GR24, a synthetic analog of Strigolactones, alleviates inflammation and promotes Nrf2 cytoprotective response: In vitro and in silico evidences

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dc.authoridYılmaz, Yakup Berkay / 0000-0001-8989-8045
dc.authoridTaşkın, Kemal Melih / 0000-0002-3746-0508
dc.authoridTümer, Tuğba / 0000-0002-1740-4867
dc.authoridÖzleyen, Adem / 0000-0003-0195-3383
dc.authoridTASKIN-TOK, Tugba/0000-0002-0064-8400
dc.contributor.authorBoyuneğmez Tümer, Tuğba
dc.contributor.authorYılmaz, Berkay
dc.contributor.authorÖzleyen, Adem
dc.contributor.authorKurt, Begüm
dc.contributor.authorTaşkın Tok, Tuğba
dc.contributor.authorTaşkın, Kemal Melih
dc.contributor.authorSavranoğlu Kulabaş, Seda
dc.date.accessioned2025-01-27T20:47:31Z
dc.date.available2025-01-27T20:47:31Z
dc.date.issued2018
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractNaturally occurring phytohormones have shown distinguished potential in chemoprevention and treatment of chronic inflammatory diseases in mammalian cells. Strigolactones (SLs) are a class of carotenoid-derived lactones regulating many aspects of plant development and recently recognized as phytohormones with promising anticancer activity. In this study, GR24, a synthetic analog and representative of SLs, induced the expression of phase II detoxifying enzymes such as HO-1 and NQO1 in hepatic and macrophage cell lines under normal and inflammatory conditions, respectively. This effect has been found to be mediated by Nrf2 activation. In silico molecular docking against 16-mer peptide binding site on Keapl suggested that GR24 may exert its biological activity by interfering with Keapl and Nrf2 binding. GR24 also displayed remarkably potent inhibitory activity against the production of nitric oxide (NO) and molecular docking analysis on iNOS supported experimental data. Furthermore, GR24 dose dependently suppressed the LPS-induced iNOS expression at both mRNA and protein level. It also significantly decreased IL-1 beta release, mRNA expression of IL-1 beta and COX-2, as well as nuclear accumulation of NF kappa B at the low micro molar range in LPS-stimulated murine macrophages. GR24 promoted AKT activation in insulin resistant skeletal muscle cells and downregulated the expression of enzymes, PEPCK and G6Pase control the rate limiting steps of gluconeogenesis in hepatic cells. The results of molecular docking and ADMET analyses indicated that GR24 might be classified as druggable molecule in drug design. Taken together, all results suggest that SLs can be promising multi-potent botanical leads for the mitigation of inflammatory-mediated chronic disorders.
dc.description.sponsorshipCanakkale Onsekiz Mart University, Canakkale, Turkey [FYL-2017-1339, FBD-2018-1419]
dc.description.sponsorshipBioactivity studies related with the anti-inflammatory part were partially supported by Canakkale Onsekiz Mart University (Scientific Research Projects, Project Numbers: FYL-2017-1339 and FBD-2018-1419), Canakkale, Turkey.
dc.identifier.doi10.1016/j.compbiolchem.2018.07.014
dc.identifier.endpage190
dc.identifier.issn1476-9271
dc.identifier.issn1476-928X
dc.identifier.pmid30048925
dc.identifier.scopus2-s2.0-85050191595
dc.identifier.scopusqualityQ1
dc.identifier.startpage179
dc.identifier.urihttps://doi.org/10.1016/j.compbiolchem.2018.07.014
dc.identifier.urihttps://hdl.handle.net/20.500.12428/24941
dc.identifier.volume76
dc.identifier.wosWOS:000446282500019
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier Sci Ltd
dc.relation.ispartofComputational Biology and Chemistry
dc.relation.publicationcategoryinfo:eu-repo/semantics/openAccess
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20250125
dc.subjectStrigolactones
dc.subjectNrf2
dc.subjectNQO1
dc.subjectHO-1
dc.subjectMolecular docking
dc.titleGR24, a synthetic analog of Strigolactones, alleviates inflammation and promotes Nrf2 cytoprotective response: In vitro and in silico evidences
dc.typeArticle

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