Autor segons l'article: Avila-Roman, Javier; Quevedo-Tinoco, Lirenny; Oliveros-Ortiz, Antonio J; Garcia-Gil, Sara; Rodriguez-Garcia, Gabriela; Motilva, Virginia; Gomez-Hurtado, Mario A; Talero, Elena
Departament: Bioquímica i Biotecnologia
Autor/s de la URV: Ávila Román, Francisco Javier
Paraules clau: Chrysin Chrysin-8-<italic>c</italic>-glucoside derivatives Chrysin-8-c-glucoside derivatives Dexamethasone Docking Expressio Flavonoids Ho-1 Inflammatory mediators Keap1 Macrophage Macrophages Nf-kappa-b Nrf2
Resum: Background/Objectives: The beneficial effects of the flavonoid chrysin can be reduced by its poor oral bioavailability. It has been shown that chrysin-8-C-glucoside (1) has a better absorption capability. The aim of this study was to evaluate the antioxidant and anti-inflammatory activity of this glucoside, as well as the respective hexa-acetate derivative 1a and the hexa-ethyl carbonate derivative 1b since the inclusion of moieties in bioactive molecules may increase or modify their biological effects. Methods: THP-1 macrophages were used to determine the viability in the presence of chrysin derivatives, and non-cytotoxic concentrations were selected. Subsequently, lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) production and inflammatory mediators were examined. The involvement of chrysin derivatives with the Keap1 and Nrf2 antioxidant system was determined by docking and Western blotting studies. Results: Our data demonstrated, for the first time, that pretreatment with the three compounds caused a significant reduction in LPS-induced reactive oxygen species (ROS) production and pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) levels, as well as in cyclooxygenase 2 (COX-2) expression. The mechanisms underlying these protective effects were related, at least in part, to the competitive molecular interactions of these phenolic compounds with Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2), which would allow the dissociation of Nrf2 and its translocation into the nucleus and the subsequent up-regulation of hemo-oxygenase 1 (HO-1) expression. Conclusions: Compared to the 8-C-glucoside parent chrysin, compound 1a exhibited the strongest antioxidant and anti-inflammatory activity. We hypothesized that the incorporation of an acetate group (1a) may reduce its polarity and, thus, increase membrane permeability, leading to better pharmacological activity. These findings support the potential use of these phenolic compounds as Nrf2 activators against oxidative-stress-related inflammatory diseases.
Àrees temàtiques: Biodiversidade Biotecnología Chemistry, medicinal Ciências biológicas i Ciências biológicas ii Ciências biológicas iii Drug discovery Farmacia Interdisciplinar Medicina ii Molecular medicine Pharmaceutical science Pharmacology & pharmacy Química Saúde coletiva
Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
Adreça de correu electrònic de l'autor: franciscojavier.avila@urv.cat
Identificador de l'autor: 0000-0001-9766-8178
Data d'alta del registre: 2025-02-19
Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
Referència a l'article segons font original: Pharmaceuticals. 17 (10): 1388-
Referència de l'ítem segons les normes APA: Avila-Roman, Javier; Quevedo-Tinoco, Lirenny; Oliveros-Ortiz, Antonio J; Garcia-Gil, Sara; Rodriguez-Garcia, Gabriela; Motilva, Virginia; Gomez-Hurtad (2024). Synthesis and Bioevaluation of New Stable Derivatives of Chrysin-8-C-Glucoside That Modulate the Antioxidant Keap1/Nrf2/HO-1 Pathway in Human Macrophages. Pharmaceuticals, 17(10), 1388-. DOI: 10.3390/ph17101388
URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
Entitat: Universitat Rovira i Virgili
Any de publicació de la revista: 2024
Tipus de publicació: Journal Publications
Repositori URV