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Novel PDE4 inhibitors derived from Chinese medicine Forsythia

Coon, TA and McKelvey, AC and Weathington, NM and Birru, RL and Lear, T and Leikauf, GD and Chen, BB (2014) Novel PDE4 inhibitors derived from Chinese medicine Forsythia. PLoS ONE, 9 (12).

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Abstract

Cyclic adenosine monophosphate (cAMP) is a crucial intracellular second messenger molecule that converts extracellular molecules to intracellular signal transduction pathways generating cell- and stimulus-specific effects. Importantly, specific phosphodiesterase (PDE) subtypes control the amplitude and duration of cAMP-induced physiological processes and are therefore a prominent pharmacological target currently used in a variety of fields. Here we tested the extracts from traditional Chinese medicine, Forsythia suspense seeds, which have been used for more than 2000 years to relieve respiratory symptoms. Using structural-functional analysis we found its major lignin, Forsynthin, acted as an immunosuppressant by inhibiting PDE4 in inflammatory and immune cell. Moreover, several novel, selective small molecule derivatives of Forsythin were tested in vitro and in murine models of viral and bacterial pneumonia, sepsis and cytokine-driven systemic inflammation. Thus, pharmacological targeting of PDE4 may be a promising strategy for immune-related disorders characterized by amplified host inflammatory response.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Coon, TA
McKelvey, AC
Weathington, NM
Birru, RL
Lear, Ttravislear@pitt.eduTRL340000-0001-9156-0844
Leikauf, GDgleikauf@pitt.eduGLEIKAUF
Chen, BB
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorWu, MinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Vascular Medicine Institute
Date: 30 December 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 12
DOI or Unique Handle: 10.1371/journal.pone.0115937
Schools and Programs: Graduate School of Public Health > Environmental and Occupational Health
Refereed: Yes
Other ID: NLM PMC4280171
PubMed Central ID: PMC4280171
PubMed ID: 25549252
Date Deposited: 12 May 2015 19:40
Last Modified: 30 Mar 2021 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/24079

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