Artemisia alleviates AGE-induced liver complications via MAPK and RAGE signaling pathways modulation: a combinatorial study

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dc.authoridMOULAHOUM, Hichem/0000-0003-3934-6415
dc.authoridTimur, Suna/0000-0002-1981-7577
dc.authoridZIHNIOGLU, FIGEN/0000-0001-8216-7004
dc.authoridTOK, Kerem/0000-0002-7244-3949
dc.authorscopusid57188963997
dc.authorscopusid57199103659
dc.authorscopusid57679862700
dc.authorscopusid57678944200
dc.authorscopusid6506861131
dc.authorscopusid57220178117
dc.authorscopusid6701638388
dc.authorwosidMOULAHOUM, Hichem/DIC-3335-2022
dc.authorwosidTok, Kerem/AAG-6529-2021
dc.authorwosidTimur, Suna/CAG-0914-2022
dc.contributor.authorMoulahoum, Hichem
dc.contributor.authorGhorbanizamani, Faezeh
dc.contributor.authorKhiari, Zineb
dc.contributor.authorToumi, Mohamed
dc.contributor.authorBenazzoug, Yasmina
dc.contributor.authorTok, Kerem
dc.contributor.authorTimur, Suna
dc.date.accessioned2023-01-12T19:50:45Z
dc.date.available2023-01-12T19:50:45Z
dc.date.issued2022
dc.departmentN/A/Departmenten_US
dc.description.abstractArtemisia herba-alba (AHA) is a traditionally used plant to treat various diseases, including diabetes and metabolic dysfunctions. Plant extracts are generally explored empirically without a deeper assessment of their mechanism of action. Here, we describe a combinatorial study of biochemical, molecular, and bioinformatic (metabolite-protein pharmacology network) analyses to elucidate the mechanism of action of AHA and shed light on its multilevel effects in the treatment of diabetes-related advanced glycation end-products (AGE)-induced liver damages. The extract's polyphenols and flavonoids content were measured and then identified via LC-Q-TOF-MS/MS. Active compounds were used to generate a metabolite-target interaction network via Swiss Target Prediction and other databases. The extract was tested for its antiglycation and aggregation properties. Next, THLE-2 liver cells were challenged with AGEs, and the mechanistic markers were measured [TNF-alpha, IL-6, nitric oxide, total antioxidant capacity, lipid peroxidation (LPO), and caspase 3]. Metabolite and network screening showed the involvement of AHA in diabetes, glycation, liver diseases, aging, and apoptosis. Experimental confirmation showed that AHA inhibited protein modification and AGE formation. Additionally, AHA reduced inflammatory mediators (IL-6, TNF alpha), oxidative stress markers (NO, LPO), and apoptosis (Caspase 3). On the other hand, cellular total antioxidant capacity was restored to normal levels. The combinatorial study showed that AHA regulates AGE-induced liver damages through MAPK-AKT and AGE-RAGE signaling pathways. This report highlights the combination of experimental and network pharmacology for the exact elucidation of AHA mechanism of action as a multitarget option in the therapy of diabetes and AGEs-related diseases.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey-TUBITAK [120Z200]; Projets de Recherche-Formation Universitaire (PRFU) [D01N01UN160420180008]en_US
dc.description.sponsorshipThis project was funded by The Scientific and Technological Research Council of Turkey-TUBITAK (120Z200). The current project was partially funded by the Projets de Recherche-Formation Universitaire (PRFU) (D01N01UN160420180008). EGE MATAL (EGE University) is acknowledged for the LC-Q-TOF-MS/MS analyses and cell culture experiments.en_US
dc.identifier.doi10.1007/s11010-022-04437-w
dc.identifier.endpage2357en_US
dc.identifier.issn0300-8177
dc.identifier.issn1573-4919
dc.identifier.issue10en_US
dc.identifier.pmid35543857en_US
dc.identifier.scopus2-s2.0-85129829742en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage2345en_US
dc.identifier.urihttps://doi.org/10.1007/s11010-022-04437-w
dc.identifier.urihttps://hdl.handle.net/11454/76162
dc.identifier.volume477en_US
dc.identifier.wosWOS:000793625100001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofMolecular and Cellular Biochemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectArtemisia herba-albaen_US
dc.subjectNetwork pharmacologyen_US
dc.subjectDiabetesen_US
dc.subjectAge-related diseasesen_US
dc.subjectAdvanced glycation end-productsen_US
dc.subjectSignaling pathwayen_US
dc.subjectGlycation End-Productsen_US
dc.subjectIn-Vitroen_US
dc.subjectInhibitory-Activityen_US
dc.subjectOxidative Stressen_US
dc.subjectEssential Oilen_US
dc.subjectGrowing Wilden_US
dc.subjectKappa-Ben_US
dc.subjectAntioxidanten_US
dc.subjectGlycotoxinsen_US
dc.subjectApoptosisen_US
dc.titleArtemisia alleviates AGE-induced liver complications via MAPK and RAGE signaling pathways modulation: a combinatorial studyen_US
dc.typeArticleen_US

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