Evidence map›Paper›PMID 38548264›Full record

ArticleJournal of advanced research2024

Ribociclib leverages phosphodiesterase 4 inhibition in the treatment of neutrophilic inflammation and acute respiratory distress syndrome.

Po-Jen Chen, Shun-Hua Chen, Yu-Li Chen, Yi-Hsuan Wang, Cheng-Yu Lin, Chun-Hong Chen, Yung-Fong Tsai, Tsong-Long Hwang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
4.5field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 16 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 6 institutions in 2 countries.

Po-Jen ChenDepartment of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung 824410, Taiwan; Graduate Institute of Medicine, I-Shou University, Kaohsiung 824410, Taiwan.
Shun-Hua ChenDepartmentof Nursing, Fooyin University, Kaohsiung 831301, Taiwan.
Yu-Li ChenResearch Center for Chinese Herbal Medicine and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333324, Taiwan.
Yi-Hsuan WangGraduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333324, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333324, Taiwan.
Cheng-Yu LinDepartment of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.
Chun-Hong ChenDepartment of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung 824410, Taiwan.
Yung-Fong TsaiGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333324, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.
Tsong-Long HwangResearch Center for Chinese Herbal Medicine and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333324, Taiwan; Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333324, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333324, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan. Electronic address: htl@mail.cgust.edu.tw.
Chang Gung University · TWE-Da Hospital · TWChang Gung University of Science and Technology · TWDuke University · USFooyin University · TWMing Chi University of Technology · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionOverwhelming neutrophil activation and oxidative stress significantly contribute to acute respiratory distress syndrome (ARDS) pathogenesis. However, the potential of repurposing ribociclib, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor used clinically in cancer treatment, for treating neutrophilic ARDS remains uncertain. This study illustrated the ability and underlying mechanism of ribociclib for treating ARDS and neutrophilic inflammation.

methodsPrimary human neutrophils were used to determine the therapeutic effects of ribociclib on respiratory bursts, chemotactic responses, and inflammatory signaling. In vitro and silico analyses were performed to determine the underlying molecular mechanisms. The potential of ribociclib repurposing was evaluated using an in vivo ARDS model in lipopolysaccharide (LPS)-primed mice.

resultsWe found that treatment using ribociclib markedly limited overabundant oxidative stress (reactive oxygen species [ROS]) production and chemotactic responses (integrin levels and adhesion) in activated human neutrophils. Ribociclib was also shown to act as a selective inhibitor of phosphodiesterase 4 (PDE4), thereby promoting the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, leading to the inhibition of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) phosphorylation, and calcium influx. Notably, prophylactic administration and post-treatment with ribociclib ameliorated neutrophil infiltration, lung inflammation, accumulation of oxidative stress, pulmonary destruction, and mortality in mice with LPS-induced ARDS.

conclusionWe demonstrated for the first time that ribociclib serves as a novel PDE4 inhibitor for treating neutrophilic inflammation and ARDS. The repurposing ribociclib and targeting neutrophilic PDE4 offer a potential off-label alternative for treating lung lesions and other inflammatory conditions.

Indexed as

AminopyridinesCyclic Nucleotide Phosphodiesterases, Type 4InflammationLipopolysaccharidesNeutrophilsPhosphodiesterase 4 InhibitorsPurinesRespiratory Distress SyndromeAnimalsCyclic AMPDisease Models, AnimalHumansMaleMiceNeutrophil ActivationOxidative StressAminopyridinesCyclic AMPCyclic Nucleotide Phosphodiesterases, Type 4LipopolysaccharidesPhosphodiesterase 4 InhibitorsPurinesReactive Oxygen SpeciesribociclibAcute respiratory distress syndromeNeutrophilic inflammationPhosphodiesterase 4Ribociclib

Identifiers

PMID38548264
PMCPMC11331181
OpenAlexW4393229791

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.