Effects of Strigolactones on NLRP3 Activation, Nitrosative Stress, and Antioxidant Mox Phenotype: In Vitro and In Silico Evidence

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dc.authoridPrandi, Cristina/0000-0001-9510-8783
dc.authoridSecen, Esma/0009-0002-6421-9776
dc.authoridCinar, Zeynep Ozlem/0000-0002-3553-709X
dc.authoridDonmez, Serhat/0000-0002-6301-7243
dc.contributor.authorAntika, Gizem
dc.contributor.authorCinar, Zeynep Ozlem
dc.contributor.authorDonmez, Serhat
dc.contributor.authorSecen, Esma
dc.contributor.authorOzbil, Mehmet
dc.contributor.authorPrandi, Cristina
dc.contributor.authorTumer, Tugba Boyunegmez
dc.date.accessioned2025-01-27T20:38:59Z
dc.date.available2025-01-27T20:38:59Z
dc.date.issued2024
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractPhytohormones have significant roles in redox metabolism, inflammatory responses, and cellular survival mechanisms within the microenvironment of the mammalian brain. Herein, we identified the mammalian molecular targets of three representative strigolactone (SL) analogues structurally derived from apocarotenoids and the functional equivalent of plant hormones. All tested SL analogues have an inhibitory effect on NLRP3 inflammasome-mediated IL-1 beta release in murine microglial cells. However, IND and EGO10 became prominent among them due to their high potency at low micromolar doses. All SL analogues dose-dependently suppressed the release and expression of proinflammatory factors. For EGO10 and IND, IC50 values for iNOS-associated NO secretion were as low as 1.72 and 1.02 mu M, respectively. In silico analyses revealed that (S)-EGO10 interacted with iNOS, NLRP3, and Keap1 ligands with the highest binding affinities among all stereoisomeric SL analogues. Although all compounds were effective in microglial Mox phenotype polarization, 4-Br-debranone exhibited a differential pattern for upregulating Nrf2-driven downstream enzymes.
dc.description.sponsorshipT?rkiye Bilimsel ve Teknolojik Arastirma Kurumu [218S814]; Scientific and Technological Research Council of Turkey (TUBITAK) [FYL-2021-3564, CA20121]; Canakkale Onsekiz Mart University; COST (European Cooperation in Science and Technology)
dc.description.sponsorshipThis study was partially supported by statutory funds from The Scientific and Technological Research Council of Turkey (TUBITAK; Grant No. 218S814) and Canakkale Onsekiz Mart University (Scientific Research Projects, ID: FYL-2021-3564). This article is based upon work from COST Action CA20121, supported by COST (European Cooperation in Science and Technology) (www.cost.eu) (https://benbedphar.org/about-benbedphar/).
dc.identifier.doi10.1021/acsbiomedchemau.3c00063
dc.identifier.endpage136
dc.identifier.issn2694-2437
dc.identifier.issue3
dc.identifier.pmid38911910
dc.identifier.scopus2-s2.0-85186090722
dc.identifier.scopusqualityQ2
dc.identifier.startpage131
dc.identifier.urihttps://doi.org/10.1021/acsbiomedchemau.3c00063
dc.identifier.urihttps://hdl.handle.net/20.500.12428/23824
dc.identifier.volume4
dc.identifier.wosWOS:001173663300001
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAmer Chemical Soc
dc.relation.ispartofAcs Bio & Med Chem Au
dc.relation.publicationcategoryinfo:eu-repo/semantics/openAccess
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20250125
dc.subjectSL analogues
dc.subjectNLRP3 inflammasome
dc.subjectmicroglialactivation
dc.subjectMox phenotype
dc.subjectNitrosative stress
dc.subjectSIM-A9 cells
dc.titleEffects of Strigolactones on NLRP3 Activation, Nitrosative Stress, and Antioxidant Mox Phenotype: In Vitro and In Silico Evidence
dc.typeArticle

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