Tetrahydroisoquinoline alkaloids distributed widely in the nature and some have a broad application in clinic. More attention has been paid in recent years on this type of alkaloid, owing to the diverse range of biological activities exhibited by these alkaloids and the discovery of new functional mechanisms and molecular targets underlying these activities. This article summarized the recent advances in the biological activities and functional mechanism of tetrahydroisoquinoline, which included the activities such as antitumor, antibiotic, antivirus, anti-inflammatory, anticoagulation, bronchodilation, and the action on central nervous system, with the purpose of providing some ideas in the study of biological activity of this type of alkaloid and in the search for lead-compound and rational drug design.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Anticonvulsants ; pharmacology ; Antifungal Agents ; pharmacology ; Antineoplastic Agents ; pharmacology ; Antiviral Agents ; pharmacology ; Bronchodilator Agents ; pharmacology ; Central Nervous System Agents ; pharmacology ; Fibrinolytic Agents ; pharmacology ; Humans ; Neuroprotective Agents ; pharmacology ; Tetrahydroisoquinolines ; chemical synthesis ; chemistry ; pharmacology

OBJECTIVETo compare the bronchofilating and antiallergic effects with piclamilast with ciclamilast, the second-generation phosphodiesterase 4 (PDE4) selective inhibitors.

METHODSEffects of piclamilast and ciclamilast on airway smooth muscle (ASM) at resting tension, carbachol-induced contraction and the synergistic effect of two agents on isoproterenol-induced bronchorelaxation were evaluated in the isolated tracheal strips of guinea pig in a cumulative manner in vitro. Slow reaction substance of anaphylaxis (SRS-A) release from lung tissues of the sensitized guinea pigs after antigen challenge was examined by bioassay. Antiallergic effect of piclamilast, ciclamilast and rolipram on the isolated ASM of sensitized guinea pigs were evaluated with Schultz-Dale reaction.

RESULTSPiclamilast and ciclamilast showed bronchorelaxant effect in ASM at resting tension. EC50 values of piclamilast and ciclamilast were 1.00 x 10(-5) mol/L and 0.84 x 10(-5) mol/L. Piclamilast and ciclamilast could both enhance the bronchodilating effect of isoproterenol in the isolated ASM of guinea pig, reduce the amount of SRS-A released from lung tissues of the sensitized guinea pigs and also inhibit ovalbumin (OA)-induced bronchoconstruction (Schultz-Dale reaction).

CONCLUSIONThe results indicate the bronchodilating effect of ciclamilast is as potent as piclamilast, but the antiallergic effect of ciclamilast is significantly more potent than that of piclamilast.

Animals ; Anti-Allergic Agents ; pharmacology ; Benzamides ; pharmacology ; Bronchodilator Agents ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Guinea Pigs ; In Vitro Techniques ; Isoproterenol ; pharmacology ; Male ; Phosphodiesterase Inhibitors ; pharmacology ; Pyridines ; pharmacology

OBJECTIVE: To determine the extent to which thin-section and volumetric three-dimensional CT can depict airway reactivity to bronchostimulator, and to assess the effect of different airway sizes on the degree of reactivity. MATERIALS AND METHODS: In eight dogs, thin-section CT scans were obtained before and after the administration of methacholine and ventolin. Cross-sectional areas of bronchi at multiple levels, as shown by axial CT, proximal airway volume as revealed by three-dimensional imaging, and peak airway pressure were mea-sured. The significance of airway change induced by methacholine and ventolin, expressed by percentage changes in cross-sectional area, proximal airway volume, and peak airway pressure was statistically evaluated, as was correlation between the degree of airway reactivity and the area of airways. RESULTS: Cross-sectional areas of the bronchi decreased significantly after the administration of methacholine, and scans obtained after a delay of 5 minutes showed that normalization was insufficient. Ventolin induced a significant increase in cross-sectional areas and an increase in proximal airway volume, while the effect of methacholine on the latter was the opposite. Peak airway pres-sure increased after the administration of methacholine, and after a 5-minute delay its level was near that of the control state. Ventolin, however, induced no significant decrease. The degree of airway reactivity did not correlate with airway size. CONCLUSION: Thin-section and volumetric spiral CT with three-dimensional reconstruction can demonstrate airway reactivity to bronchostimulator. The degree of reactivity did not correlate with airway size.
Albuterol/pharmacology ; Animal ; Bronchoconstriction/*physiology ; Bronchoconstrictor Agents/*pharmacology ; Bronchodilator Agents/*pharmacology ; Dogs ; *Imaging, Three-Dimensional ; Methacholine Chloride/pharmacology ; Tomography, X-Ray Computed/*methods

OBJECTIVETo compare the bronchodilating effect of RR-formoterol (RR-FMT) with that of racemic formoterol (rac-FMT) on human bronchus.

METHODSHuman bronchial spiral strips (2 - 4 mm internal diameter,15 mm length) were suspended in tissue baths under resting tension of 1.0 g. The changes of tension induced by RR-FMT and rac-FMT(10 pmol x L(-1) - 3.2 micromol x L(-1)) in a cumulative concentration manner were studied under resting tension conditions or precontraction with carbamylcholine (10 micromol x L(-1)) or histamine(100 micromol x L(-1)) in human bronchus.

RESULTThe bronchodilating effect of RR-FMT was more potent than that of rac-FMT under resting condition(P<0.05). RR-FMT and rac-FMT reversed histamine or carbamylcholine-induced contraction, and the bronchodilating effect of RR-FMT was more potent than that of rac-FMT (P<0.05).

CONCLUSIONThe bronchodilating effect of RR-FMT is more potent than that of rac-FMT in both the resting condition and carbamylcholine or histamine-induced contraction in human bronchus in vitro.

Aged ; Bronchi ; drug effects ; physiology ; Bronchodilator Agents ; pharmacology ; Carbachol ; pharmacology ; Dose-Response Relationship, Drug ; Ethanolamines ; pharmacology ; Formoterol Fumarate ; Histamine ; pharmacology ; Humans ; In Vitro Techniques ; Middle Aged ; Stereoisomerism

This study examined whether propofol and aminophylline affect the mobilization of intracellular calcium in human umbilical vein endothelial cells. Intracellular calcium was measured using laser scanning confocal microscopy. Cultured and serum-starved cells on round coverslips were incubated with propofol or aminophylline for 30 min, and then stimulated with lysophosphatidic acid, propofol and aminophylline. The results were expressed as relative fluorescence intensity and fold stimulation. Propofol decreased the concentration of intracellular calcium, whereas aminophylline caused increased mobilization of intracellular calcium in a concentration-dependent manner. Propofol suppressed the lysophosphatidic acid-induced mobilization of intracellular calcium in a concentration-dependent manner. Propofol further prevented the aminophylline-induced increase of intracellular calcium at clinically relevant concentrations. However, aminophylline reversed the inhibitory effect of propofol on the elevation of intracellular calcium by lysophosphatidic acid. Our results suggest that propofol and aminophylline antagonize each other on the mobilization of intracellular calcium in human umbilical vein endothelial cells at clinically relevant concentrations. Serious consideration should be given to how this interaction affects mobilization of intracellular calcium when these two drugs are used together.
Aminophylline/*antagonists & inhibitors/pharmacology ; Anesthetics, Intravenous/*antagonists & inhibitors/pharmacology ; Bronchodilator Agents/*antagonists & inhibitors/pharmacology ; Calcium/*metabolism ; Cells, Cultured ; Endothelial Cells/*drug effects/metabolism ; Endothelium, Vascular/cytology ; Humans ; Lysophospholipids/pharmacology ; Microscopy, Confocal ; Propofol/*antagonists & inhibitors/pharmacology ; Umbilical Veins/cytology

OBJECTIVETo investigate antimicrobial and bronchodialator effect of hydroalcholic extract of polyherbal drug Shirishadi containing Shirisha (Albezzia lebbeck), Nagarmotha (Cyprus rotandus) & Kantakari (Solanum xanthocarpum).

METHODSAntimicrobial activity was evaluated by disc diffusion method and MIC, MBC, MFC were calculated by micro dilution method. Hydroalcholic extract of this preparation was investigated for its phytochemical analysis, phenol and flavonoid were determined by spectrophotometric method and in vivo bronchodilator effect was analysed by convulsion time.

RESULTSThe phytochemical tests revealed presence of alkaloids, anthraquinones, carbohydrates, flavonoids, saponins and tannins. The antimicrobial result showed the MIC of 6.25 mg/mL against Staphylococcus aureus and 12.5 mg/mL for Escherichia coli and 12.5 mg/mL against remaining bacteria tested, with strong antifungal activity. The maximum inhibition zone is found against Pseudomonas aeruginosa with MIC 16 mg/mL. Drug showed significant bronchodilator effect with 27.86% & 36.13% increase in preconvulsion time of guinea pigs pretreated with 100 & 200 mg/kg body weight of extract.

CONCLUSIONSThe study reveals that the extracts possess antibacterial activity and antifungal activity in a dose dependent manner. This antimicrobial property may be due to presence of several saponins, further studies are highly needed for the drug development.

Albizzia ; chemistry ; Animals ; Anti-Bacterial Agents ; chemistry ; pharmacology ; Bacteria ; drug effects ; Bronchial Spasm ; Bronchodilator Agents ; chemistry ; pharmacology ; Guinea Pigs ; Medicine, Ayurvedic ; Microbial Sensitivity Tests ; Phytotherapy ; Plant Extracts ; chemistry ; pharmacology ; Solanum ; chemistry

OBJECTIVETo determine the inhibitory effects of BIO-1211, a very late antigen-4 (vla-4) antagonist, on bronchoconstriction and neutrophil adhesion in rats.

METHODSFor evaluating ovalbumin-induced bronchoconstriction in the sensitized rats, the changes in lung resistance (RL) and lung dynamic compliance (C(dyn)) were determined after antigen challenge. Neutrophils from the rats were used to determine fibronectin and serum-induced cell adhesion. The effect of BIO-1211 on wheezing was determined after inhalation of histamine and acetylcholine in guinea pigs.

RESULTBIO-1211 aerosol at 1, 3 and 10 mg/ml significantly inhibited the changes in lung resistance and lung dynamic compliance after antigen challenge in the sensitized rats in a dose-dependent manner. BIO-1211 at 25, 50, 100 and 200 microgram/ml inhibited the fibronectin-induced neutrophil adhesion by 23.5%, 24.6%, 61.4% and 58.1%, respectively, and serum-induced adhesion by 29.9%, 35.9%, 35.3% and 15.4%, respectively. Inhalation of 10 mg/ml BIO-1211 did not show any protection against histamine and acetylcholine-induced bronchoconstriction.

CONCLUSIONBIO-1211 inhibits bronchoconstriction and neutrophil adhesion, which may be associated with its effect against bronchoconstriction in rats.

Administration, Inhalation ; Animals ; Asthma ; drug therapy ; physiopathology ; Bronchoconstriction ; drug effects ; physiology ; Bronchodilator Agents ; administration & dosage ; pharmacology ; Cell Adhesion ; drug effects ; Female ; Guinea Pigs ; Male ; Neutrophils ; cytology ; drug effects ; Oligopeptides ; administration & dosage ; pharmacology ; Rats

OBJECTIVETo study the effect of budesonide (BUD) on RORγt expression in the pulmonary tissue of asthmatic mice and mechanisms of BUD in the treatment of asthma.

METHODSBlab/c asthmatic mouse model was induced by ovalbumin (OVA). Thirty female mice were randomly divided into three groups: control, asthmatic and BUD-treated. IL-17 levels in bronchoalveolar lavage fluid (BALF) and serum were measured using ELISA. Total and differential cell counts in BALF were measured. Airway inflammation was evaluated by hematoxylin and eosin staining. IL-17 mRNA and RORγt mRNA expression were measured by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSRORγt mRNA and IL-l7 levels in the asthmatic group were significantly higher than in the control group (P<0.01). BUD treatment significantly decreased RORγt mRNA and IL-l7 levels compared with the asthmatic group (P<0.01). Compared with the control group, total, neutrophil and eosinophil cell count in BALF increased significantly in the asthmatic group (P<0.01). After BUD treatment, counts of total, neutrophil and eosinophil cells in BALF were significantly reduced (P<0.01) and were similar to in the control group. Inflammatory reactions in the respiratory tract were significantly alleviated in the BUD treated group.

CONCLUSIONSRORγt and IL-l7 levels in the pulmonary tissue of asthmatic mice increase and this may be associated with the pathogenesis of asthma. BUD can inhibit RORγt and IL-17 and thus reduces lung inflammation.

Animals ; Asthma ; drug therapy ; metabolism ; Bronchoalveolar Lavage Fluid ; chemistry ; cytology ; Bronchodilator Agents ; pharmacology ; Budesonide ; pharmacology ; Female ; Interleukin-17 ; analysis ; Lung ; metabolism ; pathology ; Mice ; Mice, Inbred BALB C ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; genetics ; RNA, Messenger ; analysis

OBJECTIVETo study the effects of budesonide on hypoxia inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) expression, angiogenesis and airway remodeling in the chronic asthmatic mouse model.

METHODSThirty female BALB/c mice were randomly divided into normal control, asthma model and treatment groups (10 in each group).The asthmatic mouse model was established via OVA challenge test. Mice in the treatment group were administered with aerosol budesonide (100 μg/kg) an hour before the OVA challenge test from the 28th day. Mice in the control group were treated with PBS instead of OVA. Hematoxylin and eosin staining was performed to observe thickness of the airway wall. Masson staining was used for examing collagen deposition of lung tissues. Angiogenesis and HIF-1α and VEGF expression were measured using immunohistochemistry and Western blot. The relationship of airway wall thickness and vessel area to HIF-1α and VEGF expression was investigated.

RESULTSVessel area, collagen deposition of lung tissues and airway wall thickness increased in the asthma model group. Levels of HIF-1α and VEGF were also elevated. Administration of budesonide significantly reduced angiogenesis, collagen deposition of lung tissues and airway wall thickening, as well as expression of HIF-1α and VEGF. The vessel area and airway wall thickness were positively correlated with expression of HIF-1α and VEGF. A positive correlation was also found between the expression of HIF-1α and VEGF.

CONCLUSIONSBudesonide can decease angiogenesis and airway remodeling by inhibiting HIF-1α and VEGF expression in asthmatic mice.

Airway Remodeling ; drug effects ; Animals ; Asthma ; drug therapy ; metabolism ; pathology ; Bronchi ; pathology ; Bronchodilator Agents ; pharmacology ; Budesonide ; pharmacology ; Disease Models, Animal ; Female ; Hypoxia-Inducible Factor 1, alpha Subunit ; analysis ; Mice ; Mice, Inbred BALB C ; Neovascularization, Physiologic ; Vascular Endothelial Growth Factor A ; analysis

OBJECTIVETo observe the changes of the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in acutely isolated alveolar type II (ATII) cells from rats with acute respiratory distress syndrome (ARDS), and test the effects of terbutaline on the cAMP and cGMP levels.

METHODSSD rats were randomized into the control, ARDS, and terbutaline treatment groups, in which the cAMP and cGMP contents in the ATII cells were measured using radioimmunoassay, and the extravascular lung water (EVLW) content was quantified with gravimetric measurement.

RESULTSThe cAMP level in the ATII cells was significantly lowered whereas cGMP level and EVLW content increased in rats with oleic acid-induced ARDS. In terbutaline-treated rats with ARDS, the EVLW content were lower than that of non-treated rats, but still higher than that of the control rats. Terbutaline treatment also increased the content of cAMP but produced no significant effect on cGMP content in the ATII cells of the rats with ARDS.

CONCLUSIONAlveolar fluid clearance rate is decreased in rats with oleic acid-induced ARDS, and terbutaline can improve the capacity of alveolar fluid clearance, the mechanism of which may involve elevated cAMP content in the ATII cells. cAMP and cGMP in ATII cells might participate in the molecular pathogenesis of ARDS.

Acute Disease ; Animals ; Bronchodilator Agents ; pharmacology ; Cyclic AMP ; metabolism ; Cyclic GMP ; metabolism ; Extravascular Lung Water ; metabolism ; Lung Diseases ; chemically induced ; metabolism ; Male ; Oleic Acid ; Pulmonary Alveoli ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Terbutaline ; pharmacology