The ECM propagates processes in idiopathic pulmonary fibrosis (IPF), leading to progressive lung scarring. We established an IPF-conditioned matrix (IPF-CM) system as a platform for testing drug candidates. Here, we tested the involvement of a PGE2 a...
Phosphodiesterase 4 (PDE4) catalyzes cyclic adenosine monophosphate (cAMP) hydrolysis, playing a crucial role in the cAMP signaling pathway. cAMP is a secondary messenger involved in numerous physiological functions, such as inflammatory responses, i...
Roflumilast is an orally available inhibitor of phosphodiesterase (PDE) type 4, which is widely used in chronic obstructive pulmonary diseases. However, it has low solubility and adverse effects include diarrhea and nausea. Since its solubilization m...
Phosphodiesterase 4B (PDE4B) plays an important role in inflammation. Recently we have reported that roflumilast as a PDE4-selective inhibitor, synergizes with nontypeable Haemophilus influenzae (NTHi) to up-regulate PDE4B expression in vitro and in...
Roflumilast is given as an add-on to inhalation medication in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis. Animal experiments have documented deleterious effects of roflumilast in bacterial infections, but trials...
Traumatic injury remains a critical global health challenge, with polytrauma frequently leading to multi-organ failure and mortality. A severe complication of polytrauma is acute kidney injury (AKI), which is driven by a massive systemic inflammatory...
The failure of axons to regenerate after a spinal cord injury (SCI) remains one of the greatest challenges in neuroscience. The initial mechanical trauma is followed by a secondary injury cascade, creating a hostile microenvironment, which not only i...
The lack of effective anti-fibrotic agents remains a significant unmet need in the treatment of intestinal fibrosis, a condition largely driven by transforming growth factor-β1 (TGF-β1)-mediated myofibroblast activation. Phosphodiesterase 4...
The aim of the present study was to evaluate the possible gut inhibitory role of the phosphodiesterase (PDE) inhibitor roflumilast. Increasing doses of roflumilast were tested against castor oil-induced diarrhea in mice, whereas the pharmacodynamics...
Our desire to live longer has led to an ever-increasing number of novel antiaging products. However, few molecules have any real effect and new ones need to be studied before they can be used commercially. In this contribution, activation of the calo...
Severe infections such as viral, bacterial, or fungal sepsis can cause an inflammatory response in the host, leading to organ failure and septic shock—phosphodiesterase-4 (PDE-4) inhibiting related agents from suppressing cyclic adenosine monop...
Roflumilast is currently administered orally to control acute exacerbations in chronic obstructive pulmonary disease (COPD). However, side effects such as gastrointestinal disturbance and weight loss have limited its application. This work aimed to d...
This study explores developing and optimizing a nanoemulsion (NE) system loaded with dipyridamole and roflumilast, aiming to improve skin penetration and retention. The NE formulation was further transformed into a nanoemulgel to enhance its applicat...
In endothelial cells, high-dose irradiation induces numerous dysfunctions including alteration in junctional proteins such as VE-Cadherin, apoptosis and enhanced adhesiveness linked to overexpression of adhesion molecules like Intercellular Adhesion...
Background/Objectives: Fixed-dose combinations (FDCs) offer significant advantages for patients and healthcare systems by improving adherence and reducing pill burden. However, developing multi-drug formulations remains challenging due to complexitie...
Background: Diffuse large B-cell lymphoma (DLBCL) is a common and often fatal malignancy. The standard-of-care immunochemotherapy, R-CHOP, cures only about 60% of DLBCL patients. Improving this cure rate will likely require the effective translation...
Glucagon-like peptide (GLP)-1 receptor (GLP1R) agonists exert a multitude of beneficial cardiovascular effects beyond control of blood glucose levels and obesity reduction. GLP-1R is a G protein-coupled receptor (GPCR), coupling to adenylyl cyclase (...
Background: Several sarcoidosis patients require treatment with corticosteroids to prevent organ damage and control symptoms. However, corticosteroids are associated with numerous side effects and can be detrimental to patients if used long-term. Rof...
AVRO is an adjunctive four-drug regimen designed to increase the effectiveness of current standard treatment of glioblastoma (GB). AVRO is a repurposed drug regimen consisting of the antinausea drug aprepitant, the antidepressant vortioxetine, the em...
Phosphodiesterase-4 (PDE4) is involved in the synthesis of inflammatory cytokines that mediate several chronic inflammatory disorders, including psoriasis and atopic dermatitis. In recent years, the therapeutic armamentarium in dermatology has expand...
Inhaled bronchodilators and corticosteroids, when indicated, form the backbone of COPD therapy. However, over the last decade there has been an emergence of adjunct therapies in oral or inhaled form that are now part of the therapeutic approach to CO...
Psoriasis is a common chronic immune-mediated disease with many comorbidities and impacts on quality of life. Among the treatments for psoriasis, phosphodiesterase-4 (PDE4) inhibitors are emerging with expanding options. PDE4 inhibitors play a pivota...
The introduction of biologic therapies has led to dramatic improvements in the management of moderate-to-severe psoriasis. Even though the efficacy and safety of the newer biologic agents are difficult to match, oral administration is considered an i...
Highly selective inhibitors of the members of the cAMP-selective cyclic nucleotide phosphodiesterases, or PDE4 family, have shown clinically meaningful activity in two different classes of lung disease: roflumilast in obstructive lung disease, specif...
The development of a wider range of therapeutic options is a key objective in drug discovery for chronic obstructive pulmonary disease (COPD). Fundamental advances in lung biology have the potential to greatly expand the number of therapeutic targets...
Chronic obstructive pulmonary disease (COPD) is a significant disease threatening human health. Currently, roflumilast, a phosphodiesterase (PDE)4 inhibitor, is recommended as a therapeutic agent for COPD. In this study, we investigated the therapeut...
Aralia continentalis has been used in Korea as a folk remedy for arthralgia, rheumatism, and inflammation. However, its anti-lymphoma effect remains uncharacterized. Here, we demonstrate that A. continentalis extract and its three diterpenes efficien...
The analysis of blood samples from mice treated with the PDE4 inhibitor Roflumilast revealed an unexpected reduction in serum potassium levels, while sodium and chloride levels were unaffected. Treatment with several structurally distinct PAN-PDE4 in...
Schistosomiasis is a neglected tropical disease with high morbidity. Recently, the Schistosoma mansoni phosphodiesterase SmPDE4A was suggested as a putative new drug target. To support SmPDE4A targeted drug discovery, we cloned, isolated, and biochem...
Since the early 1980s, phosphodiesterase 4 (PDE4) has been an attractive target for the treatment of inflammation-based diseases. Several scientific advancements, by both academia and pharmaceutical companies, have enabled the identification of many...
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory illness characterized by long-standing respiratory symptoms and airflow limitation. It is a major contributor to respiratory disease-related deaths and currently ranked as the...
Atopic dermatitis (AD) is a chronic inflammatory dermatosis with periods of exacerbation and remissions. AD is characterized by intense, persistent pruritus and heterogeneity in clinical symptomatology and severity. Therapeutic goals include the amel...
Phosphodiesterase 4 (PDE4) is a key enzyme responsible for the hydrolysis of cyclic adenosine monophosphate (cAMP), thereby regulating essential signaling pathways involved in inflammation and immune modulation. Structural studies have demonstrated a...
Self-inflicted violence is a major and growing public health problem and its prediction and prevention is challenging for healthcare systems worldwide. Our aim was to identify prescribed drugs associated with self-directed violent behaviors in Spain....
Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder characterized by immune dysregulation and epidermal barrier dysfunction. Advances in understanding the interplay of genetic predisposition, cytokine signaling, and environmenta...
Background: Seborrheic dermatitis (SD) is a chronic, recurrent inflammatory dermatosis that primarily affects seborrheic areas such as the scalp, face, and upper trunk. Its etiology is multifactorial, involving sebaceous gland activity, immune dysreg...
Background/Objectives: PDE4 is a key regulator of cAMP signaling and a clinically validated anti-inflammatory target; however, the use of PDE4 inhibitors is often limited by adverse effects such as nausea, vomiting, and diarrhea. The natural compound...
Adrenomedullin (ADM) is a vasodilator that causes natriuresis and diuresis. However, the direct effect of ADM on osmotic water permeability in the rat inner medullary collecting duct (IMCD) has not been tested. We investigated whether ADM and its ADM...
Phosphodiesterase (PDE) inhibitors are currently a widespread and extensively studied group of anti-inflammatory and anti-fibrotic compounds which may find use in the treatment of numerous lung diseases, including asthma and chronic obstructive pulmo...
Background: Within the past few years, many new therapies have emerged for psoriasis and psoriatic arthritis (PsA). Current topical therapies—including corticosteroids, vitamin D analogs, tapinarof, and roflumilast—remain the mainstay for...