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The quest to find novel strategies to tackle respiratory illnesses has led to the exploration of the potential therapeutic effects of carbon monoxide (CO) as an endogenous signaling molecule and a cytoprotective agent. Further, several studies have demonstrated the pharmacological efficacy of CO in animal models of respiratory disorders, such as acute lung injury and pulmonary hypertension. Because of the gaseous nature of CO and its affinity for multiple targets, its controlled delivery has been a challenge. Past studies have employed different delivery modalities, including CO gas, HO-1 inducers, and CO donors, sometimes leading to substantive variations in the resulting pharmacological effects for various reasons. Herein, this review summarizes and analyzes the differences among the profiles of various CO-delivery modalities in terms of their efficacy, dosing regimen, and pharmacokinetics in airways models. We believe that analysis of these issues will help in understanding the fundamental roles of CO in airways, and eventually, contribute to its development as a medicine for respiratory diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Isoquinoline analogs are an important, structurally diverse class of compounds that are extensively used as pharmaceuticals. Derivatives containing the isoquinoline scaffold have become a focus of therapeutic research because of their wide range of biological characteristics. Examples of these drugs, many of which are in clinical application or at the pre-clinical stage, are used to treat a broad swathe of ailments, such as tumors, respiratory diseases, infections, nervous system diseases, cardiovascular and cerebrovascular diseases, endocrine and metabolic diseases., Methods: Data were collected from PubMed, Web of Science, and SciFinder, through searches of drug names., Results: At least 38 isoquinoline-based therapeutic drugs are in clinical application or clinical trials, and their chemical structure and pharmacokinetics are described in detail., Conclusion: The isoquinoline ring is a privileged scaffold which is often preferred as a structural basis for drug design, and plays an important role in drug discovery. This review provides a guide for pharmacologists to find effective preclinical/clinical drugs and examines recent progress in the application of the isoquinoline scaffold., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Flavonoids are an important class of phytopharmaceuticals in plants. Naringin (naringenin- 7-O-rhamnoglucoside) is a flavanone glycoside isolated from folk herbal medicine Exocarpium Citri grandis (called Huajuhong in Chinese). Massive experimental works have been performed on naringin describing its phytochemical, pharmacokinetic, and bioactive properties. Naringin was found to possess multiple pharmacological activities in relieving inflammation, diabetes, neurodegeneration, cardiovascular disorders, and metabolic syndrome. Recently, it has been approved as a potential antitussive and expectorant for clinical trials. However, the pharmacokinetic aspects of naringin and its therapeutic potentials in respiratory diseases have not been comprehensively reviewed. The present review provides highlights of naringin with respect to its absorption, distribution, metabolism, excretion and its therapeutic effects on cough, phlegm, and pulmonary inflammation. This review would be helpful for the interpretation of pharmacokinetics and pharmacodynamics of naringin in clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Rhodiola as one of traditional medicines has been used for clinical treatments due to its strong antioxidant properties. Phytochemical analysis revealed the presence of flavonoids, phenylpropanoids, phenylethanol/benzyl alcohol derivatives, cyanogenic glycosides and terpenoids. The bioactive compounds had been demonstrated to be effective at scavenging reactive oxygen species (ROS). The structures contain phenolic hydroxyl groups and unsaturated bonds. This article reviews antioxidant capacities of the extracts and bioactive components derived from Rhodiola plants. As the major pharmacological ingredient, salidroside is rigorously investigated and used in scientific researches and clinical practices. Accumulated evidences indicated that extracts of Rhodiola plants or salidroside could be able to reverse DNA damage and alter expression of cytokines and antioxidative enzymes induced by ROS. The underlying mechanisms for the antioxidative effects of the herb have been investigated in the last two decades. We summarize the possible effects and acting pathways for the herb involved in several chronic diseases in cardiovascular, respiratory, and nervous systems, as well as potential epigenetic influences. The information generated from experimental and clinical studies offered valuable insights for further investigations of medical potentials of Rhodiola plants., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Asthma, chronic obstructive pulmonary disease, cystic fibrosis, and idiopathic pulmonary fibrosis, are among the most common chronic diseases and their prevalence is increasing. Each of these diseases is characterized by the secretion of cytokines and pro-inflammatory molecules which are thought to play a critical role in their pathogenesis. Moreover, immune cells, particularly neutrophils, macrophages and dendritic cells as well structural cells such as epithelial and airway smooth muscle cells are also involved in the pathogenic cycle of these diseases. There is a pressing need for the development of new therapies for these pulmonary diseases, particularly as no existing treatment has been shown to reduce disease progression. HMGB1 (high-mobility group box 1), originally identified as a nuclear non histone protein with DNA-binding domains can be secreted by living and dying cells and it is now regarded as an important endogenous danger signaling molecule. Besides as a signal of tissue injury, HMGB1 is considered a powerful mediator of inflammation and high levels of HMGB1 are found in chronic lung diseases. The role of HMGB1 in respiratory diseases is still elusive nevertheless these studies suggest an involvement of this cytokine in their pathogenesis. Nucleic acid-based drugs (NABDs) are a novel class of pharmaceuticals including antisense oligonucleotides, DNA-zymes, and RNA interference as mediated by small interfering RNA (siRNA), which are used to dampen the expression of disease-causing genes having therapeutic potential for controlling chronic airway diseases. Due to their inherent difficulties, such as for example sensitivity to endonucleases, their delivery in vivo should be assured by vectors. Non-viral lipid- and polymer-based nanosystems have acquired much importance in this context. In this review, we will discuss these emerging tools in gene therapy of chronic lung diseases, particularly the use of siRNA in the down-regulation of critical molecules in the pathogenesis of chronic lung diseases, with particular emphasis on HMGB1 as therapeutic target., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

There is rapidly growing evidence indicating multiple and important roles of Ca(2+)- permeable cation TRP channels in the airways, both under normal and disease conditions. The aim of this review was to summarize the current knowledge of TRP channels in sensing oxidative, chemical irritant and temperature stimuli by discussing expression and function of several TRP channels in relevant cell types within the respiratory tract, ranging from sensory neurons to airway smooth muscle and epithelial cells. Several of these channels, such as TRPM2, TRPM8, TRPA1 and TRPV1, are discussed in much detail to show that they perform diverse, and often overlapping or contributory, roles in airway hyperreactivity, inflammation, asthma, chronic obstructive pulmonary disease and other respiratory disorders. These include TRPM2 involvement in the disruption of the bronchial epithelial tight junctions during oxidative stress, important roles of TRPA1 and TRPV1 channels in airway inflammation, hyperresponsiveness, chronic cough, and hyperplasia of airway smooth muscles, as well as TRPM8 role in COPD and mucus hypersecretion. Thus, there is increasing evidence that TRP channels not only function as an integral part of the important endogenous protective mechanisms of the respiratory tract capable of detecting and ensuring proper physiological responses to various oxidative, chemical irritant and temperature stimuli, but that altered expression, activation and regulation of these channels may also contribute to the pathogenesis of respiratory diseases.

Breathing is generated and controlled by a brainstem neuronal network. Both intrinsic and synaptic interactions are involved in respiratory rhythm generation and their contribution is state-dependent, changing with hypoxia and the neuromodulatory state. Cellular mechanisms involved in acute or chronic pathological conditions are still unknown. A dysfunction in the neuronal network that controls breathing may be involved in several respiratory disorders such as central sleep apnea, sudden infant death syndrome, congenital hypoventilation, and in some clinical conditions that produce breathing dysfunction such as drug-induced respiratory depression, obesity hypoventilation syndrome, etc. Despite the fact that several drugs are currently used to treat these diseases, the probable effects of this pharmacotherapy on the central rhythm generator and on other neuronal networks related with breathing control is poorly understood. Here, we review the current pharmacological approaches in the treatment of respiratory disorders, such as acetazolamide, theophylline, aminophylline, progesterone, nitric oxide. Possible effects of these drugs on the central respiratory network are discussed and putative therapeutic targets for the development of future pharmacological therapies suggested.