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Erschienen in: Inflammopharmacology 2/2024

13.02.2024 | Original Article

Flavipin from fungi as a potential inhibitor of rheumatoid arthritis signaling molecules

verfasst von: Emad A. Ahmed, Abdulaah M. Alzahrani, Salah A. Abdelsalam, Hairul-Islam M. Ibrahim

Erschienen in: Inflammopharmacology | Ausgabe 2/2024

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Abstract

Flavipin, a fungal lower molecular weight biomolecule (MW 196.16 g/mol), has not been yet extensively studied for beneficial preclinical and clinical applications. In recent years, various preclinical mouse models including adjuvant-induced arthritis (AIA) were employed to understand mechanisms associated with Rheumatoid arthritis (RA) and to develop new therapeutic drugs. In the current study, we studied the inhibitory effect of Flavipin on major signaling molecules involved in the inflammatory response during RA using both in-silico virtual interaction and in vivo mouse model of AIA. Our in-silico results clarified that Flavipin interacts with the tumor necrosis factor alpha (TNF-α) through conventional hydrogen binding (H–H) at one of TNF-α critical amino acids tyrosine residues, Tyr119, with binding energy (b.e.) −5.9. In addition, Flavipin binds to ATP-binging sites of the Jesus kinases, JAK1, JAK2 and JAK3, through H–H (b. e. between −5.8 and −6.1) and then it may inhibit JAKs, regulators of RA signaling molecules. Moreover, our molecular dynamics stimulation for the docked TNF-α/Flavipin complex confirmed the specificity and the stability of the interaction. In vitro, Flavipin is not toxic to normal cells at doses below 50 µM (its IC50 in normal fibroblast cell line was above 100 µM). However, in vivo, the arthritis score and hind paw oedema parameters were modulated in Flavipin treated mice. Consistent with the in-silico results the levels of the TNF-α, the nuclear transcription factor kappaB (NF-κB) and the signal transduction and activator of transcription (STAT3, downstream of JAKs) were modulated at joint tissues of the hind-paw of Flavipin/AIA treated mice. Our data suggest Flavipin as a potential therapeutic agent for arthritis can inhibit RA major signaling molecules.
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Metadaten
Titel
Flavipin from fungi as a potential inhibitor of rheumatoid arthritis signaling molecules
verfasst von
Emad A. Ahmed
Abdulaah M. Alzahrani
Salah A. Abdelsalam
Hairul-Islam M. Ibrahim
Publikationsdatum
13.02.2024
Verlag
Springer International Publishing
Erschienen in
Inflammopharmacology / Ausgabe 2/2024
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-024-01429-8

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