Circadian rhythm is a global phenomenon, the control mechanisms of which are manifested at every level of biological organization, from genes and intracellular mechanisms to networks of cell populations, and to all central neuronal systems at the organismic level. In pharmacotherapy, the pharmacokinetic parameters such as drug absorption and distribution, drug metabolism, and renal elimination show diurnal variations. The symptoms and signs in diseases like asthma, myocardiac infarction, angina pectoris, hypertension and stroke also show diurnal fluctuations. These observations require drug treatment considering the circadian rhythm of body function and disease. Circadian time has to be taken into account as an important variable influencing a drug's pharmacokinetics and/or its effects or side effects in clinical practice.
Absorption ; Angina Pectoris ; Asthma ; Circadian Rhythm ; Clinical Medicine* ; Drug Therapy ; Hypertension ; Infarction ; Metabolism ; Neurons ; Pharmacokinetics ; Stroke

The present study investigated the effect of active components of Descurainia sophia on allergic asthma and explored the underlying mechanism. SD male rats were randomly divided into a normal group(NC), a model group(M), a D. sophia decoction group(DS), a D. sophia fatty oil group(FO), a D. sophia flavonoid glycoside group(FG), a D. sophia oligosaccharide group(Oli), and a positive drug dexamethasone group(Y). The allergic asthma model was induced in rats by intraperitoneal injection of ovalbumin(OVA) and aluminum hydroxide gel adjuvant(sensitization) and atomization of OVA solution(excitation). After modeling, asthma-related indicators, tracheal phenol red excretion, inflammatory cell levels in the peripheral blood, lung permeability index(LPI), and oxygenation index(OI) of rats were detected. The pathological changes of lung tissues were observed by HE staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of inflammatory factors immunoglobulin E(IgE), interleukin-4(IL-4), and interferon-γ(IFN-γ) in the bronchoalveolar lavage fluid(BALF) and the content of endothelin-1(ET-1) and angiotensin-converting enzyme(ACE) in lung tissue homogenate. The serum content of nitric oxide(NO) was detected by colorimetry. Western blot was employed to determine the protein expression of Toll-like receptor 4(TLR4), nuclear factor κB-p65(NF-κB-p65), phosphorylated NF-κB-p65(p-NF-κB-p65), myosin light chain kinase(MLCK), vascular endothelial cadherin(VE cadherin), connexin 43, and claudin 5, and the mechanism of active components of D. sophia on allergic asthma was explored. As revealed by the results, the M group showed extensive infiltration of inflammatory cells around the bronchus of the lung tissues of the allergic asthma rats, thickened bronchial wall, severely deformed alveolar structure, increased number of wheezes, the content of IgE, IL-4, ET-1, and ACE, inflammatory cells, and LPI, and reduced latency of asthma, tracheal phenol red excretion, IFN-γ, NO content, and OI. After the intervention of the active components of D. sophia, the DS, FO, FG, Oli, and Y groups showed improved asthma-related indicators, tracheal phenol red excretion, and lung tissue lesions in allergic asthma rats, and the effects in the FO and Oli groups were superior. The content of inflammatory factors in BALF was recovered in the DS, FO, and Y groups and the FG and Oli groups. The number of inflammatory cells in rats was reduced in the DS and FO groups, and the FG, Oli, and Y groups to varying degrees, and the effect in the FO group was superior. DS, FO, Oli, and Y reduced ET-1, ACE, and LPI and increased NO and OI. FG recovered NO, ET-1, ACE, LPI, and OI to improve lung epithelial damage and permeability. Further investigation of inflammation-related TLR4/NF-κB pathways, MLCK, and related skeleton protein levels showed that TLR4, NF-κB-p65, p-NF-κB-p65, and MLCK levels were increased, and VE cadherin, connexin 43, and claudin 5 were reduced in the M group. DS, FO, FG, Oli, and Y could reduce the protein expression related to the TLR4 pathway to varying degrees, and regulate the protein expression of MLCK, VE cadherin, connexin 43, and claudin 5. It is inferred that the active components of D. sophia improve lung permeability in rats with allergic asthma presumedly by regulating the TLR4/NF-κB signaling pathway to improve airway inflammation, mediating MLCK and connexin, and regulating epithelial damage.
Animals ; Asthma/drug therapy* ; Bronchoalveolar Lavage Fluid ; Inflammation/metabolism* ; Lung ; Male ; Permeability ; Rats

Asthma ; drug therapy ; metabolism ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Inflammation Mediators ; metabolism ; Phytotherapy ; Signal Transduction

OBJECTIVETo discuss the effect of integrated traditional Chinese and Western medicine on Th1/Th2 cytokines level in children with asthma.

METHODChildren with asthma were randomly divided into control group and treatment group. The control group was given Montelukast Sodium tablets for 4 mg (2-5 years old) or 5 mg (6-14 years old), once every night before sleeping. At the same time, the treatment group was given Pingchuan water decoction additionally for one tie per day, in four to six-divided doses for eight weeks. On the other hand, groups of health children were selected as blank control. Before and after treatment, the level of IL-4, IL-13 and IFN-gamma were detected by elisa from 3 mL of venous blood.

RESULTBefore treatment, IL-4 and IL-13 in two groups were obviously higher than healthy group, but IFN-gamma was lower (P < 0.01, P < 0.05). After eight weeks, IL-4 and IL-13 in treatment group went down, but IFN-gamma increased. And there were significant different compared with the control group (P < 0.05).

CONCLUSIONTreating children asthma by integrated traditional Chinese and western medicine can obviously reduce IL4 and IL-13, increase IFN-gamma, and therefore lighten the airway inflammation, prevent asthma attacks effectively.

Adolescent ; Asthma ; drug therapy ; immunology ; metabolism ; Child ; Cytokines ; metabolism ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Th1 Cells ; drug effects ; metabolism ; Th2 Cells ; drug effects ; metabolism ; Western World

OBJECTIVETo study the regulatory effect of San'ao Tang on Thl/Th2 cells and its interference on transcription factor GATA-3 and T-bet-mRNA in asthmatic rats.

METHODRat asthma model was established by abdominal injection and aerosol inhalation of OVA. The content of cytokines IL-4 and IFN-gamma in alveolus lavage fluid of asthmatic rats was detected before and after the oral administration with large, medium, low dose of San'ao Tang and dexamethasone. T-bet and GATA-3 mRNA expressions in lung tissues were determined by RT-PCR.

RESULTCompared with other groups, the medium-dose group showed a notable decrease in IL-4 in rat BALF and an increasing IFN-gamma. Its IL-4/IFN-gamma is significant lower than the asthma group, with expressions of lung tissue GATA-3 and transcription factor T-bet-mRNA in line with changes in IL-4 and IFN-gamma.

CONCLUSIONSan'ao Tang may have a inhibitory effect on airway inflammation of asthmatic rats by regulating Th1/Th2 transfer factors.

Animals ; Asthma ; drug therapy ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Th1 Cells ; drug effects ; metabolism ; Th2 Cells ; drug effects ; metabolism

OBJECTIVEEosinophils play a pivotal role in asthmatic airway inflammation. We previously found a significantly high expression of Slingshot-1L (SSH-1L) in peripheral eosinophils in acute exacerbations of asthma. Objective To investigate the expression and localization patterns of SSH-1L in peripheral blood eosinophils of asthmatic patients and their changes after treatment with inhaled corticosteroids.

METHODSWe recruited 4 outpatients with acute exacerbations of asthma who received no previous corticosteroid treatment and 1 healthy volunteer. From all the subjects 30 ml peripheral venous blood samples were collected before and after a 3-month treatment with inhaled fluticasone. The eosinophils were isolated, purified and counted, and the expressions of SSH-1L in the eosinophils were examined by RT-PCR and Western blotting. The localization of SSH-1L phosphatases in the peripheral eosinophils was detected by immunofluorescence assay in one patient.

RESULTSSSH-1L phosphatases distributed diffusely in the cytoplasm, especially dense near the membrane of the peripheral eosinophils. Glucocorticoids treatment resulted in a significant reduction in both the SSH-1L mRNA expression (0.7403∓0.1124 vs 0.4101∓0.0363, P=0.001) and SSH-1L protein expression (0.3410∓0.1337 vs 0.1543∓0.0551, P=0.039).

CONCLUSIONA high expression of SSH-1L in peripheral eosinophils in acute exacerbations of asthma may play a role in the activation and migration of eosinophils. The efficacy of inhaled corticosteroids in asthma control might be partly attributed to a down-regulated expression of SSH-1L.

Adult ; Aged ; Asthma ; blood ; drug therapy ; Eosinophils ; metabolism ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Male ; Middle Aged ; Phosphoprotein Phosphatases ; metabolism

AIMTo explore the effect of the ginkgo bioba extract on the expression of heme oxygenase-1 (HO-1) in bronchial asthma.

METHODS30 guinea pigs were randomly divided into 3 groups (n = 10): (1) Normal control group; (2) Asthmatic group; (3) Therapeutic group. Blood carbon monoxide Hb (COHb) percent value, Airway resistance and eosinophilic inflammation of airway wall were observed, the expression of HO-1 in lung tissue were observed by immunohistochemical staining.

RESULTSThe expression of HO-1 was mainly located in airway epithelium in these 3 groups, the optical densities were 0.170 +/- 0.020, 0.707 +/- 0.058, 0.397 +/- 0.034, respectively. The asthmatic group showed higher optical densities than that of the normal control group (P < 0.01), and the therapeutic group showed lower optical density than asthmatic group (P < 0.01).

CONCLUSIONThe expression of HO-1 is inhibited significantly by the treatment of the ginkgo bioba extract, which may be one of the mechanism for treating asthma by ginkgo bioba extract.

Animals ; Asthma ; drug therapy ; metabolism ; Ginkgo biloba ; Guinea Pigs ; Heme Oxygenase-1 ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology

P2X7 is the most important subtype of the ATP receptors known so far. Recent investigations showed that the downstream signaling pathway of P2X7 is coupled with several key inflammatory molecules including IL-1beta and IL-18, this suggests P2X7 might have roles in the inflammatory diseases. Moreover, attenuation of P2X7 by selective antagonists in vitro and knockout mice in vivo reducing the inflammatory response indicated that P2X7 is a potential therapeutic target for inflammatory diseases. However, most previous studies on P2X7 were focused on nerve system diseases most, while its effects in inflammatory respiratory diseases, especially in asthma, chronic obstructive pulmonary disease (COPD) and lung cancer have been poorly investigated. In this paper, we reviewed the research progress on the structure, distribution, biological activities of P2X7 and its relationship with inflammatory respiratory diseases including asthma, COPD and lung cancer, along with the development of P2X7 antagonist as therapeutics.
Animals ; Asthma ; drug therapy ; metabolism ; Humans ; Inflammation ; drug therapy ; metabolism ; Interleukin-18 ; metabolism ; Interleukin-1beta ; metabolism ; Lung Neoplasms ; drug therapy ; metabolism ; Mice ; Polymorphism, Single Nucleotide ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; metabolism ; Purinergic P2X Receptor Antagonists ; therapeutic use ; Receptors, Purinergic P2X7 ; chemistry ; genetics ; metabolism ; Respiratory Tract Diseases ; drug therapy ; metabolism

OBJECTIVETo observe the airway inflammatory change in asthmatic rats complicated with chronic obstructive pulmonary disease (COPD) and to assess the intervention effects of Chinese herbs for reinforcing Shen and supplementing qi (CH) on it.

METHODSEighty-four Norway rats were randomized into 7 groups, the normal control group (A), the COPD model group (B), the asthma model group (C), the combined COPD and the asthma model group (D), and the three CH treated groups (E, F and G, combined model rats administered by low-, moderate- and high- dose CH, respectively), 12 rats in each group. Changes of symptoms, pathologic changes of the lung tissue, airway reactivity, and serum levels of interleukin-4, interleukin-6, interleukin-8 (IL-4, IL-6, and IL-8) and interferon-gamma (IFN-gamma) in rats were observed.

RESULTSSymptoms were alleviated in the three CH treated groups. Similar pathological features were shown in group B and D, showing inflammatory cell, mainly lymphocyte, infiltration in bronchial and lung tissues, with cilia denudation, partial alveolar wall rupture, alveolar cavity expansion, and accompanied with evident eosinophilic infiltration. These inflammatory exudation in group E-G was alleviated, while in group C, it developed showing a trend similar to that in group D. Airway resistance raised along with the concentration of Mch used. In group D, the serum level of IL-4 was higher than that in group B, and level of INF-gamma was lower than that in group A, B and C (all P <0.05). CH showed a lowering effect on serum levels of IL-4 and -8, and a dose-dependent rising effect on IFN-gamma.

CONCLUSIONSIL- 4 significantly increased and INF-gamma decreased in rat model of combined COPD and asthma, its mechanism is similar to that of Th1/Th2 imbalance in asthma. Chinese herbs for reinforcing Shen and supplementing qi could improve the symptoms and inhibit the airway inflammation in the combined COPD and asthma model rats, its mechanism might be related with the alleviation of TH1/TH2 imbalance.

Animals ; Asthma ; complications ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Inflammation ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Male ; Phytotherapy ; Pulmonary Disease, Chronic Obstructive ; complications ; drug therapy ; metabolism ; Qi ; Rats ; Rats, Inbred BN

Animals ; Asthma ; drug therapy ; immunology ; metabolism ; physiopathology ; Child, Preschool ; Humans ; Infant ; Leukotrienes ; immunology ; metabolism ; pharmacology ; Respiratory Sounds ; drug effects ; immunology ; physiopathology