Network pharmacology-based identification of key pharmacological pathways of Yin-Huang-Qing-Fei capsule acting on chronic bronchitis.

For decades in China, the Yin-Huang-Qing-Fei capsule (YHQFC) has been widely used in the treatment of chronic bronchitis, with good curative effects. Owing to the complexity of traditional Chinese herbal formulas, the pharmacological mechanism of YHQFC remains unclear. To address this problem, a network pharmacology-based strategy was proposed in this study. At first, the putative target profile of YHQFC was predicted using MedChem Studio, based on structural and functional similarities of all available YHQFC components to the known drugs obtained from the DrugBank database. Then, an interaction network was constructed using links between putative YHQFC targets and known therapeutic targets of chronic bronchitis. Following the calculation of four topological features (degree, betweenness, closeness, and coreness) of each node in the network, 475 major putative targets of YHQFC and their topological importance were identified. In addition, a pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes pathway database indicated that the major putative targets of YHQFC are significantly associated with various pathways involved in anti-inflammation processes, immune responses, and pathological changes caused by asthma. More interestingly, eight major putative targets of YHQFC (interleukin [IL]-3, IL-4, IL-5, IL-10, IL-13, FCER1G, CCL11, and EPX) were demonstrated to be associated with the inflammatory process that occurs during the progression of asthma. Finally, a molecular docking simulation was performed and the results exhibited that 17 pairs of chemical components and candidate YHQFC targets involved in asthma pathway had strong binding efficiencies. In conclusion, this network pharmacology-based investigation revealed that YHQFC may attenuate the inflammatory reaction of chronic bronchitis by regulating its candidate targets, which may be implicated in the major pathological processes of the asthma pathway.

Metabolic considerations of drugs in the treatment of allergic diseases.

INTRODUCTION: The clinical management of allergic diseases involves a number of drugs, most of which are extensively metabolized. This review aims to analyze the metabolism and the clinical implications of altered metabolism for these drugs. AREAS COVERED: The authors present an overview of current knowledge of the metabolism of: antihistamine drugs, glucocorticoids, inhaled ß-2 bronchodilators, anticholinergics and other drugs used in allergic diseases, such as cromoglycate, omalizumab, montelukast and epinephrine. Polymorphic drug metabolism is relevant for chlorpheniramine, loratadine and montelukast. Inhibition of drug metabolism is relevant for loratadine, methylprednisolone, fluticasone, mometasone, triamcinolone or prednisolone. Polymorphic pre-systemic metabolism may be relevant to budesonide, fluticasone, beclomethasone, mometasone or salmeterol. The authors also discuss the current information on gene variations according to the 1,000 genomes catalog and other databases. Finally, the authors review the clinical implications of these variations with a particular regard to drugs used in the management of allergic diseases. EXPERT OPINION: Most drugs used in allergic diseases are extensively metabolized. Drug interaction or adverse reactions related to altered metabolism are relevant issues that should be considered in the management of allergic diseases. However, much additional research is required before defining pharmacogenomic biomarkers for the management of drugs used in allergic diseases.

Genetic factors in drug metabolism.

Patients vary widely in their response to drugs. Having an understanding of the pharmacokinetic and pharmacodynamic properties of various medications is importantwhen assessing ethnic differences in drug response. Genetic factors can account for 20 to 95 percent of patient variability. Genetic polymorphisms for many drug-metabolizing enzymes and drug targets (e.g., receptors) have been identified. Although currently limited to a few pathways, pharmacogenetic testing may enable physicians to understand why patients react differently to various drugs and to make better decisions about therapy. Ultimately, this understanding may shift the medical paradigm to highly individualized therapeutic regimens.

Taban-Arshan: immunocorrector in atopic bronchial asthma.

Taban-Arshan extract decreased expression of T-lymphocyte activation markers, normalized T-cell-mediated immunity, and suppressed increased activity of natural killer receptors during culturing with lymphocytes of patients with atopic bronchial asthma. Taban-Arshan extract normalized activation processes in the B-cell immunity and stimulated expression of receptors of activation-induced apoptosis.

Design, synthesis, and biological activities of new thieno[3,2-d] pyrimidines as selective type 4 phosphodiesterase inhibitors.

A common pharmacophore for compounds structurally related to nitraquazone has been derived. Using this pharmacophore, new structures have been designed, synthesized, and evaluated for their inhibitory potencies against cyclic adenosine 5'-monophosphate (cAMP) specific phosphodiesterase (PDE 4). From these compounds, 4-benzylamino-2-butylthieno[3,2-d]pyrimidine (4) was selected for optimization. The effects of changes to the lipophilic groups and the amino linkage on the PDE 4 activity have been investigated. As a result, some potent PDE 4 inhibitors, selective with respect to PDE 3, have been identified. A selected group of compounds have been further evaluated for their ability to displace [3H]rolipram from its binding site and also to potentiate isoprenaline-induced cAMP accumulation in isolated guinea pig eosinophils. Of these, 2-butyl-4-cyclohexylaminothieno[3,2-d]pyrimidine (33) has an interesting profile, with an important improvement in PDE 4/[3H]rolipram ratio with respect to reference drugs, and good activity in cAMP potentiation, consistent with efficient cell penetration.