Anti-inflammatory effects of naringenin 8-sulphonate from Parinari excelsa Sabine stem bark and its semi-synthetic derivatives

• Type: Article in International Scientific Journal
• Date: 2023

Authors

Macedo, T (Author) Other; Fatima Paiva Martins (Author) FCUP; Ferreres, F (Author) Other; Gomes, NGM (Author) Other; Oliveira, AP (Author) Other; Gil-Izquierdo, A (Author) Other; Araujo, L (Author) Other; Patricia Valentao (Author) FFUP; David M Pereira (Author) FFUP

Journal

Title: Bioorganic Chemistry

Vol. 138

ISSN: 0045-2068

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 2 Citations

Other information

Authenticus ID: P-00Y-M8N

DOI: 10.1016/j.bioorg.2023.106614

Abstract (EN): The inflammatory response is a vital mechanism for repairing damage induced by aberrant health states or external insults; however, persistent activation can be linked to numerous chronic diseases. The nuclear factor kappa beta (NF-kappa B) inflammatory pathway and its associated mediators have emerged as critical targets for ther-apeutic interventions aimed at modulating inflammation, necessitating ongoing drug development. Previous studies have reported the inhibitory effect of a hydroethanol extract derived from Parinari excelsa Sabine (Chrysobalanaceae) on tumour necrosis factor-alpha (TNF-alpha), but the phytoconstituents and mechanisms of action remained elusive. The primary objective of this study was to elucidate the phytochemical composition of P. excelsa stem bark and its role in the mechanisms underpinning its biological activity. Two compounds were detected via HPLC-DAD-ESI(Ion Trap)-MS2 analysis. The predominant compound was isolated and identified as naringenin-8-sulphonate (1), while the identity of the second compound (compound 2) could not be determined. Both compound 1 and the extract were assessed for anti-inflammatory properties using a cell-based inflammation model, in which THP-1-derived macrophages were stimulated with LPS to examine the treatments' effects on various stages of the NF-kappa B pathway. Compound 1, whose biological activity is reported here for the first time, demonstrated inhibition of NF-kappa B activity, reduction in interleukin 6 (IL-6), TNF-alpha, and interleukin 1 beta (IL-1 beta) production, as well as a decrease in p65 nuclear translocation in THP-1 cells, thus highlighting the potential role of sulphur substituents in the activity of naringenin (3). To explore the influence of sulphation on the anti-inflammatory properties of naringenin derivatives, we synthesized naringenin-4 '-O-sulphate (4) and nar-ingenin-7-O-sulphate (5) and evaluated their anti-inflammatory effects. Naringenin derivatives 4 and 5 did not display potent anti-inflammatory activities; however, compound 4 reduced IL-1 beta production, and compound 5 diminished p65 translocation, with both exhibiting the capacity to inhibit TNF-alpha and IL-6 production. Collec-tively, the findings demonstrated that the P. excelsa extract was more efficacious than all tested compounds, while providing insights into the role of sulphation in the anti-inflammatory activity of naringenin derivatives.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11