoalveolar Lavage Fluid/chemistry ; Bronchoconstriction/drug effects ; Disease Models, Animal ; Female ; Flavonoids/*pharmacology ; Inhalation Exposure ; Lung/*drug effects/enzymology/physiopathology ; Malondialdehyde/metabolism ; Mice ; Mice, Inbred BALB C ; Nitric Oxide/metabolism ; Oxidative Stress/*drug effects ; *Ozone ; Uric Acid/metabolism ; Vitamin A/metabolism ; alpha-Tocopherol/metabolism