Review
Biochemistry & Molecular Biology
Martin Alexander Schick, Nicolas Schlegel
Summary: Phosphodiesterase 4 inhibitors play an important role in regulating physiological functions and treating diseases, but they also carry significant risks of serious side effects. This review aims to provide a comprehensive overview of the approaches and effects of phosphodiesterase 4 inhibition in different therapeutic applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yung-Fong Tsai, Chun-Yu Chen, I-Wen Lin, Yann-Lii Leu, Shun-Chin Yang, Yu-Ting Syu, Po-Jen Chen, Tsong-Long Hwang
Summary: The research demonstrates that imperatorin inhibits human neutrophil functions by elevating cAMP/PKA, alleviating symptoms in psoriasis models, and potentially serving as a new therapeutic option for neutrophilic psoriasis.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Dermatology
Archie W. Thurston, David W. Osborne, Scott Snyder, Robert C. Higham, Patrick Burnett, David R. Berk
Summary: Topical administration of roflumilast cream 0.3% results in significantly higher concentrations in the skin compared to plasma, indicating a potentially higher efficacy locally. The skin PDE4 inhibition is likely due to roflumilast rather than its active metabolite roflumilast N-oxide.
AMERICAN JOURNAL OF CLINICAL DERMATOLOGY
(2022)
Article
Chemistry, Medicinal
Haobai Liu, Quan Wang, Yue Huang, Jinhui Deng, Xi Xie, Jiaqi Zhu, Yijun Yuan, Yue-Ming He, Yi-You Huang, Hai-Bin Luo, Xixin He
Summary: In this study, a natural derivative of mangostanin called 22d was discovered as a potential novel anti-inflammatory bowel disease (IBD) agent. This compound showed potent inhibition of PDE4 and did not cause any side effects in animal experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Sugin Lal S. Jabaris, V Ranju
Summary: The article summarizes the potential benefits of roflumilast as a supportive drug for COVID-19 pathogenesis, with its anti-inflammatory and immunomodulatory properties that could be beneficial for clinical outcomes in COVID-19 patients.
PULMONARY PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Biology
Abigail Boyd, Peter Lochmaier, Daniel Irelan, Edward Fiedler, Ji Young Lee, Brian Fouty, Lina Abou Saleh, Wito Richter
Summary: Inhibitors of phosphodiesterase 4 (PDE4) reduce serum potassium levels by promoting a transcellular shift of potassium from the blood into cells. This effect is separate from the hypothermic and hypokinetic effects of PDE4 inhibitors. PDE4 inhibitors modulate the adrenergic regulation of cellular potassium uptake.
Article
Clinical Neurology
James Gilleen, Judith Nottage, Farah Yakub, Sarah Kerins, Lorena Valdearenas, Totga Uz, Gez Lahu, Max Tsai, Frank Ogrinc, Steve C. Williams, Dominic Ffytche, Mitut A. Mehta, Sukhi S. Shergill
Summary: This study investigated the potential of the phosphodiesterase-4 inhibitor, roflumilast, to improve neurophysiological deficits in schizophrenia. Results showed that roflumilast at 250 μg significantly enhanced the amplitude of mismatch negativity and working memory-related theta oscillations. This suggests that phosphodiesterase-4 inhibition may act at an intermediate cognitive processing stage.
JOURNAL OF PSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
James Gilleen, Yakub Farah, Cate Davison, Sarah Kerins, Lorena Valdearenas, Tolga Uz, Gez Lahu, Max Tsai, Frank Ogrinc, Avi Reichenberg, Steve C. Williams, Mitul A. Mehta, Sukhi S. Shergill
Summary: The study investigated the potential of using roflumilast to improve cognitive functioning in schizophrenia patients. Results showed that higher doses of roflumilast significantly improved verbal memory, but had no significant impact on working memory.
PSYCHOPHARMACOLOGY
(2021)
Article
Immunology
Jinfeng Xie, Bingtian Bi, Yunyun Qin, Wenli Dong, Jiahong Zhong, Mengfan Li, Yufang Cheng, Jiangping Xu, Haitao Wang
Summary: Inhibition of phosphodiesterase-4 (PDE4) can reduce depressive symptoms and inflammation in mice, showing potential as antidepressant drugs. The down-regulation of HMGB1/RAGE signaling pathway and suppression of inflammasome may contribute to the antidepressant-like effects of PDE4 inhibitors.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Review
Biochemistry & Molecular Biology
Claire Lugnier
Summary: Cyclic nucleotide phosphodiesterases (PDEs) play a crucial role in regulating intracellular cAMP and/or cGMP levels by converting cyclic nucleotides to 5'-nucleotides. Among the PDEs, PDE4 represents the largest family and is involved in various tissues and pathologies. Recent development in PDE4 inhibitors has focused on targeting cardiovascular diseases, obesity, diabetes, and other conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Dermatology
Hanan Rabea Nada, Laila Ahmed Rashed, Jamila Shehada, Pakinam I. N. Mostafa
Summary: This study found that the expression of PDE4 gene is significantly higher in patients with AD compared to controls, and the level of PDE4 mRNA decreases after treatment. This indicates that PDE4 plays a crucial role in the pathogenesis of AD. Targeting PDE4 with inhibitors may revolutionize the treatment of AD.
EUROPEAN JOURNAL OF DERMATOLOGY
(2022)
Article
Chemistry, Medicinal
Jiayuan Liu, Xianglei Zhang, Guofeng Chen, Qiang Shao, Yi Zou, Zhewen Li, Haixia Su, Minjun Li, Yechun Xu
Summary: This study discovered novel drug-like PDE4 inhibitors through high-throughput drug repurposing screening and elucidated their molecular mechanisms of action through crystal structure analysis. It also revealed that CVT-313 is a potent PDE5 inhibitor and led to the discovery of a new inhibitor with improved activity and selectivity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Mitsugi Ookawara, Yasunori Nio, Midori Yamasaki, Kanako Kuniyeda, Guido Hanauer, Kimio Tohyama, Masatoshi Hazama, Takanori Matsuo
Summary: The study identified compound A as a potent and selective PDE4 inhibitor with therapeutic potential for diabetic nephropathy. The compound showed significant effects on glycosylated hemoglobin and urinary albumin/creatinine ratio in DN mouse models, suggesting it may offer a new treatment option with anti-diabetic, anti-fibrotic, and anti-reactive oxygen species effects.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Immunology
Heba A. Farid, Rabab H. Sayed, Marwa El-Sayed El-Shamarka, Omar M. E. Abdel-Salam, Nesrine S. El Sayed
Summary: The study aimed to investigate the neuroprotective role of roflumilast in a rotenone-induced rat model of Parkinson's disease. The results showed that roflumilast improved motor activity and coordination, preserved dopaminergic neurons in the striatum, and activated the PI3K/AKT pathway through the stimulation of multiple signaling cascades. These findings indicate that PDE4 inhibition may be a promising therapeutic approach for Parkinson's disease by activating the PI3K/AKT signaling pathway.
INFLAMMOPHARMACOLOGY
(2023)
Article
Neurosciences
Jessica M. Bonato, Erika Meyer, Patricia S. B. de Mendonca, Humberto Milani, Jos Prickaerts, Rubia Maria Weffort de Oliveira
Summary: The study found that the PDE4 inhibitor roflumilast can alleviate memory loss and neuroinflammation in rats following cerebral ischemia, suggesting a protective effect against the functional sequelae of cerebral ischemia.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)